Four weeks of off-treatment follow-up is sufficient to determine virologic responses at off-treatment week 12 in patients with hepatitis C virus infection receiving pangenotypic direct-acting antivirals

Four weeks of off-treatment follow-up is sufficient to determine virologic responses at off-treatment week 12 in patients with hepatitis C virus infection receiving pangenotypic direct-acting antivirals | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Four weeks of off-treatment follow-up is sufficient to determine virologic responses at off-treatment week 12 in patients with hepatitis C virus infection receiving pangenotypic direct-acting antivirals Chen-Hua Liu, Yu-Ping Chang, Ji-Yuh Lee, Chi-Yi Chen, Wei-Yu Kao, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3876749/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Apr, 2024 Read the published version in Journal of Medical Virology → Version 1 posted You are reading this latest preprint version Abstract Background: Early confirmation of sustained virologic response (SVR) or viral relapse after direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow-ups. Methods: A total of 1011 patients who achieved end-of-treatment virologic response, including 526 receiving pangenotypic DAAs, and 485 receiving genotype-specific DAAs, who had available off-treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off-treatment week 12 (SVR 12 ) or viral relapse were included in the analysis. The positive predictive value (PPV) and negative predictive value (NPV) of SVR 4 to predict patients with SVR 12 or viral relapse were reported. Furthermore, we analyzed the concordance rate between SVR 12 and SVR 24 in 943 patients with available SVR 24 data. Results: The PPV and NPV of SVR 4 to predict SVR 12 were 98.5% (95% confidence interval [CI]: 98.0%-98.9%) and 100% (95% CI: 66.4%-100%) in the entire population. The PPV of SVR 4 to predict SVR 12 in patients receiving pangenotypic DAAs was higher than those receiving genotype-specific DAAs (99.8% [95% CI: 98.9%-100%] versus 97.1% [95% CI: 96.2%-97.8%], p < 0.001). The NPVs of SVR 4 to predict viral relapse were 100%, regardless of type of DAAs. Moreover, the concordance rate between SVR 12 and SVR 24 was 100%. Conclusion: In patients with HCV who are treated with pangenotypic DAAs, an off-treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off-treatment week 12. hepatitis C virus sustained virologic response relapse direct-acting antiviral pangenotypic genotype-specific sofosbuvir velpatasvir glecaprevir pibrentasvir Figures Figure 1 Introduction The management of hepatitis C virus (HCV) infection has undergone a paradigm shift since the advent of direct-acting antivirals (DAAs). 1 With the rapid evolution of new DAA regimens, the fixed-dose combination (FDC) of pangenotypic DAAs, including sofosbuvir/velpatasvir (SOF/VEL), glecaprevir/pibrentasvir (GLE/PIB), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX), are now recommended by the professional societies as the primary treatment agents for HCV due to their ease of use, high potency, and excellent safety profiles. 2–10 This remarkable achievement has prompted the World Health Organization (WHO) in 2015 to set a target for HCV elimination by 2030, which includes achieving 90% diagnosis, an 80% of treatment uptake, and a 65% reduction in mortality, all aiming to combat the adverse health consequences associated with HCV. In the era when interferon (IFN) was the primary treatment for HCV, the key indicator for successfully viral eradication was the sustained virologic response (SVR), often assessed at off-treatment week 24. Two pivotal studies have shown that achieving SVR at off-therapy week 12 (SVR 12 ) following peginterferon (PEG-IFN) plus ribavirin (RBV) predicted SVR 24 in 98–99.7%. 11,12 Additionally, the positive predictive value (PPV) of SVR 4 in forecasting SVR 24 was 96%. 12 On the other way, patients experiencing viral relapse at off-treatment week 24 typically exhibited detectable viremia earlier, between off-treatment weeks 4 to 8. 11 Subsequent pooled analyses of various clinical trials and drug development programs involving PEG-IFN plus RBV, albinterferon (ALB-IFN) plus RBV, as well as the first-generation DAAs, telaprevir (TVR) and boceprevir (BOC), in combination with PEG-IFN plus RBV, demonstrated excellent concordance rates between SVR 12 and SVR 24 , ranging from 98.3–100%.. 13 However, the ability of SVR 4 to predict SVR 24 was found to be suboptimal for HCV genotype 1 and genotype 2/3 infections, with PPVs of 91.1% and 93.3%, respectively. Following the widespread adoption of IFN-free DAAs post-2013, Yoshida et al. conducted an evaluation involving 863 patients with HCV genotype 1 to 6 infections treated with sofosbuvir (SOF) plus RBV with or without PEG-IFN combination. 14 Their study found a 100% concordance rate between SVR 12 and SVR 24 for patients with HCV genotype 1, 4, and 6 infections receiving SOF plus PEG-IFN/RBV. For those with genotype 2 and 3 infections receiving SOF plus RBV, the rates were 100% and 99.1%, respectively. Notably, the PPVs of SVR 4 for predicting SVR 12 ranged from 97.7–98.0%, surpassing the PPVs of SVR 4 for patients receiving PEG-IFN plus RBV. Furthermore, the negative predictive values (NPVs) of SVR 4 to predict SVR 12 , and of SVR 12 to predict SVR 24 , were both 100%. In a separate study by Sulkowski et al., evaluating patients treated with the pangenotypic sofosbuvir/velpatasvir (SOF/VEL) in the ASTRAL phase III program, the PPVs of SVR 4 to predict SVR 12 and SVR 12 to predict SVR 24 were 99.7% and 100%, respectively. Additionally, both SVR 4 and SVR 12 demonstrated 100% NPVs in predicting viral relapse at off-treatment weeks 12 and 24. 15 The reports from clinical trials indicate an increasing trend in the PPV of achieving SVR 4 to predict the likelihood of achieving SVR 12 , particularly as treatments have shifted from IFN-based therapies to DAAs. However, there's a lack of real-world data assessing the clinical relevance of SVR 4 in predicting SVR 12 among patients receiving both pangenotypic and genotype-specific DAAs. Given that the SVR 12 rates often exceed 95% with short courses of pangenotypic DAAs, this holds significant importance from a public health perspective, especially for patients who might be at risk of not adhering to off-treatment follow-ups. Therefore, our aim was to evaluate and compare how effectively SVR 4 predicted SVR 12 in patients treated with both pangenotypic and genotype-specific DAAs for HCV. These results may make healthcare providers assess the treatment responses earlier in daily clinical practice. Materials and Methods Patients Between January 2015 and December 2023, individuals aged 18 or older who achieved undetectable levels of HCV ribonucleic acid (RNA) (Cobas TaqMan HCV Test v2.0, Roche Diagnostics GmbH, Mannheim, Germany, lower limit of quantification [LLOQ]: 15 IU/mL) at the end of treatment, following a regimen of 8 to 24 weeks of IFN-free DAAs for HCV infection, were retrospectively enrolled at 11 academic centers in Taiwan. Participants were confirmed to have HCV infection if they tested positive for quantifiable serum HCV RNA levels. Following the achievement of an end-of-treatment virologic response, these patients underwent serum HCV RNA testing at off-treatment weeks 4, 12, and 24. The study's treatment outcomes were categorized into SVR 12 , viral relapse (defined as detectable serum HCV RNA at off-treatment week 12 with the same HCV genotype/subtype or strains as pretreatment), and reinfection (defined as detectable serum HCV RNA at off-treatment week 12 with a different HCV genotype/subtype or strains compared to pretreatment). 16 The primary endpoint of the study analyzed the diagnostic accuracy of serum HCV RNA level at off-treatment week 4 to predict patients who achieved SVR 12 or experienced viral relapse at off-treatment week 12. Patients were excluded from the primary analysis if they were diagnosed with reinfection, lacked available pretreatment HCV genotyping (Roche Cobas HCV GT, Roche Diagnostics GmbH, Mannheim, Germany, or Abbott RealTi me HCV Genotype II, Abbott Laboratories, Abbott Park, Illinois, USA), or did not undergo serum HCV RNA testing at off-treatment weeks 4 and 12. 17 Among patients who were confirmed to have achieved SVR 12 and those who experienced viral relapse at off-treatment week 12, the secondary endpoint was to evaluate the diagnostic accuracy of serum HCV RNA level at off-treatment week 12 in predicting patients who would attain either SVR 24 or viral relapse at off-treatment week 24. Patients who were reinfected with HCV at off-treatment week 24 or lacked available serum HCV RNA testing at off-treatment week 24 were excluded from the secondary analysis. The study received approval from the Research Ethics Committee of each participating center, and was conducted in accordance with ethical principles, and the guidelines outlined in the Declaration of Helsinki. Study Design Pretreatment demographic information, encompassing age, sex, hepatitis B virus (HBV) coinfection, identified as the presence of HBV surface antigen (HBsAg) (Abbott Architect HBsAg qualitative assay, Abbott Laboratories, Abbott Park, Illinois, USA), human immunodeficiency virus (HIV) coinfection, identified as the presence of HIV antibody (anti-HIV) (Abbott Architect HIV Ag/Ab Combo, Abbott Laboratories), presence of decompensated cirrhosis, end-stage kidney disease (ESKD) or solid organ transplantation, a history of hepatocellular carcinoma (HCC), serum HCV RNA level and genotype/subtype, DAA regimen, treatment duration, the stage of hepatic fibrosis assessed through liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) ((FibroScan®, Echosens, Paris, France), and fibrosis index based on four parameters (FIB-4) were all evaluated. 17.18 Additionally, data were collected for serum HCV RNA levels at the end of treatment, as well as at off-treatment weeks 4, 12, and 24. For patients with detectable HCV RNA levels at off-treatment weeks 12 and 24, information regarding HCV genotyping and direct sequencing of the HCV genome with phylogenetic analysis was assessed when available to confirm relapse or reinfection. The pangenotypic DAA regimens encompassed SOF/VEL, GLE/PIB, and SOF/VEL/VOX, while the genotype-specific DAA regimens included sofosbuvir/ledipasvir (SOF/LDV), SOF plus daclatasvir (DCV), SOF plus RBV, paritaprevir/ritonavir/ombitasvir plus dasabuvir (PrOD), and elbasvir/grazoprevir (EBR/GZR). The cut-off values used for LSM to categorize fibrosis stages were as follows: ≤ 7.0 kilopascals (kPa) for F0-F1, 7.1–9.4 kPa for F2, 9.5–12.4 kPa for F3, and ≥ 12.5 kPa for F4. 19 Statistical Analysis The statistical analyses were conducted using IBM's SPSS Statistics Version 26.0. Pretreatment characteristics were presented as numbers (percentages) for categorical variables. A comparison between patients receiving pangenotypic and genotype-specific DAAs was performed using the chi-squared test. The sensitivity, specificity, PPV, NPV, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) with 95% confidence intervals (CI) of SVR 4 to predict SVR 12 in the entire population and among those receiving pangenotypic and genotype-specific DAAs were calculated and presented. Additionally, the same parameters were used to describe the concordance between SVR 12 and SVR 24 . Among patients who achieved SVR 4 , univariate logistic regression analysis was employed to assess factors associated with the concordance or discordance for SVR 12 . Results were presented as odds ratios (OR) with 95% CI. Subsequently, multivariate analysis was conducted to identify independent factors associated with the concordance of SVR 4 and SVR 12 for variables with a p-value less than 0.10 in the univariate analysis. All statistical analyses were two-tailed, and the statistical significance was defined as a p-value less than 0.05. Results Patient Characteristics Among 1051 patients who achieved an end-of-treatment virologic response using IFN-free DAAs for HCV, 40 were excluded from the study due to a lack of off-treatment week 4 (n = 11) and off-treatment week 12 (n = 28) HCV RNA testing, and HCV reinfection (n = 1). Subsequently, the remaining 1011 patients were included in the primary endpoint analysis. Among them, 987 achieved SVR 12 , while 24 experienced viral relapse. For the secondary endpoint analysis, 943 out of the 1011 patients from the primary analysis were included. This exclusion accounted for 68 patients due to a lack of off-treatment week 24 HCV RNA testing (n = 65) and HCV reinfection (n = 3) (Fig. 1 ). Among the four cases of HCV reinfection, three demonstrated HCV genotype/subtype switches, while the remaining one patient with HCV genotype 1b infection both pretreatment and at the time of reinfection at off-treatment week 24 was confirmed to have HCV reinfection through direct sequencing and phylogenetic mapping. All individuals experiencing viral relapse exhibited the same HCV genotype/subtype between pretreatment and the time of viral relapse, as determined by commercial HCV genotyping without additional direct sequencing and phylogenetic mapping. In the baseline characteristics, 526 patients (52.0%) received pangenotypic DAAs, while 485 (48.0%) were treated with genotype-specific DAAs. Those receiving pangenotypic DAAs showed a higher percentage of males, HBV and HIV coinfection, decompensated cirrhosis, HCV RNA levels > 2,000,000 IU/mL, shorter treatment duration, SVR 12 rate, and F0-F1 hepatic fibrosis compared to those receiving genotype-specific DAAs. Conversely, patients treated with genotype-specific DAAs had a higher percentage of individuals over the age of 50, ESKD, a history of HCC, HCV genotype 1 infection, and a FIB-4 score > 3.25 (Table 1 ). Table 1 Baseline characteristics Characteristics, n (%) Overall (N = 1011) Pangenotypic DAAs (n = 526) Genotype-specific DAAs (n = 485) p value * Age > 50 years 716 (70.8) 324 (61.2) 392 (80.8) < 0.001 Male 570 (56.4) 322 (61.2) 248 (51.1) 0.001 HBV coinfection 65 (6.4) 42 (8.0) 23 (4.7) 0.04 HIV coinfection 165 (16.3) 134 (25.5) 31 (6.4) < 0.001 Decompensated cirrhosis 48 (4.7) 41 (7.8) 7 (1.4) < 0.001 ESKD 161 (15.9) 54 (10.3) 107 (22.1) 2,000,000 IU/mL 469 (46.4) 269 (51.1) 200 (41.2) 0.002 HCV genotype < 0.001 1 † 7 (0.7) 7 (1.3) 0 (0) 1a 45 (4.5) 26 (4.9) 19 (3.9) 1b 548 (54.2) 170 (32.3) 378 (77.9) 2 321 (31.8) 241 (45.8) 80 (16.5) 3 12 (1.2) 11 (2.1) 1 (0.2) 4 1 (0.1) 1 (0.2) 0 (0) 6 60 (5.9) 54 (10.3) 6 (1.2) Others ‡ 17 (1.7) 16 (1.3) 1 (0.2) DAA regimen < 0.001 GLE/PIB 133 (13.1) 133 (25.3) 0 (0) SOF/VEL 378 (37.4) 378 (71.9) 0 (0) SOF/VEL/VOX 15 (1.5) 15 (2.8) 0 (0) PrOD 191 (18.9) 0 (0) 191 (39.4) EBR/GZR 62 (6.1) 0 (0) 62 (12.8) SOF plus RBV 21 (2.1) 0 (0) 21 (4.3) SOF/LDV 167 (16.5) 0 (0) 167 (34.4) SOF plus DCV 44 (4.4) 0 (0) 44 (9.1) Treatment duration, week < 0.001 8 115 (11.4) 110 (20.9) 5 (1.0) 12 862 (85.3) 389 (74.0) 473 (97.5) 24 34 (3.4) 27 (5.1) 7 (1.4) Treatment outcome 0.003 SVR 12 987 (97.6) 521 (99.0) 466 (96.1) Relapse 24 (2.4) 5 (1.0) 19 (3.9) Fibrosis stage (METAVIR) § 3.25, n (%) 315 (31.2) 110 (20.9) 205 (42.3) < 0.001 DAA, direct-acting antiviral; HBV, hepatitis B virus; HIV, human immunodeficiency virus; ESKD, end-stage kidney disease; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; RNA, ribonucleic acid; IU, international unit; GLE/PIB, glecaprevir/pibrentasvir; SOF/VEL, sofosbuvir/velpatasvir; SOF/VEL/VOX, sofosbuvir/velpatasvir/voxilaprevir; PrOD, paritaprevir/ritonavir/ombitasvir plus dasabuvir; EBR/GZR, elbasvir/grazoprevir; RBV, ribavirin; SOF/LDV, sofosbuvir/ledipasvir; DCV, daclatasvir; SVR 12 , sustained virologic response at off-treatment week 12; FIB-4, fibrosis index based on four parameters. * Pangenotypic DAA group versus genotype-specific DAA group, using chi-square tests. † Unsubtypable genotype 1 infection. ‡ Including mixed genotype infection, and invalid genotyping. § Assessing liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE). The cut-off values of LSM for a hepatic fibrosis stage of F0-1, F2, F3, and F4 are ≤ 7.0 kPa, 7.1–9.4 kPa, 9.5–12.4 kPa, and ≥ 12.5 kPa, respectively. Indetermined results indicate primary LSM failure or unreliable LSM. Concordance of SVR 4 and SVR 12 Among 1002 patients who achieved SVR 4 , 987 (98.5%) achieved SVR 12 . Characteristics of the remaining 15 patients who initially achieved SVR 4 but experienced viral relapse at off-treatment week 12 were detailed in Supplementary Table 1. Conversely, all 9 patients who had detectable HCV RNA levels at off-treatment week 4 remained viremic at off-treatment week 12. As a result, the sensitivity of testing HCV RNA levels at off-treatment week 4 was 100% (95% CI: 99.6%-100%), with a specificity of 37.5% (95% CI: 18.8%-59.4%), a PPV of 98.5% (95% CI: 98.0%-98.9%), a NPV of 100% (95% CI: 66.4%-100%), a LR + of 1.60 (95% CI: 1.17%-2.18%), and a LR- of 0. Among the 526 patients treated with pangenotypic DAAs, one out of the 521 patients who achieved SVR 4 tested positive for HCV RNA at off-treatment week 12. This yielded a sensitivity of 100% (95% CI: 99.3%-100%), a specificity of 80.0% (95% CI: 23.8%-99.5%), a PPV of 99.8% (95% CI: 98.9%-100%), a NPV of 100% (95% CI: 39.8%-100%), a LR + of 5.00 (95% CI: 0.87–28.86), and a LR- of 0%. Among the 485 patients treated with genotype-specific DAAs, 14 out of 480 patients who achieved SVR 4 tested positive for HCV RNA at off-treatment week 12. This resulted in a sensitivity of 100% (95% CI: 99.2%-100%), a specificity of 26.3% (95% CI: 9.2%-51.2%), a PPV of 97.1% (95% CI: 96.2%-97.8%), a NPV of 100% (95% CI: 47.8%-100%), a LR + of 1.36 (95% CI: 1.04–1.78), and a LR- of 0% (Table 2 ). Table 2 Concordance of SVR 4 and SVR 12 Patient population SVR 4 (n) SVR 12 (n) SVR 4 to predict SVR 12 , (95% CI) Yes No Sensitivity, % Specificity, % PPV, % NPV, % LR+ LR- Overall (N = 1011) Yes (1002) 987 15 100 (99.6–100) 37.5 (18.8–59.4) 98.5 (98.0-98.9) 100 (66.4–100) 1.60 (1.17–2.18) 0 - No (9) 0 9 Pangenotypic DAAs (N = 526) Yes (522) 521 1 100 (99.3–100) 80.0 (23.8–99.5) 99.8 (98.9–100) 100 (39.8–100) 5.00 (0.87–28.86) 0 - No (4) 0 4 Genotype-specific DAAs (N = 485) Yes (480) 466 14 100 (99.2–100) 26.3 (9.2–51.2) 97.1 (96.2–97.8) 100 (47.8–100) 1.36 (1.04–1.78) 0 - No (5) 0 5 SVR, sustained virologic response; CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value; LR+, positive likelihood ratio; LR-, negative likelihood ratio; DAA, direct-acting antiviral. The PPV of achieving SVR 4 to predict SVR 12 in patients treated with pangenotypic DAAs was significantly higher than in those receiving genotype-specific DAAs (99.8% [95% CI: 98.9%-100%] versus 97.1% [95% CI: 96.2%-97.8%], p < 0.001). Concordance of SVR 12 and SVR 24 Among the 925 patients who SVR 12 , all of them achieved SVR 24 , irrespective of the type of DAA treatment. Additionally, all 18 patients confirmed to have experienced viral relapse at off-treatment week 12 were tested positive for serum HCV RNA at off-treatment week 24 (Table 3 ). No additional cases of relapse were detected between off-treatment weeks 12 and 24. Table 3 Concordance of SVR 12 and SVR 24 Patient population SVR 4 (n) SVR 12 (n) SVR 4 to predict SVR 12 , (95% CI) Yes No Sensitivity, % Specificity, % PPV, % NPV, % LR+ LR- Overall (N = 943) Yes (925) 925 0 100 (99.6–100) 100 (81.5–100) 100 (99.6–100) 100 (81.5–100) - 0 - No (18) 0 18 Pangenotypic DAAs (N = 476) Yes (473) 473 0 100 (99.2–100) 100 (29.2–100) 100 (99.2–100) 100 (29.2–100) - 0 - No (3) 0 3 Genotype-specific DAAs (N = 467) Yes (452) 452 0 100 (99.2–100) 100 (78.2–100) 100 (99.2–100) 100 (78.2–100) - 0 - No (15) 0 15 SVR, sustained virologic response; CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value; LR+, positive likelihood ratio; LR-, negative likelihood ratio; DAA, direct-acting antiviral. Table 4 Univariate and multivariate logistic regression analysis of factors associated with off-therapy week 12 outcomes in patients with SVR 4 Parameter Univariate analysis Multivariate analysis Concordant (N = 987) Discordant (N = 15) Crude OR (95% CI) * p value Adjusted OR (95% CI) p value DAA regimen Pangenotypic 521 1 15.65 (2.05-119.49) 0.008 11.13 (1.43–86.48) 0.021 Genotype-specific 466 14 Ref Ref Age ≤ 50 years 290 1 5.83 (0.76–44.50) 0.09 2.81 (0.35–22.80) 0.33 > 50 years 697 14 Ref Ref Sex Female 433 5 1.56 (0.53–4.61) 0.42 - - Male 554 10 Ref HIV coinfection Yes 163 1 2.77 (0.36–21.21) 0.33 - - No 824 14 Ref ESKD Yes 160 1 2.71 (0.35–0.74) 0.34 - - No 827 14 Ref HCC history No 922 12 3.55 (0.98–12.89) 0.054 1.67 (0.42–6.62) 0.47 Yes 65 3 Ref Ref Solid organ transplantation No 929 13 2.46 (0.54–11.18) 0.31 - - Yes 58 2 Ref Fibrosis stage † 2,000,000 IU/mL 456 10 Ref HCV genotype 1 ‡ No 403 4 1.99 (0.60-6.00) 0.28 - - Yes 584 11 Ref FIB-4 score ≤ 3.25 686 6 3.42 (1.21–9.69) 0.021 1.14 (0.29–4.47) 0.85 > 3.25 301 9 Ref Ref SVR, sustained virologic response; OR, odds ratio; CI, confidence interval; DAA, direct-acting antiviral; HIV, human immunodeficiency virus; ESKD, end-stage kidney disease; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; RNA, ribonucleic acid; IU, international unit; FIB-4, fibrosis index based on four parameters. * Factors with a p value of < 0.10 in univariate analysis entered multivariate analysis. † Sixteen patients with indetermined LSM were not included in the analysis. ‡ Patients with non-HCV genotype 1 infections include those with HCV genotype 2, 3, 4 and 6 mono-infection, mixed genotype infection, and invalid genotyping. Factors associated with concordance or discordance off-treatment week 12 virologic response in patients achieving SVR 4 The univariate logistic regression analysis indicated that patients receiving pangenotypic DAAs (crude OR: 15.65 [95% CI: 2.05-119.49], p = 0.008), with a fibrosis stage of < F4 (crude OR: 4.14 [95% CI: 1.49–11.55], p = 0.007), and with a FIB-4 score of < 3.25 (crude OR: 3.42 [95% CI: 1.21–9.69], p = 0.021) significantly predicted SVR 4 and SVR 12 concordance. Age ≤ 50 years (crude OR: 5.83 [95% CI: 0.76–44.50], p = 0.09) and a history of HCC (crude OR: 3.55 [95% CI: 0.98–12.89], p = 0.0054) showed borderline significance in predicting SVR 4 and SVR 12 concordance. In the multivariate logistic regression analysis, patients treated with pangenotypic DAAs remained independently associated with concordant SVR 4 and SVR 12 (adjusted OR: 11.13 [95% CI: 1.43–86.48], p = 0.021). Discussion The development of IFN-free DAAs capable of curing over 95% of HCV patients across diverse populations has spurred the global viral elimination. The approval of pangenotypic DAAs, such as SOF/VEL, SOF/VEL/VOX, and GLE/PIB, has notably simplified the management of HCV and has diminished the necessity for intensive on-treatment monitoring. 20,21 As a result, professional guidelines now endorse the use of pangenotypic DAAs as the preferred first-line treatment for HCV due to their significant advantages. 8,22 Up to now, the standard duration for off-treatment follow-up to assess treatment outcomes has been established at 12 weeks instead of 24 weeks. This is based on numerous studies utilizing both IFN-based and IFN-free DAA regimens, which have consistently shown PPVs of SVR 12 for SVR 24 within the range of 98.0–100%. 11–15 However, in patients treated with IFN-based antiviral regimens, the agreement rates between SVR 4 and SVR 24 ranged from 91.1–96%, indicating suboptimal earlier determination of treatment outcomes. 11–13 Despite an increase in the concordance rates between SVR 4 and SVR 12 to 97.7–98.0% in patients receiving genotype-specific DAAs, approximately 2.0–2.3% of viral relapsers may be misclassified as having achieved SVR 12 . 14 A recent report evaluating the ASTRAL trials, which employed SOF/VEL for HCV treatment, indicated a notably high concordance rate of 99.7% between SVR 4 and SVR 12 . However, this study's details were limited to an abstract presentation without comprehensive information on the study design and patient characteristics. 15 Furthermore, a direct comparison regarding the performance of SVR 4 in predicting SVR 12 among patients receiving pangenotypic and genotype-specific DAAs for HCV is lacking. Consequently, there's a crucial need for further research to clarify the role of serum HCV RNA levels at off-treatment week 4 for earlier determination of treatment outcomes in the era of pangenotypic DAAs. This is particularly pertinent for specific clinical settings, including people who inject drugs (PWIDs), people living with HIV, patients with cirrhosis, and younger patients, who bear a higher risk of nonadherence to off-treatment follow-ups. 23 Our study highlighted an increase in the number of patients lost to follow-up between off-treatment weeks 4 and 24, underscoring the crucial need for an accurate predictor to early ascertain and confirm virologic outcomes following antiviral treatment. Building on the exceptional 99.7% concordance rate between SVR 4 and SVR 12 observed in the ASTRAL trials, our findings demonstrated a PPV of SVR 4 for SVR 12 among patients receiving various pangenotypic DAAs at 99.8%. This suggests that the remarkable concordance rate was consistent across different pangenotypic DAA regimens and unaffected by their specificities. 15 Within the cohort receiving pangenotypic DAAs, the agreement rates between SVR 4 and SVR 12 (99.8% versus 97.1%) and the LR+ (5.00 versus 1.36) were significantly higher compared to those in patients treated with genotype-specific DAAs. Our logistic regression analysis reaffirmed that among patients achieving SVR 4 , those treated with pangenotypic DAAs had a notably higher likelihood of attaining SVR 12 than those treated with genotype-specific DAAs. This superior efficacy of pangenotypic DAAs compared to genotype-specific DAAs or IFN-based antiviral therapies might potentially contribute to the distinctive diagnostic accuracy of SVR 4 in predicting SVR 12 , although the underlying mechanisms driving this disparity remain to be elucidated. 24–26 These findings underscore the potency of pangenotypic DAAs in ensuring more reliable early predictions of treatment outcomes compared to genotype-specific regimens, signaling a significant advancement in HCV management. Among patients who did not achieve SVR 4 , none were able to attain SVR 12 . Our findings align with earlier reports indicating that evaluating the retreatment strategy at off-treatment week 4 is viable, as viral relapse can be accurately predicted at this juncture, irrespective of the specific type of antiviral treatment administered. These results reinforce the notion that assessing the need for retreatment can be reliably determined as early as off-treatment week 4. 11–15 Finally, we examined the concordance between SVR 12 and SVR 24 in 943 patients with available data. As expected, our findings demonstrated that the HCV RNA level at off-treatment week 12 impeccably predicted the virologic response at off-treatment week 24. This confirms that waiting for treatment response until 24 weeks is unnecessary, as the data strongly support the reliability of the off-treatment week 12 assessment in predicting the virologic outcome at week 24. 11–15 This study holds significant strength in highlighting the heightened concordance between SVR 4 and SVR 12 among patients receiving pangenotypic DAAs. These findings offer substantial value in determining treatment response, aiding academic and public health reporting, and formulating early retreatment strategies for viral relapsers, which is particularly important for individuals with advanced liver disease, complex comorbidities, or those at risk of HCV transmission. While these strengths are notable, it's important to note some limitations in our study. Our analysis exclusively included patients who received DAA treatment for 8 to 24 weeks. Consequently, the findings may not be extrapolated to patients receiving DAAs for less than 8 weeks, including those who discontinued treatment prematurely or received off-label treatment. Additionally, although all viral relapsers displayed the same HCV genotype/subtype at pre-treatment and off-treatment week 12 based on the commercial HCV genotyping, the potential for HCV reinfection cannot be entirely ruled out. This is because direct sequencing and phylogenetic analysis to confirm HCV reinfection were not conducted in our study. Of particular note, according to the EASL guideline, such confirmatory analyses are typically suggested for patients exhibiting recurrent viremia beyond 12 weeks posttreatment cessation. 8 Further validation of our findings by independent groups would be beneficial to substantiate and reinforce the conclusions drawn from this study. In summary, we concluded that a four-week off-treatment follow-up period suffices to determine treatment response at off-treatment week 12 among HCV patients treated with pangenotypic DAAs. However, week 4 HCV RNA testing may not replace week 12 testing with week 4 HCV RNA testing in patients receiving genotype-specific DAAs because approximately 3% of them with SVR 4 experienced viral relapse at week 12. These results offer crucial insights into the posttreatment virological assessment, aiding healthcare providers to confirm treatment outcomes at the earliest opportunity and emphasizing the importance of timely assessment for optimal patient care. Abbreviations HCV hepatitis C virus DAA direct-acting antiviral FDC fixed-dose combination SOF/VEL sofosbuvir/velpatasvir GEL/PIB glecaprevir/pibrentasvir SOF/VEL/VOX sofosbuvir/velpatasvir/voxilaprevir WHO World Health Organization IFN interferon SVR sustained virologic response PEG-IFN peginterferon RBV ribavirin ALB-IFN albinterferon TVR telaprevir BOC boceprevir RNA ribonucleic acid LLOQ lower limit of quantification HBV hepatitis B virus HBsAg hepatitis B surface antigen HIV human immunodeficiency virus ESKD end-stage kidney disease HCC hepatocellular carcinoma LSM liver stiffness measurement VCTE vibration-controlled transient elastography FIB-4 fibrosis index based on four parameters SOF/LDV sofosbuvir/ledipasvir PrOD paritaprevir/ritonavir/ombitasvir plus dasabuvir DCV daclatasvir EBR/GZR elbasvir/grazoprevir kPa kilo Pascal PPV positive predictive value NPV negative predictive value LR likelihood ratio CI confidence interval OR odds ration PWID people who inject drugs. Declarations Ethical approval The study was approved by the Research Ethics Committee of each participating center (ID: 202401091RINA) and was conducted in accordance with the principles of Declaration of Helsinki in 1975. Financial Nil Data availability The data that support the findings of this study are available from the corresponding author, upon reasonable request. Animal research This was not an animal research. Consent to participate Each participant consented this work and provided informed consent. Consent to publish All the authors consented the publish the work. Clinical trials registration The study was not a drug trial. There was no need for clinical trial registration. Author contributions Conceptualization: Chen-Hua Liu, Jia-Horng Kao. Data curation: Chen-Hua Liu. Formal analysis: Chen-Hua Liu, Yu-Ping Chang, Jia-Horng Kao. Investigation: Chen-Hua Liu, Yu-Ping Chang, Ji-Yuh Lee, Chi-Yi Chen, Wei-Yu Kao, Chih-Lin Lin, Sheng-Shun Yang, Yu-Lueng Shih, Cheng-Yuan Peng, Fu-Jen Lee, Ming-Chang Tsai, Shang-Chin Huang, Tung-Hung Su, Tai-Chung Tseng, Chun-Jen Liu, Pei-Jer Chen, Jia-Horng Kao. Methodology: Chen-Hua Liu, Yu-Ping Chang. Project administration: Chen-Hua Liu, Yu-Ping Chang, Jia-Horng Kao. Resources: Chen-Hua Liu, Yu-Ping Chang, Ji-Yuh Lee, Chi-Yi Chen, Wei-Yu Kao, Chih-Lin Lin, Sheng-Shun Yang, Yu-Lueng Shih, Cheng-Yuan Peng, Fu-Jen Lee, Ming-Chang Tsai, Shang-Chin Huang, Tung-Hung Su, Tai-Chung Tseng, Chun-Jen Liu, Pei-Jer Chen, Jia-Horng Kao. Software: Chen-Hua Liu. Supervision: Jia-Horng Kao. Validation: Chen-Hua Liu, Yu-Ping Chang. Visualization: Chen-Hua Liu, Yu-Ping Chang. Writing – original draft: Chen-Hua Liu, Yu-Ping Chang, Jia-Horng Kao. Writing – review & editing: Chen-Hua Liu, Yu-Ping Chang, Ji-Yuh Lee, Chi-Yi Chen, Wei-Yu Kao, Chih-Lin Lin, Sheng-Shun Yang, Yu-Lueng Shih, Cheng-Yuan Peng, Fu-Jen Lee, Ming-Chang Tsai, Shang-Chin Huang, Tung-Hung Su, Tai-Chung Tseng, Chun-Jen Liu, Pei-Jer Chen, Jia-Horng Kao. Conflicts of interest All authors declare no competing interests. Acknowledgements The authors thank Hui-Ju Lin and Pin-Chin Huang for clinical data management; the 7 th Core Lab of the National Taiwan University Hospital, and the 1 st Common Laboratory of the National Taiwan University Hospital, Yun-Lin Branch, for the instrumental and technical support. References Martinello M, Solomon SS, Terrault NA, Dore GJ, Hepatitis C. Lancet. 2023;402:1085–96. Feld JJ, Jacobson IM, Hézode C, Asselah T, Ruane PJ, Gruener N, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med. 2015;373:2599–607. Liu CH, Chen PY, Chen JJ, Lo CC, Su WW, Tseng KC, et al. Sofosbuvir/velpatasvir for patients with chronic hepatitis C virus infection and compensated liver disease: real-world data in Taiwan. Hepatol Int. 2021;15:338–49. Bourlière M, Gordon SC, Flamm SL, Cooper CL, Ramji A, Tong M, et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection. N Engl J Med. 2017;376:2134–46. Liu CH, Peng CY, Liu CJ, Chen CY, Lo CC, Tseng KC, et al. Sofosbuvir/velpatasvir/voxilaprevir for patients with chronic hepatitis C virus infection previously treated with NS5A direct-acting antivirals: a real-world multicenter cohort in Taiwan. Hepatol Int. 2023;17:291–302. Zeuzem S, Foster GR, Wang S, Asatryan A, Gane E, Feld JJ, et al. Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection. N Engl J Med. 2018;378:354–69. Liu CH, Liu CJ, Hung CC, Hsieh SM, Su TH, Sun HY, et al. Glecaprevir/pibrentasvir for patients with chronic hepatitis C virus infection: real-world effectiveness and safety in Taiwan. Liver Int. 2020;40:758–68. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C: Final update of the series. J Hepatol. 2020;73:1170–218. AASLD-IDSA HCV Guidance Panel. Hepatitis C guidance 2018 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis. 2018;67:1477–92. Omata M, Kanda T, Wei L, Yu ML, Chuang WL, Ibrahim A, et al. APASL consensus statements and recommendation on treatment of hepatitis C. Hepatol Int. 2016;10:702–26. Zeuzem S, Heathcote EJ, Shiffman ML, Wright TL, Bain VG, Sherman M, et al. Twelve weeks of follow-up is sufficient for the determination of sustained virologic response in patients treated with interferon alpha for chronic hepatitis C. J Hepatol. 2003;39:106–11. Martinot-Peignoux M, Stern C, Maylin S, Ripault MP, Boyer N, Leclere L, et al. Twelve weeks posttreatment follow-up is as relevant as 24 weeks to determine the sustained virologic response in patients with hepatitis C virus receiving pegylated interferon and ribavirin. Hepatology. 2010;51:1122–6. Chen J, Florian J, Carter W, Fleischer RD, Hammerstrom TS, Jadhav PR et al. Earlier sustained virologic response end points for regulatory approval and dose selection of hepatitis C therapies. Gastroenterology. 2013;144:1450-5.e2. Yoshida EM, Sulkowski MS, Gane EJ, Herring RW Jr, Ratziu V, Ding X, et al. Concordance of sustained virological response 4, 12, and 24 weeks post-treatment with sofosbuvir-containing regimens for hepatitis C virus. Hepatology. 2015;61:41–5. Sulkowski M, Feld J, Reau NS, Ni L, Scherbakovsky S, Hernández C, et al. Concordance of SVR 4-12-24 timepoints in an era of reduced sustained virologic response (SVR) determination. J Hepatol. 2021;75:770. Liu CH, Sun HY, Peng CY, Hsieh SM, Yang SS, Kao WY, et al. Hepatitis C virus reinfection in people with HIV in Taiwan after achieving sustained virologic response with antiviral treatment: the RECUR study. Open Forum Infect Dis. 2022;9:ofac348. Liu CH, Liang CC, Liu CJ, Lin CL, Su TH, Yang HC, et al. Comparison of Abbott RealTime HCV Genotype II with Versant Line Probe Assay 2.0 for hepatitis C virus genotyping. J Clin Microbiol. 2015;53:1754–7. Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43:1317–25. Castera L, Forns X, Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol. 2008;48:835–47. Dore GJ, Feld JJ, Thompson A, Martinello M, Muir AJ, Agarwal K, et al. Simplified monitoring for hepatitis C virus treatment with glecaprevir plus pibrentasvir, a randomised non-inferiority trial. J Hepatol. 2020;72:431–40. Solomon SS, Wagner-Cardoso S, Smeaton L, Sowah LA, Wimbish C, Robbins G, et al. A minimal monitoring approach for the treatment of hepatitis C virus infection (ACTG A5360 [MINMON]): a phase 4, open-label, single-arm trial. Lancet Gastroenterol Hepatol. 2022;7:307–17. Ghany MG, Morgan TR, AASLD-IDSA Hepatitis C. Guidance Panel. Hepatitis C guidance 2019 update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America recommendations for testing, managing, and treating hepatitis C virus infection. Hepatology. 2020;71:686–721. Darvishian M, Wong S, Binka M, Yu A, Ramji A, Yoshida EM, et al. Loss to follow-up: A significant barrier in the treatment cascade with direct-acting therapies. J Viral Hepat. 2020;27:243–60. Pham LV, Jensen SB, Fahnøe U, Pedersen MS, Tang Q, Ghanem L, et al. HCV genotype 1–6 NS3 residue 80 substitutions impact protease inhibitor activity and promote viral escape. J Hepatol. 2019;70:388–97. Gottwein JM, Pham LV, Mikkelsen LS, Ghanem L, Ramirez S, Scheel TKH, et al. Efficacy of NS5A inhibitors against hepatitis C virus genotypes 1–7 and escape variants. Gastroenterology. 2018;154:1435–48. Keating GM. Sofosbuvir: a review of its use in patients with chronic hepatitis C. Drugs. 2014;74:1127–46. Supplementary Files SVR4inpangenotypicDAAsSupplementaryTableHI.docx Cite Share Download PDF Status: Published Journal Publication published 30 Apr, 2024 Read the published version in Journal of Medical Virology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3876749","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":268147818,"identity":"ab408a14-491a-4c90-bc5c-55ab2cfe295c","order_by":0,"name":"Chen-Hua Liu","email":"","orcid":"","institution":"National Taiwan University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chen-Hua","middleName":"","lastName":"Liu","suffix":""},{"id":268147819,"identity":"b32d77d7-33b7-4b16-8cfc-54bf60674871","order_by":1,"name":"Yu-Ping Chang","email":"","orcid":"","institution":"National Taiwan University 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12.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3876749/v1/e91d7f72da56ca3f5a289a77.jpg"},{"id":57053586,"identity":"44e877f7-68e7-4a11-837d-4c8516e12dca","added_by":"auto","created_at":"2024-05-24 03:55:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1639488,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3876749/v1/8f16fd72-e30d-4031-bd9b-fa924cd57e0f.pdf"},{"id":50040880,"identity":"7ae657d9-ca55-45f7-8a26-477d00d904bb","added_by":"auto","created_at":"2024-01-23 15:33:49","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":93203,"visible":true,"origin":"","legend":"","description":"","filename":"SVR4inpangenotypicDAAsSupplementaryTableHI.docx","url":"https://assets-eu.researchsquare.com/files/rs-3876749/v1/10faf7664b3bb0a81d4b6d14.docx"}],"financialInterests":"","formattedTitle":"Four weeks of off-treatment follow-up is sufficient to determine virologic responses at off-treatment week 12 in patients with hepatitis C virus infection receiving pangenotypic direct-acting antivirals","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe management of hepatitis C virus (HCV) infection has undergone a paradigm shift since the advent of direct-acting antivirals (DAAs).\u003csup\u003e1\u003c/sup\u003e With the rapid evolution of new DAA regimens, the fixed-dose combination (FDC) of pangenotypic DAAs, including sofosbuvir/velpatasvir (SOF/VEL), glecaprevir/pibrentasvir (GLE/PIB), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX), are now recommended by the professional societies as the primary treatment agents for HCV due to their ease of use, high potency, and excellent safety profiles.\u003csup\u003e2\u0026ndash;10\u003c/sup\u003e This remarkable achievement has prompted the World Health Organization (WHO) in 2015 to set a target for HCV elimination by 2030, which includes achieving 90% diagnosis, an 80% of treatment uptake, and a 65% reduction in mortality, all aiming to combat the adverse health consequences associated with HCV.\u003c/p\u003e \u003cp\u003eIn the era when interferon (IFN) was the primary treatment for HCV, the key indicator for successfully viral eradication was the sustained virologic response (SVR), often assessed at off-treatment week 24. Two pivotal studies have shown that achieving SVR at off-therapy week 12 (SVR\u003csub\u003e12\u003c/sub\u003e) following peginterferon (PEG-IFN) plus ribavirin (RBV) predicted SVR\u003csub\u003e24\u003c/sub\u003e in 98\u0026ndash;99.7%.\u003csup\u003e11,12\u003c/sup\u003e Additionally, the positive predictive value (PPV) of SVR\u003csub\u003e4\u003c/sub\u003e in forecasting SVR\u003csub\u003e24\u003c/sub\u003e was 96%.\u003csup\u003e12\u003c/sup\u003e On the other way, patients experiencing viral relapse at off-treatment week 24 typically exhibited detectable viremia earlier, between off-treatment weeks 4 to 8.\u003csup\u003e11\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSubsequent pooled analyses of various clinical trials and drug development programs involving PEG-IFN plus RBV, albinterferon (ALB-IFN) plus RBV, as well as the first-generation DAAs, telaprevir (TVR) and boceprevir (BOC), in combination with PEG-IFN plus RBV, demonstrated excellent concordance rates between SVR\u003csub\u003e12\u003c/sub\u003e and SVR\u003csub\u003e24\u003c/sub\u003e, ranging from 98.3\u0026ndash;100%..\u003csup\u003e13\u003c/sup\u003e However, the ability of SVR\u003csub\u003e4\u003c/sub\u003e to predict SVR\u003csub\u003e24\u003c/sub\u003e was found to be suboptimal for HCV genotype 1 and genotype 2/3 infections, with PPVs of 91.1% and 93.3%, respectively.\u003c/p\u003e \u003cp\u003eFollowing the widespread adoption of IFN-free DAAs post-2013, Yoshida et al. conducted an evaluation involving 863 patients with HCV genotype 1 to 6 infections treated with sofosbuvir (SOF) plus RBV with or without PEG-IFN combination.\u003csup\u003e14\u003c/sup\u003e Their study found a 100% concordance rate between SVR\u003csub\u003e12\u003c/sub\u003e and SVR\u003csub\u003e24\u003c/sub\u003e for patients with HCV genotype 1, 4, and 6 infections receiving SOF plus PEG-IFN/RBV. For those with genotype 2 and 3 infections receiving SOF plus RBV, the rates were 100% and 99.1%, respectively. Notably, the PPVs of SVR\u003csub\u003e4\u003c/sub\u003e for predicting SVR\u003csub\u003e12\u003c/sub\u003e ranged from 97.7\u0026ndash;98.0%, surpassing the PPVs of SVR\u003csub\u003e4\u003c/sub\u003e for patients receiving PEG-IFN plus RBV. Furthermore, the negative predictive values (NPVs) of SVR\u003csub\u003e4\u003c/sub\u003e to predict SVR\u003csub\u003e12\u003c/sub\u003e, and of SVR\u003csub\u003e12\u003c/sub\u003e to predict SVR\u003csub\u003e24\u003c/sub\u003e, were both 100%. In a separate study by Sulkowski et al., evaluating patients treated with the pangenotypic sofosbuvir/velpatasvir (SOF/VEL) in the ASTRAL phase III program, the PPVs of SVR\u003csub\u003e4\u003c/sub\u003e to predict SVR\u003csub\u003e12\u003c/sub\u003e and SVR\u003csub\u003e12\u003c/sub\u003e to predict SVR\u003csub\u003e24\u003c/sub\u003e were 99.7% and 100%, respectively. Additionally, both SVR\u003csub\u003e4\u003c/sub\u003e and SVR\u003csub\u003e12\u003c/sub\u003e demonstrated 100% NPVs in predicting viral relapse at off-treatment weeks 12 and 24.\u003csup\u003e15\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe reports from clinical trials indicate an increasing trend in the PPV of achieving SVR\u003csub\u003e4\u003c/sub\u003e to predict the likelihood of achieving SVR\u003csub\u003e12\u003c/sub\u003e, particularly as treatments have shifted from IFN-based therapies to DAAs. However, there's a lack of real-world data assessing the clinical relevance of SVR\u003csub\u003e4\u003c/sub\u003e in predicting SVR\u003csub\u003e12\u003c/sub\u003e among patients receiving both pangenotypic and genotype-specific DAAs. Given that the SVR\u003csub\u003e12\u003c/sub\u003e rates often exceed 95% with short courses of pangenotypic DAAs, this holds significant importance from a public health perspective, especially for patients who might be at risk of not adhering to off-treatment follow-ups. Therefore, our aim was to evaluate and compare how effectively SVR\u003csub\u003e4\u003c/sub\u003e predicted SVR\u003csub\u003e12\u003c/sub\u003e in patients treated with both pangenotypic and genotype-specific DAAs for HCV. These results may make healthcare providers assess the treatment responses earlier in daily clinical practice.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eBetween January 2015 and December 2023, individuals aged 18 or older who achieved undetectable levels of HCV ribonucleic acid (RNA) (Cobas TaqMan HCV Test v2.0, Roche Diagnostics GmbH, Mannheim, Germany, lower limit of quantification [LLOQ]: 15 IU/mL) at the end of treatment, following a regimen of 8 to 24 weeks of IFN-free DAAs for HCV infection, were retrospectively enrolled at 11 academic centers in Taiwan. Participants were confirmed to have HCV infection if they tested positive for quantifiable serum HCV RNA levels. Following the achievement of an end-of-treatment virologic response, these patients underwent serum HCV RNA testing at off-treatment weeks 4, 12, and 24. The study's treatment outcomes were categorized into SVR\u003csub\u003e12\u003c/sub\u003e, viral relapse (defined as detectable serum HCV RNA at off-treatment week 12 with the same HCV genotype/subtype or strains as pretreatment), and reinfection (defined as detectable serum HCV RNA at off-treatment week 12 with a different HCV genotype/subtype or strains compared to pretreatment).\u003csup\u003e16\u003c/sup\u003e The primary endpoint of the study analyzed the diagnostic accuracy of serum HCV RNA level at off-treatment week 4 to predict patients who achieved SVR\u003csub\u003e12\u003c/sub\u003e or experienced viral relapse at off-treatment week 12. Patients were excluded from the primary analysis if they were diagnosed with reinfection, lacked available pretreatment HCV genotyping (Roche Cobas HCV GT, Roche Diagnostics GmbH, Mannheim, Germany, or Abbott RealTi\u003cem\u003eme\u003c/em\u003e HCV Genotype II, Abbott Laboratories, Abbott Park, Illinois, USA), or did not undergo serum HCV RNA testing at off-treatment weeks 4 and 12.\u003csup\u003e17\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAmong patients who were confirmed to have achieved SVR\u003csub\u003e12\u003c/sub\u003e and those who experienced viral relapse at off-treatment week 12, the secondary endpoint was to evaluate the diagnostic accuracy of serum HCV RNA level at off-treatment week 12 in predicting patients who would attain either SVR\u003csub\u003e24\u003c/sub\u003e or viral relapse at off-treatment week 24. Patients who were reinfected with HCV at off-treatment week 24 or lacked available serum HCV RNA testing at off-treatment week 24 were excluded from the secondary analysis. The study received approval from the Research Ethics Committee of each participating center, and was conducted in accordance with ethical principles, and the guidelines outlined in the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003ePretreatment demographic information, encompassing age, sex, hepatitis B virus (HBV) coinfection, identified as the presence of HBV surface antigen (HBsAg) (Abbott Architect HBsAg qualitative assay, Abbott Laboratories, Abbott Park, Illinois, USA), human immunodeficiency virus (HIV) coinfection, identified as the presence of HIV antibody (anti-HIV) (Abbott Architect HIV Ag/Ab Combo, Abbott Laboratories), presence of decompensated cirrhosis, end-stage kidney disease (ESKD) or solid organ transplantation, a history of hepatocellular carcinoma (HCC), serum HCV RNA level and genotype/subtype, DAA regimen, treatment duration, the stage of hepatic fibrosis assessed through liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) ((FibroScan\u0026reg;, Echosens, Paris, France), and fibrosis index based on four parameters (FIB-4) were all evaluated.\u003csup\u003e17.18\u003c/sup\u003e Additionally, data were collected for serum HCV RNA levels at the end of treatment, as well as at off-treatment weeks 4, 12, and 24. For patients with detectable HCV RNA levels at off-treatment weeks 12 and 24, information regarding HCV genotyping and direct sequencing of the HCV genome with phylogenetic analysis was assessed when available to confirm relapse or reinfection.\u003c/p\u003e \u003cp\u003eThe pangenotypic DAA regimens encompassed SOF/VEL, GLE/PIB, and SOF/VEL/VOX, while the genotype-specific DAA regimens included sofosbuvir/ledipasvir (SOF/LDV), SOF plus daclatasvir (DCV), SOF plus RBV, paritaprevir/ritonavir/ombitasvir plus dasabuvir (PrOD), and elbasvir/grazoprevir (EBR/GZR). The cut-off values used for LSM to categorize fibrosis stages were as follows: \u0026le; 7.0 kilopascals (kPa) for F0-F1, 7.1\u0026ndash;9.4 kPa for F2, 9.5\u0026ndash;12.4 kPa for F3, and \u0026ge;\u0026thinsp;12.5 kPa for F4.\u003csup\u003e19\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eThe statistical analyses were conducted using IBM's SPSS Statistics Version 26.0. Pretreatment characteristics were presented as numbers (percentages) for categorical variables. A comparison between patients receiving pangenotypic and genotype-specific DAAs was performed using the chi-squared test.\u003c/p\u003e \u003cp\u003eThe sensitivity, specificity, PPV, NPV, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) with 95% confidence intervals (CI) of SVR\u003csub\u003e4\u003c/sub\u003e to predict SVR\u003csub\u003e12\u003c/sub\u003e in the entire population and among those receiving pangenotypic and genotype-specific DAAs were calculated and presented. Additionally, the same parameters were used to describe the concordance between SVR\u003csub\u003e12\u003c/sub\u003e and SVR\u003csub\u003e24\u003c/sub\u003e. Among patients who achieved SVR\u003csub\u003e4\u003c/sub\u003e, univariate logistic regression analysis was employed to assess factors associated with the concordance or discordance for SVR\u003csub\u003e12\u003c/sub\u003e. Results were presented as odds ratios (OR) with 95% CI. Subsequently, multivariate analysis was conducted to identify independent factors associated with the concordance of SVR\u003csub\u003e4\u003c/sub\u003e and SVR\u003csub\u003e12\u003c/sub\u003e for variables with a p-value less than 0.10 in the univariate analysis. All statistical analyses were two-tailed, and the statistical significance was defined as a p-value less than 0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePatient Characteristics\u003c/h2\u003e \u003cp\u003eAmong 1051 patients who achieved an end-of-treatment virologic response using IFN-free DAAs for HCV, 40 were excluded from the study due to a lack of off-treatment week 4 (n\u0026thinsp;=\u0026thinsp;11) and off-treatment week 12 (n\u0026thinsp;=\u0026thinsp;28) HCV RNA testing, and HCV reinfection (n\u0026thinsp;=\u0026thinsp;1). Subsequently, the remaining 1011 patients were included in the primary endpoint analysis. Among them, 987 achieved SVR\u003csub\u003e12\u003c/sub\u003e, while 24 experienced viral relapse. For the secondary endpoint analysis, 943 out of the 1011 patients from the primary analysis were included. This exclusion accounted for 68 patients due to a lack of off-treatment week 24 HCV RNA testing (n\u0026thinsp;=\u0026thinsp;65) and HCV reinfection (n\u0026thinsp;=\u0026thinsp;3) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Among the four cases of HCV reinfection, three demonstrated HCV genotype/subtype switches, while the remaining one patient with HCV genotype 1b infection both pretreatment and at the time of reinfection at off-treatment week 24 was confirmed to have HCV reinfection through direct sequencing and phylogenetic mapping. All individuals experiencing viral relapse exhibited the same HCV genotype/subtype between pretreatment and the time of viral relapse, as determined by commercial HCV genotyping without additional direct sequencing and phylogenetic mapping.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn the baseline characteristics, 526 patients (52.0%) received pangenotypic DAAs, while 485 (48.0%) were treated with genotype-specific DAAs. Those receiving pangenotypic DAAs showed a higher percentage of males, HBV and HIV coinfection, decompensated cirrhosis, HCV RNA levels\u0026thinsp;\u0026gt;\u0026thinsp;2,000,000 IU/mL, shorter treatment duration, SVR\u003csub\u003e12\u003c/sub\u003e rate, and F0-F1 hepatic fibrosis compared to those receiving genotype-specific DAAs. Conversely, patients treated with genotype-specific DAAs had a higher percentage of individuals over the age of 50, ESKD, a history of HCC, HCV genotype 1 infection, and a FIB-4 score\u0026thinsp;\u0026gt;\u0026thinsp;3.25 (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall (N\u0026thinsp;=\u0026thinsp;1011)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePangenotypic DAAs (n\u0026thinsp;=\u0026thinsp;526)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGenotype-specific DAAs (n\u0026thinsp;=\u0026thinsp;485)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u0026thinsp;\u0026gt;\u0026thinsp;50 years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e716 (70.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e324 (61.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e392 (80.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e570 (56.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e322 (61.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e248 (51.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHBV coinfection\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65 (6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHIV coinfection\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e165 (16.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e134 (25.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDecompensated cirrhosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e48 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eESKD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e161 (15.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e107 (22.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSolid organ transplantation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e61 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHCC history\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e69 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47 (9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHCV RNA\u0026thinsp;\u0026gt;\u0026thinsp;2,000,000 IU/mL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e469 (46.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e269 (51.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e200 (41.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHCV genotype\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 \u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e45 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e548 (54.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e170 (32.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e378 (77.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e321 (31.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e241 (45.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80 (16.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e60 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers \u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17 (1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDAA regimen\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGLE/PIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e133 (13.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e133 (25.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOF/VEL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e378 (37.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e378 (71.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOF/VEL/VOX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e191 (18.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e191 (39.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEBR/GZR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e62 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62 (12.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOF plus RBV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOF/LDV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e167 (16.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e167 (34.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOF plus DCV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e44 (4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTreatment duration, week\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e115 (11.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110 (20.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e862 (85.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e389 (74.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e473 (97.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTreatment outcome\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSVR\u003csub\u003e12\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e987 (97.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e521 (99.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e466 (96.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRelapse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFibrosis stage (METAVIR)\u003c/b\u003e \u003csup\u003e\u003cb\u003e\u0026sect;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF0-F1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e541 (53.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e348 (66.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e193 (39.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e139 (14.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 (11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e92 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56 (11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e222 (22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71 (13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e151 (31.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndetermined\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17 (1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFIB-4 score\u0026thinsp;\u0026gt;\u0026thinsp;3.25, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e315 (31.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110 (20.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e205 (42.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eDAA, direct-acting antiviral; HBV, hepatitis B virus; HIV, human immunodeficiency virus; ESKD, end-stage kidney disease; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; RNA, ribonucleic acid; IU, international unit; GLE/PIB, glecaprevir/pibrentasvir; SOF/VEL, sofosbuvir/velpatasvir; SOF/VEL/VOX, sofosbuvir/velpatasvir/voxilaprevir; PrOD, paritaprevir/ritonavir/ombitasvir plus dasabuvir; EBR/GZR, elbasvir/grazoprevir; RBV, ribavirin; SOF/LDV, sofosbuvir/ledipasvir; DCV, daclatasvir; SVR\u003csub\u003e12\u003c/sub\u003e, sustained virologic response at off-treatment week 12; FIB-4, fibrosis index based on four parameters.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cb\u003e*\u003c/b\u003e Pangenotypic DAA group versus genotype-specific DAA group, using chi-square tests.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u0026dagger; Unsubtypable genotype 1 infection.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u0026Dagger; Including mixed genotype infection, and invalid genotyping.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u0026sect; Assessing liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE). The cut-off values of LSM for a hepatic fibrosis stage of F0-1, F2, F3, and F4 are \u0026le;\u0026thinsp;7.0 kPa, 7.1\u0026ndash;9.4 kPa, 9.5\u0026ndash;12.4 kPa, and \u0026ge;\u0026thinsp;12.5 kPa, respectively. Indetermined results indicate primary LSM failure or unreliable LSM.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eConcordance of SVR\u003csub\u003e4\u003c/sub\u003e and SVR\u003csub\u003e12\u003c/sub\u003e\u003c/h2\u003e \u003cp\u003eAmong 1002 patients who achieved SVR\u003csub\u003e4\u003c/sub\u003e, 987 (98.5%) achieved SVR\u003csub\u003e12\u003c/sub\u003e. Characteristics of the remaining 15 patients who initially achieved SVR\u003csub\u003e4\u003c/sub\u003e but experienced viral relapse at off-treatment week 12 were detailed in Supplementary Table\u0026nbsp;1. Conversely, all 9 patients who had detectable HCV RNA levels at off-treatment week 4 remained viremic at off-treatment week 12. As a result, the sensitivity of testing HCV RNA levels at off-treatment week 4 was 100% (95% CI: 99.6%-100%), with a specificity of 37.5% (95% CI: 18.8%-59.4%), a PPV of 98.5% (95% CI: 98.0%-98.9%), a NPV of 100% (95% CI: 66.4%-100%), a LR\u0026thinsp;+\u0026thinsp;of 1.60 (95% CI: 1.17%-2.18%), and a LR- of 0.\u003c/p\u003e \u003cp\u003eAmong the 526 patients treated with pangenotypic DAAs, one out of the 521 patients who achieved SVR\u003csub\u003e4\u003c/sub\u003e tested positive for HCV RNA at off-treatment week 12. This yielded a sensitivity of 100% (95% CI: 99.3%-100%), a specificity of 80.0% (95% CI: 23.8%-99.5%), a PPV of 99.8% (95% CI: 98.9%-100%), a NPV of 100% (95% CI: 39.8%-100%), a LR\u0026thinsp;+\u0026thinsp;of 5.00 (95% CI: 0.87\u0026ndash;28.86), and a LR- of 0%. Among the 485 patients treated with genotype-specific DAAs, 14 out of 480 patients who achieved SVR\u003csub\u003e4\u003c/sub\u003e tested positive for HCV RNA at off-treatment week 12. This resulted in a sensitivity of 100% (95% CI: 99.2%-100%), a specificity of 26.3% (95% CI: 9.2%-51.2%), a PPV of 97.1% (95% CI: 96.2%-97.8%), a NPV of 100% (95% CI: 47.8%-100%), a LR\u0026thinsp;+\u0026thinsp;of 1.36 (95% CI: 1.04\u0026ndash;1.78), and a LR- of 0% (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eConcordance of SVR\u003csub\u003e4\u003c/sub\u003e and SVR\u003csub\u003e12\u003c/sub\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePatient population\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSVR\u003csub\u003e4\u003c/sub\u003e (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eSVR\u003csub\u003e12\u003c/sub\u003e (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c10\" namest=\"c5\"\u003e \u003cp\u003eSVR\u003csub\u003e4\u003c/sub\u003e to predict SVR\u003csub\u003e12\u003c/sub\u003e, (95% CI)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSensitivity, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSpecificity, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePPV, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNPV, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLR+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eLR-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eOverall\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(N\u0026thinsp;=\u0026thinsp;1011)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes (1002)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e987\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(99.6\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e37.5\u003c/p\u003e \u003cp\u003e(18.8\u0026ndash;59.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e98.5\u003c/p\u003e \u003cp\u003e(98.0-98.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(66.4\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1.60\u003c/p\u003e \u003cp\u003e(1.17\u0026ndash;2.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo (9)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003ePangenotypic DAAs\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(N\u0026thinsp;=\u0026thinsp;526)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes (522)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e521\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(99.3\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e80.0\u003c/p\u003e \u003cp\u003e(23.8\u0026ndash;99.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e99.8\u003c/p\u003e \u003cp\u003e(98.9\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(39.8\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e5.00\u003c/p\u003e \u003cp\u003e(0.87\u0026ndash;28.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo (4)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eGenotype-specific DAAs\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(N\u0026thinsp;=\u0026thinsp;485)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes (480)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e466\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(99.2\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e26.3\u003c/p\u003e \u003cp\u003e(9.2\u0026ndash;51.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e97.1\u003c/p\u003e \u003cp\u003e(96.2\u0026ndash;97.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(47.8\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1.36\u003c/p\u003e \u003cp\u003e(1.04\u0026ndash;1.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo (5)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eSVR, sustained virologic response; CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value; LR+, positive likelihood ratio; LR-, negative likelihood ratio; DAA, direct-acting antiviral.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe PPV of achieving SVR\u003csub\u003e4\u003c/sub\u003e to predict SVR\u003csub\u003e12\u003c/sub\u003e in patients treated with pangenotypic DAAs was significantly higher than in those receiving genotype-specific DAAs (99.8% [95% CI: 98.9%-100%] versus 97.1% [95% CI: 96.2%-97.8%], p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eConcordance of SVR\u003csub\u003e12\u003c/sub\u003e and SVR\u003csub\u003e24\u003c/sub\u003e\u003c/h2\u003e \u003cp\u003eAmong the 925 patients who SVR\u003csub\u003e12\u003c/sub\u003e, all of them achieved SVR\u003csub\u003e24\u003c/sub\u003e, irrespective of the type of DAA treatment. Additionally, all 18 patients confirmed to have experienced viral relapse at off-treatment week 12 were tested positive for serum HCV RNA at off-treatment week 24 (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). No additional cases of relapse were detected between off-treatment weeks 12 and 24.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eConcordance of SVR\u003csub\u003e12\u003c/sub\u003e and SVR\u003csub\u003e24\u003c/sub\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePatient population\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSVR\u003csub\u003e4\u003c/sub\u003e (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eSVR\u003csub\u003e12\u003c/sub\u003e (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c10\" namest=\"c5\"\u003e \u003cp\u003eSVR\u003csub\u003e4\u003c/sub\u003e to predict SVR\u003csub\u003e12\u003c/sub\u003e, (95% CI)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSensitivity, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSpecificity, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePPV, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNPV, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLR+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eLR-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eOverall\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(N\u0026thinsp;=\u0026thinsp;943)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes (925)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e925\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(99.6\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(81.5\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(99.6\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(81.5\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo (18)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003ePangenotypic DAAs\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(N\u0026thinsp;=\u0026thinsp;476)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes (473)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e473\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(99.2\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(29.2\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(99.2\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(29.2\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo (3)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eGenotype-specific DAAs\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(N\u0026thinsp;=\u0026thinsp;467)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes (452)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e452\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(99.2\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(78.2\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(99.2\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003cp\u003e(78.2\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo (15)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eSVR, sustained virologic response; CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value; LR+, positive likelihood ratio; LR-, negative likelihood ratio; DAA, direct-acting antiviral.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and multivariate logistic regression analysis of factors associated with off-therapy week 12 outcomes in patients with SVR\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConcordant\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;987)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDiscordant\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCrude OR (95% CI) \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAdjusted OR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDAA regimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePangenotypic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e521\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.65 (2.05-119.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.13 (1.43\u0026ndash;86.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGenotype-specific\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e466\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;50 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e290\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.83 (0.76\u0026ndash;44.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.81 (0.35\u0026ndash;22.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e697\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e433\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.56 (0.53\u0026ndash;4.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e554\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHIV coinfection\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e163\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.77 (0.36\u0026ndash;21.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e824\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eESKD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.71 (0.35\u0026ndash;0.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e827\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHCC history\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e922\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.55 (0.98\u0026ndash;12.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.67 (0.42\u0026ndash;6.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSolid organ transplantation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e929\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.46 (0.54\u0026ndash;11.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFibrosis stage\u003c/b\u003e \u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt; F4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e761\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.14 (1.49\u0026ndash;11.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.09 (0.55\u0026ndash;7.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e= F4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e210\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHCV RNA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;2,000,000 IU/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e531\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.33 (0.79\u0026ndash;6.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;2,000,000 IU/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e456\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHCV genotype 1\u003c/b\u003e \u003csup\u003e\u003cb\u003e\u0026Dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e403\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.99 (0.60-6.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e584\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFIB-4 score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;3.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e686\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.42 (1.21\u0026ndash;9.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.14 (0.29\u0026ndash;4.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;3.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e301\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eSVR, sustained virologic response; OR, odds ratio; CI, confidence interval; DAA, direct-acting antiviral; HIV, human immunodeficiency virus; ESKD, end-stage kidney disease; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; RNA, ribonucleic acid; IU, international unit; FIB-4, fibrosis index based on four parameters.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e* Factors with a p value of \u0026lt;\u0026thinsp;0.10 in univariate analysis entered multivariate analysis.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u0026dagger; Sixteen patients with indetermined LSM were not included in the analysis.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u0026Dagger; Patients with non-HCV genotype 1 infections include those with HCV genotype 2, 3, 4 and 6 mono-infection, mixed genotype infection, and invalid genotyping.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eFactors associated with concordance or discordance off-treatment week 12 virologic response in patients achieving SVR\u003csub\u003e4\u003c/sub\u003e\u003c/h2\u003e \u003cp\u003eThe univariate logistic regression analysis indicated that patients receiving pangenotypic DAAs (crude OR: 15.65 [95% CI: 2.05-119.49], p\u0026thinsp;=\u0026thinsp;0.008), with a fibrosis stage of \u0026lt;\u0026thinsp;F4 (crude OR: 4.14 [95% CI: 1.49\u0026ndash;11.55], p\u0026thinsp;=\u0026thinsp;0.007), and with a FIB-4 score of \u0026lt;\u0026thinsp;3.25 (crude OR: 3.42 [95% CI: 1.21\u0026ndash;9.69], p\u0026thinsp;=\u0026thinsp;0.021) significantly predicted SVR\u003csub\u003e4\u003c/sub\u003e and SVR\u003csub\u003e12\u003c/sub\u003e concordance. Age\u0026thinsp;\u0026le;\u0026thinsp;50 years (crude OR: 5.83 [95% CI: 0.76\u0026ndash;44.50], p\u0026thinsp;=\u0026thinsp;0.09) and a history of HCC (crude OR: 3.55 [95% CI: 0.98\u0026ndash;12.89], p\u0026thinsp;=\u0026thinsp;0.0054) showed borderline significance in predicting SVR\u003csub\u003e4\u003c/sub\u003e and SVR\u003csub\u003e12\u003c/sub\u003e concordance. In the multivariate logistic regression analysis, patients treated with pangenotypic DAAs remained independently associated with concordant SVR\u003csub\u003e4\u003c/sub\u003e and SVR\u003csub\u003e12\u003c/sub\u003e (adjusted OR: 11.13 [95% CI: 1.43\u0026ndash;86.48], p\u0026thinsp;=\u0026thinsp;0.021).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe development of IFN-free DAAs capable of curing over 95% of HCV patients across diverse populations has spurred the global viral elimination. The approval of pangenotypic DAAs, such as SOF/VEL, SOF/VEL/VOX, and GLE/PIB, has notably simplified the management of HCV and has diminished the necessity for intensive on-treatment monitoring. \u003csup\u003e20,21\u003c/sup\u003e As a result, professional guidelines now endorse the use of pangenotypic DAAs as the preferred first-line treatment for HCV due to their significant advantages.\u003csup\u003e8,22\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eUp to now, the standard duration for off-treatment follow-up to assess treatment outcomes has been established at 12 weeks instead of 24 weeks. This is based on numerous studies utilizing both IFN-based and IFN-free DAA regimens, which have consistently shown PPVs of SVR\u003csub\u003e12\u003c/sub\u003e for SVR\u003csub\u003e24\u003c/sub\u003e within the range of 98.0\u0026ndash;100%.\u003csup\u003e11\u0026ndash;15\u003c/sup\u003e However, in patients treated with IFN-based antiviral regimens, the agreement rates between SVR\u003csub\u003e4\u003c/sub\u003e and SVR\u003csub\u003e24\u003c/sub\u003e ranged from 91.1\u0026ndash;96%, indicating suboptimal earlier determination of treatment outcomes.\u003csup\u003e11\u0026ndash;13\u003c/sup\u003e Despite an increase in the concordance rates between SVR\u003csub\u003e4\u003c/sub\u003e and SVR\u003csub\u003e12\u003c/sub\u003e to 97.7\u0026ndash;98.0% in patients receiving genotype-specific DAAs, approximately 2.0\u0026ndash;2.3% of viral relapsers may be misclassified as having achieved SVR\u003csub\u003e12\u003c/sub\u003e.\u003csup\u003e14\u003c/sup\u003e A recent report evaluating the ASTRAL trials, which employed SOF/VEL for HCV treatment, indicated a notably high concordance rate of 99.7% between SVR\u003csub\u003e4\u003c/sub\u003e and SVR\u003csub\u003e12\u003c/sub\u003e. However, this study's details were limited to an abstract presentation without comprehensive information on the study design and patient characteristics.\u003csup\u003e15\u003c/sup\u003e Furthermore, a direct comparison regarding the performance of SVR\u003csub\u003e4\u003c/sub\u003e in predicting SVR\u003csub\u003e12\u003c/sub\u003e among patients receiving pangenotypic and genotype-specific DAAs for HCV is lacking. Consequently, there's a crucial need for further research to clarify the role of serum HCV RNA levels at off-treatment week 4 for earlier determination of treatment outcomes in the era of pangenotypic DAAs. This is particularly pertinent for specific clinical settings, including people who inject drugs (PWIDs), people living with HIV, patients with cirrhosis, and younger patients, who bear a higher risk of nonadherence to off-treatment follow-ups.\u003csup\u003e23\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOur study highlighted an increase in the number of patients lost to follow-up between off-treatment weeks 4 and 24, underscoring the crucial need for an accurate predictor to early ascertain and confirm virologic outcomes following antiviral treatment. Building on the exceptional 99.7% concordance rate between SVR\u003csub\u003e4\u003c/sub\u003e and SVR\u003csub\u003e12\u003c/sub\u003e observed in the ASTRAL trials, our findings demonstrated a PPV of SVR\u003csub\u003e4\u003c/sub\u003e for SVR\u003csub\u003e12\u003c/sub\u003e among patients receiving various pangenotypic DAAs at 99.8%. This suggests that the remarkable concordance rate was consistent across different pangenotypic DAA regimens and unaffected by their specificities.\u003csup\u003e15\u003c/sup\u003e Within the cohort receiving pangenotypic DAAs, the agreement rates between SVR\u003csub\u003e4\u003c/sub\u003e and SVR\u003csub\u003e12\u003c/sub\u003e (99.8% versus 97.1%) and the LR+ (5.00 versus 1.36) were significantly higher compared to those in patients treated with genotype-specific DAAs. Our logistic regression analysis reaffirmed that among patients achieving SVR\u003csub\u003e4\u003c/sub\u003e, those treated with pangenotypic DAAs had a notably higher likelihood of attaining SVR\u003csub\u003e12\u003c/sub\u003e than those treated with genotype-specific DAAs. This superior efficacy of pangenotypic DAAs compared to genotype-specific DAAs or IFN-based antiviral therapies might potentially contribute to the distinctive diagnostic accuracy of SVR\u003csub\u003e4\u003c/sub\u003e in predicting SVR\u003csub\u003e12\u003c/sub\u003e, although the underlying mechanisms driving this disparity remain to be elucidated.\u003csup\u003e24\u0026ndash;26\u003c/sup\u003e These findings underscore the potency of pangenotypic DAAs in ensuring more reliable early predictions of treatment outcomes compared to genotype-specific regimens, signaling a significant advancement in HCV management.\u003c/p\u003e \u003cp\u003eAmong patients who did not achieve SVR\u003csub\u003e4\u003c/sub\u003e, none were able to attain SVR\u003csub\u003e12\u003c/sub\u003e. Our findings align with earlier reports indicating that evaluating the retreatment strategy at off-treatment week 4 is viable, as viral relapse can be accurately predicted at this juncture, irrespective of the specific type of antiviral treatment administered. These results reinforce the notion that assessing the need for retreatment can be reliably determined as early as off-treatment week 4.\u003csup\u003e11\u0026ndash;15\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eFinally, we examined the concordance between SVR\u003csub\u003e12\u003c/sub\u003e and SVR\u003csub\u003e24\u003c/sub\u003e in 943 patients with available data. As expected, our findings demonstrated that the HCV RNA level at off-treatment week 12 impeccably predicted the virologic response at off-treatment week 24. This confirms that waiting for treatment response until 24 weeks is unnecessary, as the data strongly support the reliability of the off-treatment week 12 assessment in predicting the virologic outcome at week 24.\u003csup\u003e11\u0026ndash;15\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThis study holds significant strength in highlighting the heightened concordance between SVR\u003csub\u003e4\u003c/sub\u003e and SVR\u003csub\u003e12\u003c/sub\u003e among patients receiving pangenotypic DAAs. These findings offer substantial value in determining treatment response, aiding academic and public health reporting, and formulating early retreatment strategies for viral relapsers, which is particularly important for individuals with advanced liver disease, complex comorbidities, or those at risk of HCV transmission. While these strengths are notable, it's important to note some limitations in our study. Our analysis exclusively included patients who received DAA treatment for 8 to 24 weeks. Consequently, the findings may not be extrapolated to patients receiving DAAs for less than 8 weeks, including those who discontinued treatment prematurely or received off-label treatment. Additionally, although all viral relapsers displayed the same HCV genotype/subtype at pre-treatment and off-treatment week 12 based on the commercial HCV genotyping, the potential for HCV reinfection cannot be entirely ruled out. This is because direct sequencing and phylogenetic analysis to confirm HCV reinfection were not conducted in our study. Of particular note, according to the EASL guideline, such confirmatory analyses are typically suggested for patients exhibiting recurrent viremia beyond 12 weeks posttreatment cessation.\u003csup\u003e8\u003c/sup\u003e Further validation of our findings by independent groups would be beneficial to substantiate and reinforce the conclusions drawn from this study.\u003c/p\u003e \u003cp\u003eIn summary, we concluded that a four-week off-treatment follow-up period suffices to determine treatment response at off-treatment week 12 among HCV patients treated with pangenotypic DAAs. However, week 4 HCV RNA testing may not replace week 12 testing with week 4 HCV RNA testing in patients receiving genotype-specific DAAs because approximately 3% of them with SVR\u003csub\u003e4\u003c/sub\u003e experienced viral relapse at week 12. These results offer crucial insights into the posttreatment virological assessment, aiding healthcare providers to confirm treatment outcomes at the earliest opportunity and emphasizing the importance of timely assessment for optimal patient care.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHCV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehepatitis C virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDAA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003edirect-acting antiviral\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFDC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efixed-dose combination\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSOF/VEL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esofosbuvir/velpatasvir\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGEL/PIB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eglecaprevir/pibrentasvir\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSOF/VEL/VOX\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esofosbuvir/velpatasvir/voxilaprevir\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWHO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWorld Health Organization\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIFN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einterferon\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSVR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esustained virologic response\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePEG-IFN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epeginterferon\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRBV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eribavirin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eALB-IFN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ealbinterferon\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTVR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etelaprevir\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBOC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eboceprevir\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRNA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eribonucleic acid\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLLOQ\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003elower limit of quantification\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHBV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehepatitis B virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHBsAg\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehepatitis B surface antigen\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHIV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehuman immunodeficiency virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eESKD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eend-stage kidney disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHCC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehepatocellular carcinoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLSM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eliver stiffness measurement\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVCTE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003evibration-controlled transient elastography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFIB-4\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efibrosis index based on four parameters\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSOF/LDV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e\u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003esofosbuvir/ledipasvir\u003c/div\u003e \u003cdiv class=\"Description\"\u003e\u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePrOD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eparitaprevir/ritonavir/ombitasvir plus dasabuvir\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDCV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003edaclatasvir\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEBR/GZR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eelbasvir/grazoprevir\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ekPa\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ekilo Pascal\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePPV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epositive predictive value\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNPV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enegative predictive value\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003elikelihood ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econfidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eodds ration\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePWID\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epeople who inject drugs.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Research Ethics Committee of each participating center (ID: 202401091RINA) and was conducted in accordance with the principles of Declaration of Helsinki in 1975.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNil\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author, upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnimal research\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis was not an animal research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEach participant consented this work and provided informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the authors consented the publish the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trials registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was not a drug trial. There was no need for clinical trial registration.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: Chen-Hua Liu, Jia-Horng Kao.\u003c/p\u003e\n\u003cp\u003eData curation: Chen-Hua Liu.\u003c/p\u003e\n\u003cp\u003eFormal analysis: Chen-Hua Liu,\u0026nbsp;Yu-Ping Chang,\u0026nbsp;Jia-Horng Kao.\u003c/p\u003e\n\u003cp\u003eInvestigation:\u0026nbsp;Chen-Hua Liu, Yu-Ping Chang,\u0026nbsp;Ji-Yuh Lee, Chi-Yi Chen, Wei-Yu Kao, Chih-Lin Lin, Sheng-Shun Yang, Yu-Lueng Shih,\u0026nbsp;Cheng-Yuan Peng,\u0026nbsp;Fu-Jen Lee, Ming-Chang Tsai, Shang-Chin Huang, Tung-Hung Su, Tai-Chung Tseng, Chun-Jen Liu, Pei-Jer Chen, Jia-Horng Kao.\u003c/p\u003e\n\u003cp\u003eMethodology: Chen-Hua Liu, Yu-Ping Chang.\u003c/p\u003e\n\u003cp\u003eProject administration:\u0026nbsp;Chen-Hua Liu,\u0026nbsp;Yu-Ping Chang,\u0026nbsp;Jia-Horng Kao.\u003c/p\u003e\n\u003cp\u003eResources:\u0026nbsp;Chen-Hua Liu, Yu-Ping Chang,\u0026nbsp;Ji-Yuh Lee, Chi-Yi Chen, Wei-Yu Kao, Chih-Lin Lin, Sheng-Shun Yang, Yu-Lueng Shih,\u0026nbsp;Cheng-Yuan Peng,\u0026nbsp;Fu-Jen Lee, Ming-Chang Tsai, Shang-Chin Huang, Tung-Hung Su, Tai-Chung Tseng, Chun-Jen Liu, Pei-Jer Chen, Jia-Horng Kao.\u003c/p\u003e\n\u003cp\u003eSoftware: Chen-Hua Liu.\u003c/p\u003e\n\u003cp\u003eSupervision: Jia-Horng Kao.\u003c/p\u003e\n\u003cp\u003eValidation: Chen-Hua Liu, Yu-Ping Chang.\u003c/p\u003e\n\u003cp\u003eVisualization: Chen-Hua Liu, Yu-Ping Chang.\u003c/p\u003e\n\u003cp\u003eWriting \u0026ndash; original draft: Chen-Hua Liu,\u0026nbsp;Yu-Ping Chang,\u0026nbsp;Jia-Horng Kao.\u003c/p\u003e\n\u003cp\u003eWriting \u0026ndash; review \u0026amp; editing:\u0026nbsp;Chen-Hua Liu, Yu-Ping Chang,\u0026nbsp;Ji-Yuh Lee, Chi-Yi Chen, Wei-Yu Kao, Chih-Lin Lin, Sheng-Shun Yang, Yu-Lueng Shih,\u0026nbsp;Cheng-Yuan Peng,\u0026nbsp;Fu-Jen Lee, Ming-Chang Tsai, Shang-Chin Huang, Tung-Hung Su, Tai-Chung Tseng, Chun-Jen Liu, Pei-Jer Chen, Jia-Horng Kao.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank Hui-Ju Lin and Pin-Chin Huang for clinical data management; the 7\u003csup\u003eth\u003c/sup\u003e Core Lab of the National Taiwan University Hospital, and the 1\u003csup\u003est\u003c/sup\u003e Common Laboratory of the National Taiwan University Hospital, Yun-Lin Branch, for the instrumental and technical support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMartinello M, Solomon SS, Terrault NA, Dore GJ, Hepatitis C. Lancet. 2023;402:1085\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeld JJ, Jacobson IM, H\u0026eacute;zode C, Asselah T, Ruane PJ, Gruener N, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med. 2015;373:2599\u0026ndash;607.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu CH, Chen PY, Chen JJ, Lo CC, Su WW, Tseng KC, et al. Sofosbuvir/velpatasvir for patients with chronic hepatitis C virus infection and compensated liver disease: real-world data in Taiwan. Hepatol Int. 2021;15:338\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBourli\u0026egrave;re M, Gordon SC, Flamm SL, Cooper CL, Ramji A, Tong M, et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection. N Engl J Med. 2017;376:2134\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu CH, Peng CY, Liu CJ, Chen CY, Lo CC, Tseng KC, et al. Sofosbuvir/velpatasvir/voxilaprevir for patients with chronic hepatitis C virus infection previously treated with NS5A direct-acting antivirals: a real-world multicenter cohort in Taiwan. Hepatol Int. 2023;17:291\u0026ndash;302.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeuzem S, Foster GR, Wang S, Asatryan A, Gane E, Feld JJ, et al. Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection. N Engl J Med. 2018;378:354\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu CH, Liu CJ, Hung CC, Hsieh SM, Su TH, Sun HY, et al. Glecaprevir/pibrentasvir for patients with chronic hepatitis C virus infection: real-world effectiveness and safety in Taiwan. Liver Int. 2020;40:758\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEuropean Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C: Final update of the series. J Hepatol. 2020;73:1170\u0026ndash;218.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAASLD-IDSA HCV Guidance Panel. Hepatitis C guidance 2018 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis. 2018;67:1477\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOmata M, Kanda T, Wei L, Yu ML, Chuang WL, Ibrahim A, et al. APASL consensus statements and recommendation on treatment of hepatitis C. Hepatol Int. 2016;10:702\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeuzem S, Heathcote EJ, Shiffman ML, Wright TL, Bain VG, Sherman M, et al. Twelve weeks of follow-up is sufficient for the determination of sustained virologic response in patients treated with interferon alpha for chronic hepatitis C. J Hepatol. 2003;39:106\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartinot-Peignoux M, Stern C, Maylin S, Ripault MP, Boyer N, Leclere L, et al. Twelve weeks posttreatment follow-up is as relevant as 24 weeks to determine the sustained virologic response in patients with hepatitis C virus receiving pegylated interferon and ribavirin. Hepatology. 2010;51:1122\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen J, Florian J, Carter W, Fleischer RD, Hammerstrom TS, Jadhav PR et al. Earlier sustained virologic response end points for regulatory approval and dose selection of hepatitis C therapies. Gastroenterology. 2013;144:1450-5.e2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoshida EM, Sulkowski MS, Gane EJ, Herring RW Jr, Ratziu V, Ding X, et al. Concordance of sustained virological response 4, 12, and 24 weeks post-treatment with sofosbuvir-containing regimens for hepatitis C virus. Hepatology. 2015;61:41\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSulkowski M, Feld J, Reau NS, Ni L, Scherbakovsky S, Hern\u0026aacute;ndez C, et al. Concordance of SVR 4-12-24 timepoints in an era of reduced sustained virologic response (SVR) determination. J Hepatol. 2021;75:770.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu CH, Sun HY, Peng CY, Hsieh SM, Yang SS, Kao WY, et al. Hepatitis C virus reinfection in people with HIV in Taiwan after achieving sustained virologic response with antiviral treatment: the RECUR study. Open Forum Infect Dis. 2022;9:ofac348.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu CH, Liang CC, Liu CJ, Lin CL, Su TH, Yang HC, et al. Comparison of Abbott RealTime HCV Genotype II with Versant Line Probe Assay 2.0 for hepatitis C virus genotyping. J Clin Microbiol. 2015;53:1754\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43:1317\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCastera L, Forns X, Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol. 2008;48:835\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDore GJ, Feld JJ, Thompson A, Martinello M, Muir AJ, Agarwal K, et al. Simplified monitoring for hepatitis C virus treatment with glecaprevir plus pibrentasvir, a randomised non-inferiority trial. J Hepatol. 2020;72:431\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSolomon SS, Wagner-Cardoso S, Smeaton L, Sowah LA, Wimbish C, Robbins G, et al. A minimal monitoring approach for the treatment of hepatitis C virus infection (ACTG A5360 [MINMON]): a phase 4, open-label, single-arm trial. Lancet Gastroenterol Hepatol. 2022;7:307\u0026ndash;17.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhany MG, Morgan TR, AASLD-IDSA Hepatitis C. Guidance Panel. Hepatitis C guidance 2019 update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America recommendations for testing, managing, and treating hepatitis C virus infection. Hepatology. 2020;71:686\u0026ndash;721.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDarvishian M, Wong S, Binka M, Yu A, Ramji A, Yoshida EM, et al. Loss to follow-up: A significant barrier in the treatment cascade with direct-acting therapies. J Viral Hepat. 2020;27:243\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePham LV, Jensen SB, Fahn\u0026oslash;e U, Pedersen MS, Tang Q, Ghanem L, et al. HCV genotype 1\u0026ndash;6 NS3 residue 80 substitutions impact protease inhibitor activity and promote viral escape. J Hepatol. 2019;70:388\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGottwein JM, Pham LV, Mikkelsen LS, Ghanem L, Ramirez S, Scheel TKH, et al. Efficacy of NS5A inhibitors against hepatitis C virus genotypes 1\u0026ndash;7 and escape variants. Gastroenterology. 2018;154:1435\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeating GM. Sofosbuvir: a review of its use in patients with chronic hepatitis C. Drugs. 2014;74:1127\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"hepatitis C virus, sustained virologic response, relapse, direct-acting antiviral, pangenotypic, genotype-specific, sofosbuvir, velpatasvir, glecaprevir, pibrentasvir","lastPublishedDoi":"10.21203/rs.3.rs-3876749/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3876749/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eEarly confirmation of sustained virologic response (SVR) or viral relapse after direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow-ups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA total of 1011 patients who achieved end-of-treatment virologic response, including 526 receiving pangenotypic DAAs, and 485 receiving genotype-specific DAAs, who had available off-treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off-treatment week 12 (SVR\u003csub\u003e12\u003c/sub\u003e) or viral relapse were included in the analysis. The positive predictive value (PPV) and negative predictive value (NPV) of SVR\u003csub\u003e4\u003c/sub\u003e to predict patients with SVR\u003csub\u003e12\u003c/sub\u003e or viral relapse were reported. Furthermore, we analyzed the concordance rate between SVR\u003csub\u003e12\u003c/sub\u003e and SVR\u003csub\u003e24\u003c/sub\u003e in 943 patients with available SVR\u003csub\u003e24\u003c/sub\u003e data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe PPV and NPV of SVR\u003csub\u003e4\u003c/sub\u003e to predict SVR\u003csub\u003e12\u003c/sub\u003e were 98.5% (95% confidence interval [CI]: 98.0%-98.9%) and 100% (95% CI: 66.4%-100%) in the entire population. The PPV of SVR\u003csub\u003e4\u003c/sub\u003e to predict SVR\u003csub\u003e12\u003c/sub\u003e in patients receiving pangenotypic DAAs was higher than those receiving genotype-specific DAAs (99.8% [95% CI: 98.9%-100%] versus 97.1% [95% CI: 96.2%-97.8%], p \u0026lt; 0.001). The NPVs of SVR\u003csub\u003e4\u003c/sub\u003e to predict viral relapse were 100%, regardless of type of DAAs. Moreover, the concordance rate between SVR\u003csub\u003e12\u003c/sub\u003e and SVR\u003csub\u003e24\u003c/sub\u003e was 100%.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eIn patients with HCV who are treated with pangenotypic DAAs, an off-treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR\u003csub\u003e \u003c/sub\u003eor viral relapse at off-treatment week 12.\u003c/p\u003e","manuscriptTitle":"Four weeks of off-treatment follow-up is sufficient to determine virologic responses at off-treatment week 12 in patients with hepatitis C virus infection receiving pangenotypic direct-acting antivirals","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-23 15:33:45","doi":"10.21203/rs.3.rs-3876749/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5cff0c99-100e-47e6-afd0-06b0685f7c35","owner":[],"postedDate":"January 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-05-24T03:55:12+00:00","versionOfRecord":{"articleIdentity":"rs-3876749","link":"https://doi.org/10.1002/jmv.29675","journal":{"identity":"journal-of-medical-virology","isVorOnly":true,"title":"Journal of Medical Virology"},"publishedOn":"2024-05-01 03:55:12","publishedOnDateReadable":"May 1st, 2024"},"versionCreatedAt":"2024-01-23 15:33:45","video":"","vorDoi":"10.1002/jmv.29675","vorDoiUrl":"https://doi.org/10.1002/jmv.29675","workflowStages":[]},"version":"v1","identity":"rs-3876749","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3876749","identity":"rs-3876749","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}