Efficacy of Sofosbuvir-Velpatasvir-Ribavirin Regimen for Retreatment of Chronic Hepatitis C in Patients with Prior DAA Failure: A Retrospective Study from a National Treatment Center

Efficacy of Sofosbuvir-Velpatasvir-Ribavirin Regimen for Retreatment of Chronic Hepatitis C in Patients with Prior DAA Failure: A Retrospective Study from a National Treatment Center | 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 Efficacy of Sofosbuvir-Velpatasvir-Ribavirin Regimen for Retreatment of Chronic Hepatitis C in Patients with Prior DAA Failure: A Retrospective Study from a National Treatment Center Sinku Singh, Sibangi Sengupta, Deepak Kumar, Kousik Mukherjee, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5480414/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction : Direct-acting antivirals (DAAs) are highly effective in treating HCV infection, but a small subset of patients may fail to achieve SVR12 and require further intervention. In resource-limited settings where second-line DAAs (such as SOF/VEL/VOX) may be unavailable, optimizing first-line treatments is essential. This study evaluated the efficacy (SVR12) of re-treatment regimen based on first-line DAAs (SOF/VEL) with ribavirin. Method: This retrospective study screened all viremic patients who attended the apex treatment center (ATC) between January 2019 and December 2023 and received DAAs as per the national Viral Hepatitis control program (NVHCP) guidelines. Patients who failed to achieve SVR12 were subsequently retreated with the available first-line regimen (SOF/VEL plus ribavirin). Results: A total of 1,814 viremic patients attended the apex treatment center (ATC). 1262 patients completed therapy. 1198 (94.9%) patients achieved SVR 12 and 64 patients (5.1%) failed to achieve SVR 12. Additionally, 41 patients with DAA failure were referred from treatment center (TC) and model treatment center (MTC) for evaluation. After further exclusions, 36 patients were enrolled, and 30 of them were offered retreatment. The majority of patients were male (64.5%) with a median age of 45 years (IQR; 19-68). Five patients were cirrhotic, while the remainder was non-cirrhotic. Baseline HCV RNA levels before the retreatment regimen was 87,882 IU/ml (IQR; 9,870-484,902). Most patients (96.6%) had genotype 3 HCV infection. Prior to retreatment, 27 patients had received a 12-week regimen of Sofosbuvir and Daclatasvir, while only three had been treated with the Sofosbuvir-Velpatasvir regimen. After retreatment with Sofosbuvir, Velpatasvir, and Ribavirin, 22 patients (73%) achieved SVR12. None of the patients experienced any adverse event. Conclusion: First-line DAAs are highly effective to treat naïve patients. In the absence of second-line options, retreatment with first-line DAAs (SOF/VEL plus ribavirin) is a viable alternative. HCV treatment failure HCV retreatment DAA Sofosbuvir Velpatasvir National Viral Hepatitis Control Program Figures Figure 1 Introduction Hepatitis C virus (HCV) infection contributes significantly to global morbidity and mortality, with an estimated 75 million people living with chronic HCV infection worldwide, according to the World Health Organization (WHO) [ 1 ]. In India, HCV prevalence is estimated at 0.3–0.5%, translating to a substantial number of infected individuals due to the country’s large population [ 2 ]. The WHO has set ambitious targets to eliminate viral hepatitis as a public health threat by 2030, aiming to diagnose 90% of chronic hepatitis cases and treat 80% of HCV patients [ 3 ]. Currently, however, only 9–20% of patients are aware of their virological status, and only a fraction of those affected are receiving treatment, underscoring an urgent need to improve access and ensure treatment for more individuals with chronic viral hepatitis. In response, the Government of India launched the National Viral Hepatitis Control Program (NVHCP), which seeks to scale up comprehensive screening, linkage to care, and treatment [ 4 ]. The program provides access to highly effective pan-genotypic drugs, including Sofosbuvir-Daclatasvir (SOF/DCV) and Sofosbuvir-Velpatasvir (SOF/VEL). According to NVHCP guidelines, a 12-week course of Sofosbuvir/Daclatasvir (SOF/DCV) is recommended for patients with non-cirrhotic HCV. A 12-week course of Sofosbuvir/Velpatasvir (SOF/VEL) is recommended for patients with compensated cirrhosis. For patients with decompensated cirrhosis, a 24-week course of SOF/VEL or a 12-week course of SOF/VEL/RBV is recommended [ 4 ]. Direct-Acting Antiviral (DAA) regimens generally demonstrate high efficacy, with cure rates between 90–98% [ 5 ], [ 6 ]. However, some factors—such as genotype 3 and cirrhosis—may reduce response rates [ 7 ]. In India, where genotype 3 is predominant, NVHCP does not recommend genotyping, applying a uniform treatment regimen for all patients. This approach could potentially lead to lower efficacy rates. Furthermore, with NVHCP's focus on broad screening, linkage to care, and decentralized treatment centers, a significant number of patients in real-world settings may not achieve a cure and may require re-treatment. However, a defined re-treatment regimen is currently lacking in NVHCP. International guidelines, such as those from the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD), recommend the Sofosbuvir-Velpatasvir-Voxilaprevir (SOF/VEL/VOX) combination as the re-treatment option of choice for patients who have not responded to previous DAA regimens[ 8 ],[ 9 ]. Unfortunately, this regimen is not available within NVHCP. There is limited data regarding efficacy of SOF/VEL with ribavirin as a retreatment regimen. A study from India by Goel et al. used SOF/VEL/RBV as a re-treatment regimen and achieved a sustained virological response (SVR) rate of 75% [ 10 ]. Therefore, in our study, we aimed to assess the outcomes of a re-treatment regimen based on available drugs, specifically SOF/VEL/RBV (SVR regimen). Materials and methods Study design, approvals and participants This retrospective study was conducted in the Outpatient Department (OPD) of the National Viral Hepatitis Control Program (NVHCP) at the Apex Treatment Centre (ATC), IPGME&R Kolkata, West-Bengal. The study protocol was adheres to the Declaration of Helsinki and received ethical clearance from the IPGME&R Research Oversight Committee, vide Memo No. IPGME&R/IEC/2024/0015. Written informed consent was obtained from patients who required a retreatment regimen. The study screened all HCV viremic patients who attended the NVHCP OPD from Jan 2019 to Dec 2023. After screening, study enrolled adults (age > 18 years) who have received first line DAA (SOF/DCV or SOF/VEL) regimen under the NVHCP program and failed to achieve SVR12. In addition to our center, we also received DAA failure patients from 32 treatment center (TC) and 2 Model Treatment Centre (MTC). Patients at high risk of reinfection after direct-acting antiviral (DAA) treatment failure were excluded from the study population. This exclusion applied to individuals on hemodialysis and those with hemoglobinopathies, as these patients frequently require transfusions of blood and blood products. Additionally, we excluded all patients who had percutaneous exposure to potential infection sources either during DAA therapy or before achieving sustained virological response at 12 weeks (SVR12). This included individuals with a history of intravenous drug use, hemodialysis, recent surgery, blood transfusions, or high-risk sexual behavior. Patients who were non-compliant or received inadequate doses of DAA were also excluded from the study population. Assessment: Upon enrollment, demography and anthropometry data were meticulously recorded. This included details such as age, gender, body weight and other relevant demographic information. Furthermore, the study documented the participants' previous treatment regimens including duration and adherence to therapy. From data base all essential Laboratory investigations including complete blood count (CBC), liver function tests (LFT), renal function tests (RFT) were recorded. Additional information comprised HCV RNA levels, abdominal ultrasonography. Geno-typing was restricted only in patients who needed re-treatment regimen. Before retreatment fibrosis was assessed by transient elastography, APRI and FIB4. Viral load estimation and genotyping HCV RNA concentrations in serum or EDTA plasma were quantified using the COBAS AmpliPrep/COBAS TaqMan HCV Quantitative test (version 2.0; ThermoFisher Scientific, Waltham, MA, USA; lower limit of quantification 15 IU/mL) or the Abbott m2000 system (Abbott, Chicago, IL, USA; lower limit of quantification 12 IU/mL). HCV genotype was determined by the Versant HCV Genotype Inno-LiPA Assay v2.0 (Siemens Healthcare Diagnostics, Tarrytown, NY, USA). Liver stiffness measurement (LSM) Liver stiffness was measured by Transient elastography (FibroScan, Echosens, Paris, France) using a medium probe. LSM was performed by the study investigators. Ten valid measurements were obtained and reported as a median value in kilo-Pascals (kPa). Only measurements with at least ten valid acquisitions, a success rate > 60%, and an interquartile range over median (IQR/M) value 12.5 kPa for cirrhosis and > 8.6 kPa for advanced fibrosis [ 11 ]. Retreatment regimen: At present NVHCP provides only fist line DAA. Ribavirin is available only in apex treatment center (ATC). All patients received Sofosbubir-Velpatasvir (400/100 mg) fixed dose combination with weight based Ribavirin for 24 weeks. End point The primary endpoint was the proportion of DAA failure patients who did not achieve SVR12 with retreatment regimen based upon combination of SOF/VEL with ribavirin. Statistical analysis All data were entered into a Microsoft Excel Spreadsheet. Data analysis was carried out using appropriate statistical software using SPSS 28-2021 version. The results were expressed as percentage, Median (IQR). Results Patient population Between Jan 2019 and December 2023, our center registered 1,814 HCV infected patients with detectable viremia, of whom 1347 patients were offered DAA. Of these 1262 patients completed therapy. 1198 (94.9%) patients achieved SVR 12 and 68 patients (5.1%) failed to achieve SVR 12 [figure 1]. In addition, we received 41 patients who had experienced treatment failure from other treatment centers (TC) or model treatment centers (MTC). After excluding 69 patients, we included 36 patients in our study; however, 6 patients could not be tracked for further evaluation. Therefore, the study included 30 patients who were offered a retreatment regimen [figure 1]. Detailed patient characteristics are provided in Table 1 . Most patients were male (64.5%), with a median age of 45 years. All patients received treatment according to NVHCP guidelines [ 4 ]. Among the study cohort, 25 patients were non-cirrhotic, 4 had compensated cirrhosis, and 1 had decompensated cirrhosis [Table 1 ]. The median viral load before first-line treatment was 324,115 IU/ml (IQR: 20,464–1,454,988), and before retreatment, it was 87,882 IU/ml (IQR: 9,870–484,909). The genotype distribution was as follows: genotype 3a – 63.3% (n = 19), genotype 3b – 33.3% (n = 10), and genotype 1a – 3.3% (n = 1) [Table 1 ]. Table 1 Base line demographic and clinical characteristic of treatment failure patients Total patients, n = 30 Age 45(19–68) Sex (Male) 20(64.5%) Body weight(kg) 56(50.7–65.7) Laboratory parameters HB(g/dL) 10.0(9-11.3) Platelet 175(160–238) Serum total Bilirubin (mg/dL) 0.97(0.73–1.5) ALT((IU/L) 45((29-79.7) AST(IU/L) 47(32.5–94.7) Albumin(g/dL) 3.7(2.9–4.3) Creatinine(mg/dL) 0.98(0.79–1.1) Non-invasive markers of Fibrosis APRI 0.65(0.40–0.90) FIB4 1.42(0.88–2.21) LSM 7.35(5.0-8.3) Viral load HCV RNA in treatment naïve patients(IU/ml) 324115(20464-1454988) HCV RNA before re –treatment(IU/ml) 87882(9870-484902) Geno-type G 3a 19(63.3) G 3b 10(33.3) G 1a 1(3.03) Disease phenotype Non Cirrhotic 25(83.3) Compensated cirrhotic 4 (13.3) Decompensated cirrhosis 1(3.3) First line regimen Sof + Daclatasvir x12 weeks 27(90) Sof + Velpatasvir x12 weeks 2(6.6) Sof + Velpatasvir x24 weeks 1(3.3) Data are expressed as median and IQR or number (%) unless otherwise specified Efficacy of retreatment regimen All patients received a re-treatment regimen based on fixed dose combination of Sofosbuvir-Velpatasvir and weight based ribavirin for 24 weeks. Twenty-two patients (73.3%) achieved SVR12, while 8 (26.6%) did not achieve SVR12 [Figure 1]. No major adverse events were reported. Of the 8 patients who failed to achieve SVR12, 5 were non-cirrhotic, and 3 had cirrhosis [Table 1 ]. The median pre-retreatment HCV RNA for treatment failures was 1,422,070 IU/mL (IQR: 361916–6515695) [Table 2 ]. Detailed characteristics of individual patients who did not achieve SVR with the re-treatment regimen are summarized in Table 2 . As NVHCP does not provide third-line therapy, no patients received further treatment. Table 2 Characteristics of patients who did not respond to retreatment regimen serial no age sex APRI FIB4 LSM Geno-type Disease phenotype Viral load before Retreatment(IU/Ml) Previous treatment 1 49 M 0.9 2.89 44.1 G3a Decompensated cirrhosis 853726 SOF/VELX 24 week 2 24 M 0.9 2.56 5.1 G3a Non cirrhotic 123121 SOF/DACX12 week 3 38 F 0.5 0.51 4.5 G1b Non cirrhotic 600711 SOF/DACX12 week 4 28 M 3.3 0.88 26.8 G3b Compensated cirrhotic 1990414 SOF/VELX 24 week 5 46 M 1.6 0.85 5.0 G3a Non cirrhotic 7834555 SOF/DACX12 week 6 68 M 0.7 1.76 22.3 G3a Compensated cirrhotic 7890 SOF/DACX12 week 7 58 M 0.4 0.89 5.3 G3b Non cirrhotic 5581359 SOF/DACX12 week 8 34 F 0.3 0.80 7.4 G3a Non cirrhotic 7450031 SOF/DACX12 week Discussion Chronic viral hepatitis is a significant public health issue [ 3 ]. To reduce its associated mortality and morbidity, many countries have launched national programs to address viral hepatitis. The Government of India has introduced its own national program, providing drugs and diagnostic services free of cost [ 4 ]. Direct-Acting Antivirals (DAAs) have real-world efficacy rates of 90–98%, yet some patients do not achieve a sustained virological response (SVR). Currently, the National Viral Hepatitis Control Program (NVHCP) does not define a standard re-treatment regimen, offers a limited selection of drugs, and does not require genotyping before treatment. Patients who experience treatment failure are referred to apex centers for advanced care. To improve the program’s effectiveness, it is crucial to understand the rate of treatment failure and identify optimal re-treatment regimens. In our single-center retrospective study, we found an overall virological failure rate of 5.0%. A large-scale study from India by Dhiman et al. reported virological failure is 8% [ 5 ]. The combination of voxilaprevir, velpatasvir, and sofosbuvir (VOX/VEL/SOF) is the preferred second-line treatment for patients with prior DAA failures, achieving viral eradication rates above 95% [ 12 ]. However, VOX/VEL/SOF is currently unavailable in the NVHCP, which limits re-treatment options. Data on treatment failures within the national program also remain limited. Given the ethical imperative to provide re-treatment, we included 30 patients with prior treatment failure and treated them with a 24-week regimen of sofosbuvir, velpatasvir, and ribavirin (SOF/VEL/RBV). 73% of these patients achieved SVR12, which is consistent with the findings of a study by Amit et al., which reported an SVR12 rate of 75% for the same regimen [ 10 ]. Another retrospective study demonstrated an SVR12 rate of 100% with a SOF/VEL-based regimen, with or without ribavirin [ 13 ]. So, our study reflects similar trends, though our efficacy rate is slightly lower. Our findings underscore the potential benefit of the SOF/VEL/RBV regimen for optimizing treatment outcomes. Limitations: This retrospective, single-center study may not fully represent the outcomes of the entire national program. Although the NVHCP recommends SOF/VEL for compensated cirrhosis, one cirrhotic patient received SOF/DCV as the first-line treatment. Additionally, while patients with treatment failures from other centers were included, SVR12 data from those centers were unavailable. The small sample size of treatment-failure patients also limited our ability to identify predictors of non-response. Conclusion This single-center retrospective study under NVHCP has shown that Direct-Acting Antivirals (DAAs) are highly effective in real-life scenarios. The re-treatment regimen with Sofosbuvir, Velpatasvir, and ribavirin for 24 weeks achieved a sustained virological response (SVR) at 12 weeks in 73% of cases. This regimen may be considered a second-line option. In the future, the program should develop a management protocol for patients with DAA failure, including the availability of the Voxilaprevir, Sofosbuvir, and Velpatasvir regimen. Abbreviations NVHCP: National Viral Hepatitis Control Program; TC: Treatment Centre; MTC: Model treatment center; ATC: Apex treatment center; TE: Transient elastography; kPa: kilo-Pascals; LS: Liver stiffness; SVR12: sustained virological response 12; DAA: direct acting-antivirals; APRI score: aspartate aminotransferase (AST)-to-platelet ratio index (APRI) score;FIB4 score: Fibrosis -4 (FIB-4) score; WHO: the World Health Organization; IDU: iv drug user; SOF:Sofosbuvir; VEL:Velpatasvir; VOX:Voxilaprevir; DCV:Daclatasvir; RBV:Ribavirin Declarations Authorship contribution credit statement: Concept: Sk. Mahiuddin Ahammed, Sinku Singh, Sibangi Sengupta, Deepak Kumar, Kousik Mukherjee, Abdulla MD Hasan, Provash Sadhukhan, Design: Sk. Mahiuddin Ahammed, Sinku Singh, Sibangi Sengupta, Deepak Kumar Data collection: Sinku Singh, Sibangi Sengupta, Deepak Kumar, Kousik Mukherjee, Abdulla MD Hasan, Provash Sadhukhan, Data interpretation: Sk. Mahiuddin Ahammed, Provash Sadhukhan, First draft: Sk. Mahiuddin Ahammed, Sinku Singh, Sibangi Sengupta, Deepak Kumar, Kousik Mukherjee, Abdulla MD Hasan, Provash Sadhukhan Final draft approval: Sk. Mahiuddin Ahammed, Sinku Singh, Sibangi Sengupta, Deepak Kumar, Kousik Mukherjee, Abdulla MD Hasan, Provash Sadhukhan, Acknowledgment: We gratefully acknowledge all participants and their families. Conflict of interest : none Funding: None Ethics approval and consent to participate The study protocol was adheres to the Declaration of Helsinki and received ethical clearance from the IPGME&R Research Oversight Committee, vide Memo No. IPGME&R/IEC/2024/0015. Written informed consent was obtained from patients who required a retreatment regimen References World Health Organization. WHO Global Hepatitis Report. 2017. Goel A, Rewari BB, Sharma M, et al. Sero-prevalence and burden of hepatitis C virus infection in WHO South-East Asia Region: A systematic review. J Gastroenterol Hepatol. 2022;37(6):964–72. 10.1111/jgh.15827 . Epub 2022 Mar 18. PMID: 35263807. Andrea L, Cox, Manal H, El-Sayed et al. Progress towards elimination goals for viral hepatitis: Nature review, gastroenterology, and hepatology: Vol.17. sep 2020. 534–541. National Guidelines for Diagnosis & Management of Viral Hepatitis. 2018. Hepatitis C Infection. https://main.mohfw.gov.in/documents/program-guidelines . Last accessed 08 Nov. 2016. Dhiman RK, Grover GS, Premkumar M, et al. Decentralized care with generic direct-acting antivirals in the management of chronic hepatitis C in a public health care setting. J Hepatol. 2019;71:1076–85. Chang KC, Tung SY, Wei KL, et al. Real-world efficacy and safety of pangenotypic direct-acting antivirals against hepatitis C virus infection in Taiwan. Sci Rep. 2021;11(1):13543. 10.1038/s41598-021-93095-x . PMID: 34188161; PMCID: PMC8241842. Ampuero J, Romero-Gomez M, Reddy KR. Review article: HCV genotype 3 - the new treatment challenge. Aliment Pharmacol Ther. 2014;39:686–98. European Association for the Study of the Liver. J Hepatol. 2020;73(5):1170–218. 10.1016/j.jhep.2020.08.018 . Bhattacharya D, Aronsohn A, Price J et al. AASLD-IDSA HCV Guidance Panel. Hepatitis C Guidance 2023 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Clin Infect Dis. 2023 May 25:ciad319. 10.1093/cid/ciad319 . Epub ahead of print. PMID: 37229695. Goel A, Katiyar H, Mayank, Clin Exp J et al. Hepatol. 2023 Sep-Oct;13(5):736–41. 10.1016/j.jceh.2023.03.007 . Epub 2023 Mar 24. PMID: 37693269; PMCID: PMC10482998. Anstee QM, Castera L, Loomba R. Impact of non-invasive biomarkers on hepatology practice: Past, present and future. J Hepatol. 2022;76(6):1362–1378. 10.1016/j.jhep.2022.03.026 . PMID: 35589256. Bourlière M, Gordon SC, Flamm SL et al. Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection. N Engl J Med. 2017;376(22):2134–2146. 10.1056/NEJMoa1613512 . PMID: 28564569. Elhence A, Singh A, Anand A, et al. Real-world re-treatment outcomes of direct-acting antiviral therapy failure in patients with chronic hepatitis C. J Med Virol. 2021;93(8):4982–91. 10.1002/jmv.26971 . Epub 2021 Apr 13. PMID: 33783006. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted 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-5480414","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":380973328,"identity":"a49a3a8e-0644-48d1-98d6-5f156ae21618","order_by":0,"name":"Sinku Singh","email":"","orcid":"","institution":"Institute of Post Graduate Medical Education and Research","correspondingAuthor":false,"prefix":"","firstName":"Sinku","middleName":"","lastName":"Singh","suffix":""},{"id":380973329,"identity":"cb888c00-225a-408d-9146-017da71d00e1","order_by":1,"name":"Sibangi Sengupta","email":"","orcid":"","institution":"Institute of Post Graduate Medical 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13:25:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1361072,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5480414/v1/b5739aa2-2f1c-4193-8f0c-dd1a0ec1cef0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy of Sofosbuvir-Velpatasvir-Ribavirin Regimen for Retreatment of Chronic Hepatitis C in Patients with Prior DAA Failure: A Retrospective Study from a National Treatment Center","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHepatitis C virus (HCV) infection contributes significantly to global morbidity and mortality, with an estimated 75\u0026nbsp;million people living with chronic HCV infection worldwide, according to the World Health Organization (WHO) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In India, HCV prevalence is estimated at 0.3\u0026ndash;0.5%, translating to a substantial number of infected individuals due to the country\u0026rsquo;s large population [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe WHO has set ambitious targets to eliminate viral hepatitis as a public health threat by 2030, aiming to diagnose 90% of chronic hepatitis cases and treat 80% of HCV patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Currently, however, only 9\u0026ndash;20% of patients are aware of their virological status, and only a fraction of those affected are receiving treatment, underscoring an urgent need to improve access and ensure treatment for more individuals with chronic viral hepatitis.\u003c/p\u003e \u003cp\u003eIn response, the Government of India launched the National Viral Hepatitis Control Program (NVHCP), which seeks to scale up comprehensive screening, linkage to care, and treatment [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The program provides access to highly effective pan-genotypic drugs, including Sofosbuvir-Daclatasvir (SOF/DCV) and Sofosbuvir-Velpatasvir (SOF/VEL). According to NVHCP guidelines, a 12-week course of Sofosbuvir/Daclatasvir (SOF/DCV) is recommended for patients with non-cirrhotic HCV. A 12-week course of Sofosbuvir/Velpatasvir (SOF/VEL) is recommended for patients with compensated cirrhosis. For patients with decompensated cirrhosis, a 24-week course of SOF/VEL or a 12-week course of SOF/VEL/RBV is recommended [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDirect-Acting Antiviral (DAA) regimens generally demonstrate high efficacy, with cure rates between 90\u0026ndash;98% [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, some factors\u0026mdash;such as genotype 3 and cirrhosis\u0026mdash;may reduce response rates [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In India, where genotype 3 is predominant, NVHCP does not recommend genotyping, applying a uniform treatment regimen for all patients. This approach could potentially lead to lower efficacy rates. Furthermore, with NVHCP's focus on broad screening, linkage to care, and decentralized treatment centers, a significant number of patients in real-world settings may not achieve a cure and may require re-treatment.\u003c/p\u003e \u003cp\u003eHowever, a defined re-treatment regimen is currently lacking in NVHCP. International guidelines, such as those from the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD), recommend the Sofosbuvir-Velpatasvir-Voxilaprevir (SOF/VEL/VOX) combination as the re-treatment option of choice for patients who have not responded to previous DAA regimens[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e],[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Unfortunately, this regimen is not available within NVHCP. There is limited data regarding efficacy of SOF/VEL with ribavirin as a retreatment regimen. A study from India by Goel et al. used SOF/VEL/RBV as a re-treatment regimen and achieved a sustained virological response (SVR) rate of 75% [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Therefore, in our study, we aimed to assess the outcomes of a re-treatment regimen based on available drugs, specifically SOF/VEL/RBV (SVR regimen).\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design, approvals and participants\u003c/h2\u003e \u003cp\u003eThis retrospective study was conducted in the Outpatient Department (OPD) of the National Viral Hepatitis Control Program (NVHCP) at the Apex Treatment Centre (ATC), IPGME\u0026amp;R Kolkata, West-Bengal. The study protocol was adheres to the Declaration of Helsinki and received ethical clearance from the IPGME\u0026amp;R Research Oversight Committee, vide Memo No. IPGME\u0026amp;R/IEC/2024/0015. Written informed consent was obtained from patients who required a retreatment regimen.\u003c/p\u003e \u003cp\u003eThe study screened all HCV viremic patients who attended the NVHCP OPD from Jan 2019 to Dec 2023. After screening, study enrolled adults (age\u0026thinsp;\u0026gt;\u0026thinsp;18 years) who have received first line DAA (SOF/DCV or SOF/VEL) regimen under the NVHCP program and failed to achieve SVR12. In addition to our center, we also received DAA failure patients from 32 treatment center (TC) and 2 Model Treatment Centre (MTC).\u003c/p\u003e \u003cp\u003ePatients at high risk of reinfection after direct-acting antiviral (DAA) treatment failure were excluded from the study population. This exclusion applied to individuals on hemodialysis and those with hemoglobinopathies, as these patients frequently require transfusions of blood and blood products. Additionally, we excluded all patients who had percutaneous exposure to potential infection sources either during DAA therapy or before achieving sustained virological response at 12 weeks (SVR12). This included individuals with a history of intravenous drug use, hemodialysis, recent surgery, blood transfusions, or high-risk sexual behavior. Patients who were non-compliant or received inadequate doses of DAA were also excluded from the study population.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAssessment:\u003c/h3\u003e\n\u003cp\u003eUpon enrollment, demography and anthropometry data were meticulously recorded. This included details such as age, gender, body weight and other relevant demographic information. Furthermore, the study documented the participants' previous treatment regimens including duration and adherence to therapy. From data base all essential Laboratory investigations including complete blood count (CBC), liver function tests (LFT), renal function tests (RFT) were recorded. Additional information comprised HCV RNA levels, abdominal ultrasonography. Geno-typing was restricted only in patients who needed re-treatment regimen. Before retreatment fibrosis was assessed by transient elastography, APRI and FIB4.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eViral load estimation and genotyping\u003c/strong\u003e \u003cp\u003eHCV RNA concentrations in serum or EDTA plasma were quantified using the COBAS AmpliPrep/COBAS TaqMan HCV Quantitative test (version 2.0; ThermoFisher Scientific, Waltham, MA, USA; lower limit of quantification 15 IU/mL) or the Abbott m2000 system (Abbott, Chicago, IL, USA; lower limit of quantification 12 IU/mL). HCV genotype was determined by the Versant HCV Genotype Inno-LiPA Assay v2.0 (Siemens Healthcare Diagnostics, Tarrytown, NY, USA).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eLiver stiffness measurement (LSM)\u003c/strong\u003e \u003cp\u003eLiver stiffness was measured by Transient elastography (FibroScan, Echosens, Paris, France) using a medium probe. LSM was performed by the study investigators. Ten valid measurements were obtained and reported as a median value in kilo-Pascals (kPa). Only measurements with at least ten valid acquisitions, a success rate\u0026thinsp;\u0026gt;\u0026thinsp;60%, and an interquartile range over median (IQR/M) value\u0026thinsp;\u0026lt;\u0026thinsp;30% were included in the study. The cut-offs used were \u0026gt;\u0026thinsp;12.5 kPa for cirrhosis and \u0026gt;\u0026thinsp;8.6 kPa for advanced fibrosis [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003c/p\u003e\n\u003ch3\u003eRetreatment regimen:\u003c/h3\u003e\n\u003cp\u003eAt present NVHCP provides only fist line DAA. Ribavirin is available only in apex treatment center (ATC). All patients received Sofosbubir-Velpatasvir (400/100 mg) fixed dose combination with weight based Ribavirin for 24 weeks.\u003c/p\u003e\n\u003ch3\u003eEnd point\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint was the proportion of DAA failure patients who did not achieve SVR12 with retreatment regimen based upon combination of SOF/VEL with ribavirin.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll data were entered into a Microsoft Excel Spreadsheet. Data analysis was carried out using appropriate statistical software using SPSS 28-2021 version. The results were expressed as percentage, Median (IQR).\u003c/p\u003e \u003c/div\u003e "},{"header":"Results","content":"\u003cdiv id=\"Sec8\" type=\"Results\" class=\"Section2\"\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003ePatient population\u003c/h2\u003e \u003cp\u003eBetween Jan 2019 and December 2023, our center registered 1,814 HCV infected patients with detectable viremia, of whom 1347 patients were offered DAA. Of these 1262 patients completed therapy. 1198 (94.9%) patients achieved SVR 12 and 68 patients (5.1%) failed to achieve SVR 12 [figure 1]. In addition, we received 41 patients who had experienced treatment failure from other treatment centers (TC) or model treatment centers (MTC). After excluding 69 patients, we included 36 patients in our study; however, 6 patients could not be tracked for further evaluation. Therefore, the study included 30 patients who were offered a retreatment regimen [figure 1]. Detailed patient characteristics are provided in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Most patients were male (64.5%), with a median age of 45 years. All patients received treatment according to NVHCP guidelines [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Among the study cohort, 25 patients were non-cirrhotic, 4 had compensated cirrhosis, and 1 had decompensated cirrhosis [Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e]. The median viral load before first-line treatment was 324,115 IU/ml (IQR: 20,464\u0026ndash;1,454,988), and before retreatment, it was 87,882 IU/ml (IQR: 9,870\u0026ndash;484,909). The genotype distribution was as follows: genotype 3a \u0026ndash; 63.3% (n\u0026thinsp;=\u0026thinsp;19), genotype 3b \u0026ndash; 33.3% (n\u0026thinsp;=\u0026thinsp;10), and genotype 1a \u0026ndash; 3.3% (n\u0026thinsp;=\u0026thinsp;1) [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\u003eBase line demographic and clinical characteristic of treatment failure patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal patients, n\u0026thinsp;=\u0026thinsp;30\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45(19\u0026ndash;68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (Male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20(64.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody weight(kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56(50.7\u0026ndash;65.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLaboratory parameters\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHB(g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.0(9-11.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e175(160\u0026ndash;238)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum total Bilirubin (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.97(0.73\u0026ndash;1.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT((IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45((29-79.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST(IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47(32.5\u0026ndash;94.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin(g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.7(2.9\u0026ndash;4.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine(mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.98(0.79\u0026ndash;1.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNon-invasive markers of Fibrosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPRI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.65(0.40\u0026ndash;0.90)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFIB4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.42(0.88\u0026ndash;2.21)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLSM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.35(5.0-8.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eViral load\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHCV RNA in treatment na\u0026iuml;ve patients(IU/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e324115(20464-1454988)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHCV RNA before re \u0026ndash;treatment(IU/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e87882(9870-484902)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGeno-type\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eG 3a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(63.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eG 3b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eG 1a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(3.03)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDisease phenotype\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon Cirrhotic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25(83.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCompensated cirrhotic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (13.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDecompensated cirrhosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFirst line regimen\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSof\u0026thinsp;+\u0026thinsp;Daclatasvir x12 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27(90)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSof\u0026thinsp;+\u0026thinsp;Velpatasvir x12 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(6.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSof\u0026thinsp;+\u0026thinsp;Velpatasvir x24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eData are expressed as median and IQR or number (%) unless otherwise specified\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e\n\u003ch3\u003eEfficacy of retreatment regimen\u003c/h3\u003e\n\u003cp\u003eAll patients received a re-treatment regimen based on fixed dose combination of Sofosbuvir-Velpatasvir and weight based ribavirin for 24 weeks. Twenty-two patients (73.3%) achieved SVR12, while 8 (26.6%) did not achieve SVR12 [Figure 1]. No major adverse events were reported. Of the 8 patients who failed to achieve SVR12, 5 were non-cirrhotic, and 3 had cirrhosis [Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e]. The median pre-retreatment HCV RNA for treatment failures was 1,422,070 IU/mL (IQR: 361916\u0026ndash;6515695) [Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e]. Detailed characteristics of individual patients who did not achieve SVR with the re-treatment regimen are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. As NVHCP does not provide third-line therapy, no patients received further treatment.\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\u003eCharacteristics of patients who did not respond to retreatment regimen\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=\"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=\"char\" char=\".\" 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=\"char\" char=\".\" 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=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eserial no\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003esex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAPRI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFIB4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLSM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGeno-type\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eDisease phenotype\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eViral load before Retreatment(IU/Ml)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePrevious treatment\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e44.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eG3a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eDecompensated cirrhosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e853726\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSOF/VELX 24 week\u003c/p\u003e \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\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eG3a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNon cirrhotic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e123121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSOF/DACX12 week\u003c/p\u003e \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\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eG1b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNon cirrhotic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e600711\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSOF/DACX12 week\u003c/p\u003e \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\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e26.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eG3b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCompensated cirrhotic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1990414\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSOF/VELX 24 week\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eG3a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNon cirrhotic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e7834555\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSOF/DACX12 week\u003c/p\u003e \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\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e22.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eG3a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCompensated cirrhotic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e7890\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSOF/DACX12 week\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eG3b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNon cirrhotic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e5581359\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSOF/DACX12 week\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\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eG3a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNon cirrhotic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e7450031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSOF/DACX12 week\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eChronic viral hepatitis is a significant public health issue [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. To reduce its associated mortality and morbidity, many countries have launched national programs to address viral hepatitis. The Government of India has introduced its own national program, providing drugs and diagnostic services free of cost [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDirect-Acting Antivirals (DAAs) have real-world efficacy rates of 90\u0026ndash;98%, yet some patients do not achieve a sustained virological response (SVR). Currently, the National Viral Hepatitis Control Program (NVHCP) does not define a standard re-treatment regimen, offers a limited selection of drugs, and does not require genotyping before treatment. Patients who experience treatment failure are referred to apex centers for advanced care.\u003c/p\u003e \u003cp\u003eTo improve the program\u0026rsquo;s effectiveness, it is crucial to understand the rate of treatment failure and identify optimal re-treatment regimens. In our single-center retrospective study, we found an overall virological failure rate of 5.0%. A large-scale study from India by Dhiman et al. reported virological failure is 8% [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The combination of voxilaprevir, velpatasvir, and sofosbuvir (VOX/VEL/SOF) is the preferred second-line treatment for patients with prior DAA failures, achieving viral eradication rates above 95% [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, VOX/VEL/SOF is currently unavailable in the NVHCP, which limits re-treatment options. Data on treatment failures within the national program also remain limited.\u003c/p\u003e \u003cp\u003e Given the ethical imperative to provide re-treatment, we included 30 patients with prior treatment failure and treated them with a 24-week regimen of sofosbuvir, velpatasvir, and ribavirin (SOF/VEL/RBV). 73% of these patients achieved SVR12, which is consistent with the findings of a study by Amit et al., which reported an SVR12 rate of 75% for the same regimen [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Another retrospective study demonstrated an SVR12 rate of 100% with a SOF/VEL-based regimen, with or without ribavirin [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. So, our study reflects similar trends, though our efficacy rate is slightly lower.\u003c/p\u003e \u003cp\u003eOur findings underscore the potential benefit of the SOF/VEL/RBV regimen for optimizing treatment outcomes.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eLimitations:\u003c/h2\u003e \u003cp\u003eThis retrospective, single-center study may not fully represent the outcomes of the entire national program. Although the NVHCP recommends SOF/VEL for compensated cirrhosis, one cirrhotic patient received SOF/DCV as the first-line treatment. Additionally, while patients with treatment failures from other centers were included, SVR12 data from those centers were unavailable. The small sample size of treatment-failure patients also limited our ability to identify predictors of non-response.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis single-center retrospective study under NVHCP has shown that Direct-Acting Antivirals (DAAs) are highly effective in real-life scenarios. The re-treatment regimen with Sofosbuvir, Velpatasvir, and ribavirin for 24 weeks achieved a sustained virological response (SVR) at 12 weeks in 73% of cases. This regimen may be considered a second-line option. In the future, the program should develop a management protocol for patients with DAA failure, including the availability of the Voxilaprevir, Sofosbuvir, and Velpatasvir regimen.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003eNVHCP: National Viral Hepatitis Control Program; TC: Treatment Centre; MTC: Model treatment center; ATC: Apex treatment center; TE: Transient elastography; kPa: kilo-Pascals; LS: Liver stiffness; SVR12: sustained virological response 12; DAA: direct acting-antivirals; APRI score: aspartate aminotransferase (AST)-to-platelet ratio index (APRI) score;FIB4 score: Fibrosis -4 (FIB-4) score; WHO: the World Health Organization; IDU: iv drug user;\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eSOF:Sofosbuvir; VEL:Velpatasvir; VOX:Voxilaprevir; DCV:Daclatasvir; RBV:Ribavirin\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthorship contribution credit statement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConcept: Sk. Mahiuddin Ahammed,\u0026nbsp;Sinku Singh, Sibangi Sengupta, Deepak Kumar, Kousik Mukherjee, Abdulla MD Hasan, Provash Sadhukhan,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDesign: Sk. Mahiuddin Ahammed, Sinku Singh, Sibangi Sengupta, Deepak Kumar\u003c/p\u003e\n\u003cp\u003eData collection: Sinku Singh, Sibangi Sengupta, Deepak Kumar, Kousik Mukherjee, Abdulla MD Hasan,\u0026nbsp;Provash Sadhukhan,\u003c/p\u003e\n\u003cp\u003eData interpretation: Sk. Mahiuddin Ahammed,\u0026nbsp;Provash Sadhukhan,\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;First draft:\u0026nbsp;Sk. Mahiuddin Ahammed, Sinku Singh, Sibangi Sengupta, Deepak Kumar, Kousik Mukherjee, Abdulla MD Hasan, Provash Sadhukhan\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Final draft approval: Sk. Mahiuddin Ahammed, Sinku Singh, Sibangi Sengupta, Deepak Kumar, Kousik Mukherjee, Abdulla MD Hasan, Provash Sadhukhan,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment:\u003c/strong\u003e We gratefully acknowledge all participants and their families.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e: none\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was adheres to the Declaration of Helsinki and received ethical clearance from the IPGME\u0026amp;R Research Oversight Committee, vide Memo No. IPGME\u0026amp;R/IEC/2024/0015. Written informed consent was obtained from patients who required a retreatment regimen\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWorld Health Organization. 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Hepatitis C Infection. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://main.mohfw.gov.in/documents/program-guidelines\u003c/span\u003e\u003cspan address=\"https://main.mohfw.gov.in/documents/program-guidelines\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Last accessed 08 Nov. 2016.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDhiman RK, Grover GS, Premkumar M, et al. Decentralized care with generic direct-acting antivirals in the management of chronic hepatitis C in a public health care setting. J Hepatol. 2019;71:1076\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang KC, Tung SY, Wei KL, et al. Real-world efficacy and safety of pangenotypic direct-acting antivirals against hepatitis C virus infection in Taiwan. Sci Rep. 2021;11(1):13543. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41598-021-93095-x\u003c/span\u003e\u003cspan address=\"10.1038/s41598-021-93095-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 34188161; PMCID: PMC8241842.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmpuero J, Romero-Gomez M, Reddy KR. Review article: HCV genotype 3 - the new treatment challenge. Aliment Pharmacol Ther. 2014;39:686\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEuropean Association for the Study of the Liver. 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Hepatol. 2023 Sep-Oct;13(5):736\u0026ndash;41. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jceh.2023.03.007\u003c/span\u003e\u003cspan address=\"10.1016/j.jceh.2023.03.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2023 Mar 24. PMID: 37693269; PMCID: PMC10482998.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAnstee QM, Castera L, Loomba R. Impact of non-invasive biomarkers on hepatology practice: Past, present and future. J Hepatol. 2022;76(6):1362\u0026ndash;1378. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jhep.2022.03.026\u003c/span\u003e\u003cspan address=\"10.1016/j.jhep.2022.03.026\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 35589256.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBourli\u0026egrave;re M, Gordon SC, Flamm SL et al. Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection. N Engl J Med. 2017;376(22):2134\u0026ndash;2146. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa1613512\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa1613512\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 28564569.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElhence A, Singh A, Anand A, et al. Real-world re-treatment outcomes of direct-acting antiviral therapy failure in patients with chronic hepatitis C. J Med Virol. 2021;93(8):4982\u0026ndash;91. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/jmv.26971\u003c/span\u003e\u003cspan address=\"10.1002/jmv.26971\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2021 Apr 13. PMID: 33783006.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"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":"HCV treatment failure, HCV retreatment, DAA, Sofosbuvir, Velpatasvir, National Viral Hepatitis Control Program","lastPublishedDoi":"10.21203/rs.3.rs-5480414/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5480414/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e: Direct-acting antivirals (DAAs) are highly effective in treating HCV infection, but a small subset of patients may fail to achieve SVR12 and require further intervention. In resource-limited settings where second-line DAAs (such as SOF/VEL/VOX) may be unavailable, optimizing first-line treatments is essential. This study evaluated the efficacy (SVR12) of re-treatment regimen based on first-line DAAs (SOF/VEL) with ribavirin.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod: \u003c/strong\u003eThis retrospective study screened all viremic patients who attended the apex treatment center (ATC) between January 2019 and December 2023 and received DAAs as per the national Viral Hepatitis control program (NVHCP) guidelines. Patients who failed to achieve SVR12 were subsequently retreated with the available first-line regimen (SOF/VEL plus ribavirin).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eA total of 1,814 viremic patients attended the apex treatment center (ATC). 1262 patients completed therapy. 1198 (94.9%) patients achieved SVR 12 and 64 patients (5.1%) failed to achieve SVR 12. Additionally, 41 patients with DAA failure were referred from treatment center (TC) and model treatment center (MTC) for evaluation. After further exclusions, 36 patients were enrolled, and 30 of them were offered retreatment. The majority of patients were male (64.5%) with a median age of 45 years (IQR; 19-68). Five patients were cirrhotic, while the remainder was non-cirrhotic. Baseline HCV RNA levels before the retreatment regimen was 87,882 IU/ml (IQR; 9,870-484,902). Most patients (96.6%) had genotype 3 HCV infection. Prior to retreatment, 27 patients had received a 12-week regimen of Sofosbuvir and Daclatasvir, while only three had been treated with the Sofosbuvir-Velpatasvir regimen. After retreatment with Sofosbuvir, Velpatasvir, and Ribavirin, 22 patients (73%) achieved SVR12. None of the patients experienced any adverse event.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eFirst-line DAAs are highly effective to treat naïve patients. In the absence of second-line options, retreatment with first-line DAAs (SOF/VEL plus ribavirin) is a viable alternative.\u003c/p\u003e","manuscriptTitle":"Efficacy of Sofosbuvir-Velpatasvir-Ribavirin Regimen for Retreatment of Chronic Hepatitis C in Patients with Prior DAA Failure: A Retrospective Study from a National Treatment Center","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-19 12:58:36","doi":"10.21203/rs.3.rs-5480414/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":"e8b8fa73-2d70-4154-a9e2-03c92c8bbead","owner":[],"postedDate":"December 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-10T13:25:30+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-19 12:58:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5480414","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5480414","identity":"rs-5480414","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}