Reevaluating Antiviral Thresholds in HBV DNA-Negative Inactive HBsAg Carriers: A Multicenter Histopathological Analysis

Reevaluating Antiviral Thresholds in HBV DNA-Negative Inactive HBsAg Carriers: A Multicenter Histopathological Analysis | 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 Reevaluating Antiviral Thresholds in HBV DNA-Negative Inactive HBsAg Carriers: A Multicenter Histopathological Analysis Shan Ren, Sujun Zheng, Xinyang Zhang, Junliang Fu, Rongshan Fan, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6729956/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 Jul, 2025 Read the published version in Virology Journal → Version 1 posted 9 You are reading this latest preprint version Abstract Background The definition of inactive HBsAg carriers (IHC) varies globally, particularly regarding HBV DNA thresholds. Whether HBV DNA negativity reliably predicts histological quiescence remains uncertain. Aims This study evaluated liver pathology in IHC patients to reassess antiviral therapy thresholds. Methods This multi-center, retrospective study included 231IHCs(2018–2023) stratified by HBV DNA negativity (< 20IU/mL). Liver biopsies assessed inflammation (G ≥ 2) and fibrosis (F ≥ 2); evident hepatic injury (EHI) was defined as G ≥ 2 and/or F ≥ 2. Multivariable models evaluated predictors. Results Among 231 IHC patients(median age:43 years old; 95.2% ≥30 years old), 35.9%(83/231) were HBV DNA negative. The median HBsAg and HBV DNA level were 132 IU/ml and 94 IU/ml,respectively.Notably, EHI prevalence was significantly higher in HBV DNA negative patients than positive ones(44.9% vs. 31%, P = 0.04), driven by fibrosis (F ≥ 2: 42.2% vs. 21.6%, P < 0.001), challenging the assumption that HBV DNA negativity ensures low histological risk. Male sex, HBV DNA negativity, and elevated liver stiffness measurement(LSM) independently predicted EHI (OR = 3.37, AUC = 0.747). Conclusion: HBV DNA negativity does not guarantee histological quiescence in inactive HBsAg carriers aged ≥ 30 years, with 44.9% exhibiting significant liver injury. In this population, LSM > 6.4 Kpa should prompt consideration of liver biopsy and/or initiation of antiviral therapy. Chronic hepatitis B Inactive HBsAg carriers Liver histopathology Antiviral thresholds Fibrosis Non-invasive biomarkers Figures Figure 1 Figure 2 Introduction The definition of inactive HBsAg carriers (IHC) remains controversial, particularly regarding the HBV DNA threshold for antiviral therapy.While international guidelines for the prevention and treatment of chronic hepatitis [The European Association for the Study of the Liver (EASL) 2017 version guideline [ 1 ] , and The American Association for the Study of Liver Diseases(AASLD) 2018 version guideline [ 2 ] ]maintain a threshold of < 2,000 IU/mL, the Chinese Guidelines(2022 Edition) [ 3 ] now require complete HBV DNA negativity (< 20 IU/mL) for IHC diagnosis.This revision has dual clinical significance. Firstly, it expands the population eligible for hepatitis B treatment. Recent research [ 4 ] had showed that among individuals classified under the old IHC criteria, 76% (47/61) had positive HBV DNA, with 88% (41/47) over 30 years old. Notably, the updated guidelines explicitly recommend antiviral therapy for patients aged > 30 years with detectable HBV DNA [ 3 ] , which could potentially increase treatment coverage by about 2.3 times and significantly aid in achieving WHO's goal for 2030 [ 5 ] . However,antiviral therapy remains unrecommended for patients meeting the new IHC criteria. Current evidence [ 6 – 10 ] suggests that CHB patients with low-level viremia exhibit milder hepatic injury and lower disease progression risks compared to those with high viral loads. Whether this applies to the new IHC population remains unsubstantiated by robust clinical evidence.Notably, there is a marked gap in histological data for HBV DNA negative individuals. The lack of histopathological evidence in this population has been highlighted in recent studies [ 11 ] , which underscored the necessity for further investigation into liver fibrosis and necroinflammatory activity among HBV DNA negative inactive HBsAg carriers.This multicenter retrospective study aimed to compare hepatic histology between IHC patients with HBV DNA-positive and DNA-negative. It sought to explore the correlations with clinical biomarkers to assess potential requirements for therapeutic intervention. Materials and methods Study population This multi-center, retrospective study included 231 treatment-naïve patients with IHC patients who underwent liver biopsy and pathological diagnosis at Beijing You’an Hospital and collaborating multicenter institutions between January 2018 and December 2023.Inclusion criteria were as follows: (1) Diagnosis of IHC [12] (HBsAg < 1,000IU/mL, HBeAg negative, HBV DNA<2,000IU/mL, and normal alanine aminotransferase[ALT]levels(upper limit of normal[ULN]:40U/L); (2)liver histological examination; (3) complete data, including basic information, clinical records, and laboratory tests. Exclusion criteria were as follows: (1)Other viral hepatitis(A,C,or E); (2) alcoholic liver disease, drug-induced liver injury, autoimmune liver disease, or other liver conditions; (3) progression to cirrhosis, liver cancer, or liver failure; (4) antiviral treatment within 6 months; (5) use of liver-protecting or immunomodulatory drugs within 1 month.Patients were divided into HBV DNA negative (<20 IU/mL) and HBV DNA positive (≥20 IU/mL) groups. Low normal ALT levels were defined as <30 U/L for males and <19 U/L for females, while high normal levels were 30-40 U/L for males and 19-40 U/L for females. The study protocol was permitted by the ethics committee of Beijing Youan Hospital, Capital Medical University, and the procedures were in accordance with the Helsinki declaration of 1975, as revised in 1983(The Code of Ethic Approval:[2022]159); Clinical Trials Registration Chinese Clinical Trial Registry (ChiCTR2200061541). Examination of serological markers for hepatitis B HBV markers were detected using Elecsys MODULAR ANALYTICS E170 (Roche Diagnostics GmbH, Germany):the lower limit for the quantitative detection of HBsAg was 10 IU/ml, and HBeAg>1 COI were considered positive. HBV DNA was tested using the cobas® AmpliPrep/cobas® Taqman automatic nucleic acid separation and purification and PCR analysis system (Roche Diagnostics GmbH, Germany), with a detection limit of 20 IU/ml. ALT was tested using Olympus AU5400 biochemical analyzer (Japan), and the normal value was <40U/L. Pathological Examination of Liver Tissues Ultrasonography-guided percutaneous liver biopsy was performed using a 16-gauge BARD puncture gun (Hepafix, B. Braun, Melsungen, Germany) under local anesthesia. Liver tissue samples with a minimum length of 1.5 cm and containing at least six portal tracts were considered adequate for histological evaluation. Specimens were immediately fixed with 10% neutral formalin, embedded in paraffin, and routinely stained. Histological assessment of necroinflammation and fibrosis was independently and blindly performed by at least two experienced pathologists using the METAVIR scoring system [1,12] (necroinflammation: G0–G4; fibrosis: F0–F4). Evident hepatic injury (EHI) was defined as G≥2 and/or F≥2. Liver stiffness measurement (LSM) LSM was performed using FibroScan® 502 Touch (Echosens, France) by two certified operators (each with experience of ≥500 examinations). Measurements were considered reliable only when all the following criteria were met:At least 10 valid acquisitions;Success rate >60%;Interquartile range (IQR) ≤30% of the median value. All examinations were conducted within 7 days prior to liver biopsy to ensure temporal consistency between LSM and histological assessment. Statistical Analysis All analyses were performed using SPSS 29.0 (IBM Corp.) and R 4.2.0 (glmnet package). Continuous variables were expressed as median (interquartile range) and compared using Mann-Whitney U or Kruskal-Wallis tests for non-normal data (assessed by Shapiro-Wilk test) and Student's t-test for normal distributions. Categorical variables were presented as frequencies (%) and analyzed by χ² or Fisher's exact tests. Predictors of significant liver pathology (G/F≥2) were first screened through univariable analysis (P<0.10 threshold), then entered into LASSO regression with 10-fold cross-validation (optimal λ selected by 1-standard error criterion) to construct a parsimonious model. Multicollinearity was rigorously evaluated using variance inflation factors (VIF>10 excluded). Final multivariable logistic regression results were reported as odds ratios (OR) with 95% confidence intervals. Model discrimination was assessed by receiver operating characteristic (ROC) curve analysis (AUC with DeLong 95% CI), and calibration was verified via Hosmer-Lemeshow test. All tests were two-tailed with P<0.05 considered significant, and exact P-values were reported without truncation. Results Clinical Characteristics of IHC Patients A total of 231 IHC patients were included, with men comprising 64.9% of the cohort. The median age was 43 years (IQR: 38-51), and 95.2% (220/231) were ≥30 years old. The median ALT level was 22.0 U/L (IQR: 16-29), with 65.4% (151/231) having low normal ALT levels. The median HBsAg level was 132 IU/ml (IQR: 21-401), and the median HBV DNA level was 94 IU/ml (IQR: 0-449); 35.9% (83/231) were HBV DNA negative (<20 IU/ml). Among the 148 HBV DNA positive patients, the median HBV DNA level was 246 IU/ml (IQR: 112-786). Of the 187 patients who underwent transient elastography(TE), 57.2% (107/187) had fatty liver disease(FLD) ,which means controlled attenuation parameter(CAP)>248 dB/m. The mean level of CAP was 259 ± 46 dB/m , and the median LSM was 5.55 kPa (IQR: 4.53-6.7). No significant differences were observed between HBV DNA negative and positive groups in terms of sex, age, leukocyte count, HBsAg titer, or ALT level (P > 0.05). However, LSM was significantly higher in the HBV DNA negative group (6.1 vs. 5.3, P = 0.002), as were platelet levels (187 ± 58 vs. 213 ± 57, P = 0.001). Non invasive fibrosis markers (FIB-4 and APRI) were also higher in the HBV DNA negative group (P < 0.05).The basic clinical information of the patients is shown in Table 1 . Table 1. Clinical characteristics of IHC patients by HBV DNA status Overall population (N=231) HBV DNA positive (N=148) HBV DNA negative (N=83) P value Age (years) 43 (38, 51) 42 (38, 50) 44 (37, 52) 0.481 2 ≥ 30 (n, %) 220 (95.2%) 142 (95.9%) 78 (94.0%) 0.530 3 Male (n, %) 150 (64.9%) 90 (60.8%) 60 (72.3%) 0.079 4 Serum virological indicators HBV DNA (IU/mL) 94 (0, 449) 246 (112, 786) 0 (0, 0) <0.001 2 HBsAg (IU/mL) 132 (21, 401) 134 (32, 350) 131 (2, 509) 0.65 2 Serum biochemical indicators ALT (U/L) 22 (16, 29) 22 (16, 27) 21 (16, 32) 0.46 2 ALT group (n, %) 0.34 4 Low-normal 151 (65.4%) 100 (67.6%) 51 (61.4%) High-normal 80 (34.6%) 48 (32.4%) 32 (38.6%) AST (U/L) 22.0 (19.0, 26.0) 22.0 (19.0, 25.0) 23.0 (18.0, 27.0) 0.42 2 WBC 5.54 (4.64, 6.48) 5.54 (4.80, 6.64) 5.56 (4.38, 6.22) 0.3 2 ANC 3.21 (2.57, 3.91) 3.23 (2.60, 4.09) 3.20 (2.43, 3.74) 0.24 2 PLT 204 ± 58 213 ± 57 187 ± 58 0.001 5 CAP 259 ± 46 259 ± 44 259 ± 49 0.96 5 FLD (n, %) 107 (57.2%) 68 (57.6%) 39 (56.5%) 0.88 4 LSM 5.55 (4.53, 6.70) 5.30 (4.45, 6.10) 6.10 (4.80, 7.95) 0.002 2 LSM>7 (n，%) 40 (19.4%) 15 (11.8%) 25 (31.6%) <0.001 4 APRI 0.27 (0.22, 0.36) 0.26 (0.20, 0.32) 0.29 (0.23, 0.41) 0.007 2 FIB-4 0.21 (0.16, 0.33) 0.20 (0.15, 0.31) 0.27 (0.18, 0.36) 0.03 2 1 Median (IQR); n (%); mean ± SD; 2 Wilcoxon rank sum test; 3 Fisher's exact test; 4 Pearson's chi-square test; 5 Welch two-sample t test; **EHI: evident hepatic injury; non-EHI: non-evident hepatic injury; APRI: Aspartate aminotransferase(AST) to platelet(PLT)ratio index,[AST(U/L)/ULN of AST]/PLT(10 9 /L)×100; FIB-4:fibrosis index based on 4 factors,[age(years)×AST(U/L)]/[PLT (10 9 /L)×(ALT [U/L])¹/2] Liver tissue pathology, characteristics of inflammation and fibrosis As delineated in Table 2 , the majority of IHC patients exhibited mild liver inflammation (G1: 81.8%, 189/231), whereas significant inflammation (G≥2) was observed in only 16.5% (38/231) of cases (Fig.1A) , comprising G2 (15.6%, 36/231) and G3 (0.9%, 2/231) with no G4 cases detected. In contrast, advanced fibrosis (F≥2) was more prevalent (29%, 67/231), distributed as F2 (18.6%, 43/231) and F3 (10.4%, 24/231), with mild fibrosis (F1) accounting for 56.3% (130/231). Patients with non-EHI(G<2 and F<2) constituted 64.1% (148/231) of the cohort.Notably, as shown in Figure 1A, 35.9% (83/231) met the criteria for EHI (G≥2 and/or F≥2), with a significantly higher prevalence in HBV DNA-negative patients compared to HBV DNA-positive counterparts (44.6% vs. 31.1%; P = 0.04). Fibrosis stage emerged as the primary contributor to EHI, with 29% (67/231) demonstrating F≥2. Strikingly, HBV DNA-negative patients exhibited over twice the prevalence of F≥2 fibrosis relative to HBV DNA-positive individuals (42.2%, 35/83 vs. 21.6%, 32/148; P < 0.001).Intriguingly, despite a numerical predominance of severe inflammation (G≥2) in HBV DNA-positive patients (18.2%, 27/148 vs. 13.3%, 11/83), this disparity lacked statistical significance (P = 0.32). Table 2 . liver tissue pathology of IHC patients in all patients (n=231) All patients(N=231) F0,n(%) F1,n(%) F2,n(%) F3,n(%) Total G0 3(1.3%) 0(0.0%) 1 (0.4%) 0 (0.0%) 4(1.7%) G1 30(13.0%) 115 (49.8%) 30 (13.0%) 14(6.1%) 189 (81.8%) G2 0(0.0%) 15(6.5%) 12(5.2%) 9(3.9%) 36(15.6%) G3 1(0.4%) 0(0.0%) 0(0.0%) 1(0.4%) 2(0.9%) Total 34(14.7%) 130(56.3%) 43(18.6%) 24(10.4%) 231(100.0%) *The classification of liver inflammation activity (G; 0-4) ; the stage of fibrosis (F; 0-4). Age-stratified analyses (Supplementary Table 1 and Fig.1B ) revealed divergent patterns.In younger patients ( 0.05).As shown in Fig.1B and Table 3 ,among patients ≥30 years (n=220), HBV DNA-negative status remained associated with elevated EHI prevalence (44.9%[33/78] vs. 31.0%[44/142]; P = 0.04), driven predominantly by advanced fibrosis (F≥2: 42.3%[33/78] vs. 21.1%[30/142]; P < 0.001). These findings collectively suggest that HBV DNA-negative status correlates with accelerated fibrogenesis, particularly in patients beyond 30 years of age. Table 3 . liver tissue pathology of IHC patients over the age of 30 (n=220) Patients≥30years old (n=220) EHI (G≥2 and/or F≥2) Non-EHI Total HBV DNA positive 44（31%） 98（69%） 142 HBV DNA negative 35（44.9%） 43（55.1%） 78 Total 79 141 220 *EHI:Evidenced hepatic injury (EHI) were defined asnecroinflammation grade≥2(≥G2)and/or fibrosis stage≥2(≥F2) Analysis of factors influencing liver tissue EHI in IHC patients over 30 years old In this cohort of IHC patients aged ≥30 years (n=220, 95.2% of total cohort), 31% (79/220) exhibited EHI. Univariate logistic regression identified male sex (OR 3.37, 95%CI 1.22-9.30, p=0.019), HBV DNA negativity (OR 1.94, p=0.054), PLT, elevated ALT (>40 U/L), and non-invasive fibrosis indices including LSM, APRI, and FIB-4 as potential predictors of EHI ( Table 4 ). Multivariable logistic regression analysis identified two independent predictors of EHI in this cohort. Specifically, LSM Table 4 : Logistic regression analysis of factors influencing EHI (G≥2 and/or F ≥ 2 ) in IHC patients over 30 years old Characteristic Univariable Multivariable Total (n=220) EHI (n=79) OR 1 95% CI 1 p-value Total (n=178) EHI (n=59) OR 1 95% CI 1 p-value sex female 77 19 — — 60 12 — — male 143 60 2.21 1.19, 4.08 0.012 118 47 age 220 79 1.02 0.99, 1.06 0.139 178 59 1.02 0.98, 1.07 0.263 HBsAg (log10) 220 79 1.06 0.83, 1.34 0.657 178 59 1.31 0.94, 1.82 0.108 HBV DNA_group positive 142 44 — — 115 29 — — negative 78 35 1.81 1.02, 3.21 0.041 63 30 1.94 0.89, 4.22 0.054 WBC 219 78 0.98 0.88, 1.09 0.676 178 59 1.54 0.88, 2.70 0.132 PLT 220 79 0.99 0.99, 1.00 0.023 178 59 0.99 0.99, 1.00 0.142 ANC 218 78 0.98 0.89, 1.07 0.636 178 59 0.71 0.37, 1.36 0.306 ALT 220 79 1.04 1.00, 1.07 0.030 178 59 1.02 0.94, 1.11 0.638 AST 220 79 1.03 0.99, 1.07 0.124 178 59 1.02 0.95, 1.10 0.599 ALT group low normal 145 50 — — 116 36 — — high normal 75 29 1.20 0.67, 2.13 0.540 62 23 0.91 0.24, 3.51 0.891 F LD non-FLD 79 26 — — FLD 100 34 1.05 0.56, 1.96 0.878 CAP 179 60 1.00 0.99, 1.01 0.912 178 59 0.99 0.99, 1.00 0.161 LSM 197 66 1.31 1.14, 1.51 <0.001 178 59 1.33 1.11, 1.59 0.002 APRI 220 79 12.33 2.14, 71.05 0.005 1 OR = Odds Ratio, CI = Confidence Interval Null deviance = 226; Null df = 177; Log-likelihood = -85.7; AIC = 189; BIC = 218; Deviance = 171; Residual df = 169; No. Obs. = 178 Note: FIB-4: Fibrosis-4; APRI: aspartate aminotransferase-to-platelet ratio index; LSM: liver stiffness measurement; demonstrated a dose-dependent association with EHI risk, with each 1 kPa increment corresponding to a 33% increase in adjusted odds (OR 1.33, 95%CI 1.11-1.59; p = 0.002). Additionally, male sex emerged as a significant risk factor, showing a 3.37 fold higher likelihood of EHI compared to females (95% CI 1.22-9.30).Notably, FIB-4 and APRI were excluded from the final model due to significant multicollinearity (VIF=12.908 and 10.953, respectively). To comparatively assess predictive performance, we evaluated the novel model against conventional indices (FIB-4, APRI) using ROC curve analysis. To develop a parsimonious predictive model for EHI, we performed least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation on 15 candidate clinical variables ( Supplementary Table 2 ,Fig.2A ). Three independent predictors were identified:Male sex (β = 0.732, standard error [SE] = 0.315),HBV DNA negative (β = 0.614, SE = 0.287),LSM(β = 0.253 per kPa, SE = 0.082).The final logistic regression model was formulated as:logit(P) = -3.193 + 0.732 × (Male sex) + 0.614 × (Undetectable HBV DNA) + 0.253 × (LSM).In the training cohort (n=154), the model demonstrated robust discriminative performance, with an area under the receiver operating characteristic curve (AUROC) of 0.747 (95% CI: 0.658-0.836, Fig.2B ). Internal validation(n = 66, Supplementary Table 3 ) further confirmed superior predictive accuracy (AUROC = 0.72, 95%CI 0.58-0.86, Fig.2C ).The novel model showed statistically significant improvements over established biomarkers, with absolute AUROC increases of 21.9% versus AST/ALT ratio (DeLong's test p=0.008), 25.8% versus FIB-4 (p=0.002), and 19.5% versus APRI (p=0.011) ( Fig . 2B ).As shown in Figure 2D , the model predicted that the probability of male patients over 30 years of age with HBV DNA negativity and an LSM greater than 6.4 kPa having EHI in the liver tissues reached 72.8%,greater than the percentage of female patients with positive HBV DNA and an LSM less than 6.4 kPa (6.9%), while the percentage of other patients with significant liver tissue fibrosis was 40.1%; the differences in these percentages was significant (χ 2 =25.9, P < 0.001). Discussion This study included 231 IHC individuals, adhering to the standards outlined in the Chinese Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2019 Edition). Both the HBV DNA-negative group(< 20 IU/ml) and the positive group(20-2000 IU/ml)exhibited significant risks of liver inflammation or fibrosis, with an overall incidence rate of EHI at 35.9%, and a proportion of F ≧ 2 recorded at 29%. Notably, the prevalence of significant fibrosis in the HBV DNA-negative group was markedly higher (42.2%) compared to that in the positive group (21.6%, P < 0.001). This disparity was particularly pronounced among individuals over the age of 30, indicating that age-related immune senescence mechanisms may play a critical role in the fibrotic progression observed in HBV DNA-negative patients. Prolonged interactions between the virus and host could lead to immune senescence phenotypes, such as T-cell exhaustion [ 13 ] , which diminishes immune surveillance capacity and ultimately contributes to the pathological characteristic of "low viral load-high fibrosis." The determination of staging in the natural history of chronic HBV infection is crucial for establishing antiviral treatment indications in clinical practice. Before 2022, neither domestic nor international guidelines [ 1 , 2 , 12 ] recommended antiviral therapy for IHC patients. However, it was stated that chronic HBV-infected individuals with EHI, as determined by liver biopsy, should receive antiviral intervention. This suggests that without a liver histological assessment, about 36% of eligible patients would miss out on treatment opportunities.Notably, the 2022 Chinese guidelines [ 3 ] introduced significant changes to IHC staging criteria: Patients with HBsAg < 1000 IU/mL and positive HBV DNA levels between 20-2000 IU/mL are now classified as being in a "gray zone" and are included within the scope for antiviral treatment. This revision not only encompasses patients who have not undergone pathological examination but also those already showing histological indications for therapy. It marks an important advancement in expanding treatment criteria for chronic HBV infection and promoting proactive interventions in China. Currently, antiviral treatment is not recommended for IHC individuals with negative HBV DNA levels; however, it remains unclear if this correlates with milder liver damage. Research shows that 44.6% of patients in the negative group presented with EHI—a significantly higher rate—while those scoring S ≥ 2 were more prevalent in the negative group compared to the positive group (42.2% vs 21.6%, P < 0.001).In contrast, there was no significant difference between the two groups regarding G ≥ 2 scores, recorded at 13.3% and 18.2%, respectively (P = 0.320). These findings suggest that negative HBV DNA may indicate a mild degree of liver inflammation; conversely, a higher proportion of individuals with negative HBV DNA exhibited S ≥ 2 scores. This aligns with the EASL Guidelines for the Prevention and Treatment of Chronic Hepatitis B published in 2017 [ 1 ] , which state that low levels of HBsAg and HBV DNA reflect only a certain stage of HBV infection without accurately indicating liver tissue damage extent. Therefore, relying solely on HBV DNA to determine antiviral treatment needs in IHC patients is inadequate; without assessing liver tissue status, nearly half of newly defined IHC patients may miss potential antiviral therapy opportunities. Thus, even with negative HBV DNA results alongside low HBsAg levels and normal ALT values, clinicians must remain vigilant and investigate factors contributing to fibrosis in this subset of IHC patients. Among the IHC patients in this study, those over 30 years old made up a significant 95.2%, aligning with the established high-risk age for disease progression noted in previous research [ 14 , 15 ] . In China, mother-to-child transmission is the primary mode of HBV spread [ 3 ] , which means that CHB patient ages reflect chronic HBV infection's disease course. Research [ 16 ] shows that HCC incidence among IHC patients in East Asia is about 0.2 cases per 100 person-years, while this rate has dropped by 90% in Europe and America due to differences in viral transmission and age distributions. Due to clinical limitations of liver biopsy procedures, we aimed to use non-invasive diagnostic models like LSM, APRI, and FIB-4 to evaluate liver fibrosis severity within the IHC population. Our results indicated significantly higher LSM and APRI values for individuals in the S ≥ 2 group compared to those in the S < 2 group. Combining LSM with gender and negative HBV DNA yielded an AUC of 0.75 for EHI, outperforming single indicators such as FIB-4, APRI, and AST/ALT (P 6.4 kPa and HBV DNA is negative, diagnostic sensitivity for significant fibrosis increases markedly; thus antiviral treatment should be initiated.This threshold demonstrated a positive predictive value of 72.8% within the study cohort, thereby complementing the cirrhosis warning standard (LSM ≧ 8.0 kPa) proposed by F. Cinque, J et al [ 17 ] and the recommendations set forth by the EASL [ 1 ] . This integration forms a complementary stepwise management scheme. Furthermore, it provides a practical decision-making tool for primary medical institutions that lack the capacity to perform biopsies. Current evidence supports the necessity of antiviral treatment for IHC patients [ 18 , 19 ] . This research, through liver histology, showed that regardless of the IHC criteria used-new or old-a significant cohort has unmet treatment needs.Benefit analysis shows that the 96-week HBsAg loss rate in DNA-negative patients treated with PEG-IFNα is 51.1%, significantly higher than the positive group (38.8%,P < 0.05), with a subsequent HCC incidence dropping to 0.76% [ 20 ] . This "low-virus-high-response" phenomenon may be relate to reduced viral integration [ 21 ] and remodeled the distinct intrahepatic immune microenvironment [ 22 ] . Meanwhile, in the DNA-negative state, HBV cccDNA is highly methylated, inhibiting HBx protein transcription and enhancing interferon's antiviral effects on viral replication [ 23 ] . These findings provide a biological basis for using the DNA-negative state as a screening marker to identify suitable candidates for interferon treatment. Clinical cure, the ideal endpoint of CHB treatment, significantly enhances long-term prognosis. In non-cirrhotic populations, the recurrence rate and risk of HCC after HBsAg loss are reduced to 9.7% and 0.76%, respectively [ 20 , 24 – 26 ] . Notably, IHC patients have the lowest recurrence rate at 3.3% post-clearance and show no progression to cirrhosis or HCC [ 26 ] . Additionally, HCC incidence among non-cirrhotic IHC patients drops to 0.76% [ 20 ] . These findings suggest that the PEG-IFNα-2a regimen is both feasible-achieving a clinical cure rate over 44%-and safe, with end-stage liver disease incidence below 1%. Early achievement of clinical cure can maximize patient benefits [ 25 ] , highlighting the need for timely intervention based on histological characteristics observed in liver tissue.The current cross-sectional study has inherent limitations: selection bias from preferential biopsy in high-risk patients [ 27 ] , underestimated pathological heterogeneity in this single-center cohort [ 28 ] , and unvalidated fibrosis progression due to limited follow-up. These constraints may affect generalizability, requiring validation through prospective multi-center studies. This study highlights crucial fibrosis risk assessment needs in HBV DNA-negative IHC patients,with 44.6% meeting histological treatment criteria. A stepwise strategy integrating age, sex, and LSM is recommended. This cohort demonstrates high cure rates, low recurrence, and improved outcomes, warranting multi-center RCTs to validate immunomarker-guided strategies. Declarations Ethics Statement The study protocol was permitted by the ethics committee of Beijing Youan Hospital, Capital Medical University, and the procedures were in accordance with the Helsinki declaration of 1975, as revised in 1983(The Code of Ethic Approval:[2022]159) Ethics Committee approval was obtained from the Institutional Ethics Committee of Capital Medical University Beijing Youan Hospital to the commencement of the study. Clinical Trials Registration Chinese Clinical Trial Registry (ChiCTR2200061541). Conflict of Interest declaration: The authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript. Author Contribution Ren Shan and Zheng Sujun were instrumental in the conception of the study. Zhang Xinyang was responsible for collecting the pathological data, while Ma Lina and Zheng Yanhong gathered the clinical data. Fan Rongshan, Ruan Qingfa, Huang Wenqi, and other physicians from Shenzhen Third People's Hospital, along with Gao Haibing, Xue Xiulan, and Yang Fang, contributed clinical and pathological data of IHC patients from their respective hospitals as part of the 'STARHB' real-world study. Ren Shan and Zhang Xinyang played a significant role in the analysis and manuscript preparation. Ren Shan, Zheng Sujun, and Chen Xinyue performed the data analyses and wrote the manuscript. Chen Xinyue and Ren Shan also contributed to the analysis with insightful and constructive discussions. Funding We are grateful to all the subjects who participated in this study. This work was supported by the National Key Research and Development Program of Ministry of Science and Technology(2023YFC2308100), Capital Clinical Diagnostic Techniques and Translational Application Projects (Z211100002921059), The STARHB Project (The STUDY ON TREATMENT FOR INACTIVE CARRIERS OF HEPATITIS B),High-level public health technical talents construction project of Beijing Municipal Health Commission (Academic Leader -02-14),Capital’s Funds for Health Improvement and Research(2024-2-2184),Beijing Natural Science Foundation (No. 7222093).The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Data Availability The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. References European Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol 2017;67(2):370-398. DOI:10.1016/j.jhep.2017.03.021. Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018;67(4):1560-1599. DOI:10.1002/hep.29800. Chinese Society of Hepatology, Chinese Society of Infectious Diseases. Guidelines for the prevention and treatment of chronic hepatitis B (2022 version). Chin J Clin Infect Dis 2022;15(6):401-427. DOI:10.3760/cma.j.issn.1674-2397.2022.06.001. Ren S, Wang W, Lu J, et al. Effect of the change in antiviral therapy indication on identifying significant liver injury among chronic hepatitis B virus infections in the grey zone. Front Immunol 2022;13:1035923. DOI:10.3389/fimmu.2022.1035923. Liu J, Liang W, Jing W, et al. Countdown to 2030: Eliminating hepatitis B disease, China. Bull World Health Organ 2019;97(3):230-238. DOI:10.2471/BLT.18.219469. Yuen MF, Tanaka Y, Fong DYT, et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J Hepatol 2009;50(1):80-88. DOI:10.1016/j.jhep.2008.07.023. Raffetti E, Fattovich G, Donato F. Incidence of hepatocellular carcinoma in untreated subjects with chronic hepatitis B: A systematic review and meta-analysis. Liver Int 2016;36(9):1239-1251. DOI:10.1111/liv.13142. Eilard A, Ringlander J, Andersson ME, et al. Long-term outcome of chronic hepatitis B-histological score and viral genotype are important predictors of hepatocellular carcinoma. J Viral Hepat 2025;32(3):e70008. DOI:10.1111/jvh.70008. Kim GA, Choi SW, Han S, et al. Non-linear association between liver fibrosis scores and viral load in patients with chronic hepatitis B. Clin Mol Hepatol 2024;30(4):793-806. DOI:10.3350/cmh.2024.0252. Chen CJ, Yang HI, Iloeje UH, et al. Hepatitis B virus DNA levels and outcomes in chronic hepatitis B. Hepatology 2009;49(5 Suppl):S72-S84. DOI:10.1002/hep.22884. Loglio A, Viganò M. Stopping nucleos(t)ide analogues treatment in non-cirrhotic HBeAg-negative patients: Yes, we can! Dig Liver Dis 2023;55(9):1221-1222. DOI:10.1016/j.dld.2023.06.030. Chinese Society of Infectious Diseases, Chinese Society of Hepatology. Guidelines for the prevention and treatment of chronic hepatitis B (2019 version). Chin J Infect Dis 2019;37(12):711-736. Rossi M, Vecchi A, Guerrieri F, Levrero M, Boni C. Characterization of transcriptional and functional CD8 T cell heterogeneity to design individualized correction strategies for chronic HBV infection. Dig Liver Dis 2025;57(1):S68. World Health Organization. WHO-HIV-2016.06-chi. Geneva: WHO, 2016. Jiang C, Liu J, Li R, et al. Clinicopathologic features of liver inflammation and fibrosis in 310 patients with chronic hepatitis B. J Cent South Univ (Med Sci) 2023;48(5):698-706. Ni H, Ji H, Li K, et al. Analysis of liver pathologic inflammatory fibrosis and influencing factors in 721 patients with ALT-normal chronic hepatitis B. Chin J Hepatol 2022;30(7):746-751. Cinque F, Milic J, Renzetti S. The effect of metabolic dysfunction-associated steatotic liver disease on liver fibrosis progression and regression in virus-related liver disease: a multicenter longitudinal study. Dig Liver Dis 2024;56(1):S47-S48. Yardeni D, Chang KM, Ghany MG. Current Best Practice in Hepatitis B Management and Understanding Long-term Prospects for Cure. Gastroenterology 2023;164(1):42-60.e6. DOI:10.1053/j.gastro.2022.10.008. Wu WJ, Lin CL, Liu CJ, et al. Lifetime risk of liver-related outcomes and determinants in male inactive carriers of chronic hepatitis B. J Med Virol 2023;95(10):e29138. DOI:10.1002/jmv.29138. Song A, Wang X, Lu J, et al. Durability of hepatitis B surface antigen seroclearance and subsequent risk for hepatocellular carcinoma: a meta-analysis. J Viral Hepat 2021;28(4):601-612. DOI:10.1111/jvh.13471. Midorikawa Y, Tatsuno K, Moriyama M. Genome-wide analysis of hepatitis B virus integration in hepatocellular carcinoma: Insights from next generation sequencing. Hepatobiliary Surg Nutr 2021;10(4):548-552. DOI:10.21037/hbsn-21-228. Reina-Campos M, Monell A, Ferry A, et al. Tissue-resident memory CD8 T cell diversity is spatiotemporally imprinted. Nature 2025;639:483-492. DOI:10.1038/s41586-024-08466-x. Mu D, Yuan FC, Chen Y, et al. Baseline value of intrahepatic HBV DNA over cccDNA predicts patient’s response to interferon therapy. Sci Rep 2017;7:5937. DOI:10.1038/s41598-017-05242-y. Chon YE, Kim DJ, Kim SG, et al. An observational, multicenter, cohort study evaluating the antiviral efficacy and safety in Korean patients with chronic hepatitis B receiving pegylated interferon-alpha 2a (pegasys): TRACES study. Medicine (Baltimore) 2016;95(14):e3026. DOI:10.1097/MD.0000000000003026. Sun J, Ding H, Chen G, et al. Sustained serological and complete responses in HBeAg-positive patients treated with peginterferon alfa-2b: a 6-year long-term follow-up of a multicenter, randomized, controlled trial in China. BMC Gastroenterol 2019;19(1):65. DOI:10.1186/s12876-019-0981-5. Wu Y, Liu Y, Lu J, et al. Durability of interferon-induced hepatitis B surface antigen seroclearance. Clin Gastroenterol Hepatol 2020;18(2):514-516.e2. DOI:10.1016/j.cgh.2019.04.020. Fusai GK, Tamburrino D, Partelli S, et al. Portal vein resection during pancreaticoduodenectomy for pancreatic neuroendocrine tumors: an international multicenter comparative study. Surgery 2021;169(5):1093-1101. DOI:10.1016/j.surg.2020.11.015. Liu JK, Kam LY, Huang DQ. Racial and ethnic disparities in characteristics and care patterns of chronic hepatitis B patients in the United States. Clin Gastroenterol Hepatol 2023;21(10):2606-2615.e7. DOI:10.1016/j.cgh.2023.01.035. Additional Declarations No competing interests reported. Supplementary Files SupplementaryTable13.docx Cite Share Download PDF Status: Published Journal Publication published 10 Jul, 2025 Read the published version in Virology Journal → Version 1 posted Editorial decision: Revision requested 13 Jun, 2025 Reviews received at journal 10 Jun, 2025 Reviews received at journal 07 Jun, 2025 Reviewers agreed at journal 03 Jun, 2025 Reviewers agreed at journal 02 Jun, 2025 Reviewers invited by journal 29 May, 2025 Editor assigned by journal 26 May, 2025 Submission checks completed at journal 26 May, 2025 First submitted to journal 23 May, 2025 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. 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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-6729956","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":464661405,"identity":"930e4882-e29f-484b-88f8-6048e8669e9b","order_by":0,"name":"Shan Ren","email":"","orcid":"","institution":"Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shan","middleName":"","lastName":"Ren","suffix":""},{"id":464661406,"identity":"48061fdf-4056-40fe-821e-fbad8ec70bb5","order_by":1,"name":"Sujun Zheng","email":"","orcid":"","institution":"Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Sujun","middleName":"","lastName":"Zheng","suffix":""},{"id":464661407,"identity":"0a50554a-51b5-4b36-a2d9-f27e18699c8d","order_by":2,"name":"Xinyang Zhang","email":"","orcid":"","institution":"Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xinyang","middleName":"","lastName":"Zhang","suffix":""},{"id":464661408,"identity":"feedd615-8817-4115-805d-e71f84d169ff","order_by":3,"name":"Junliang Fu","email":"","orcid":"","institution":"Fifth Medical Center of Chinese PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Junliang","middleName":"","lastName":"Fu","suffix":""},{"id":464661409,"identity":"d225ea29-fbd8-4c91-981a-9ba1179dbf86","order_by":4,"name":"Rongshan Fan","email":"","orcid":"","institution":"Shenzhen Hospital of Integrated Traditional Chinese and Western 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University","correspondingAuthor":false,"prefix":"","firstName":"Haibing","middleName":"","lastName":"Gao","suffix":""},{"id":464661413,"identity":"bb47f7a7-f79d-43cb-b197-6d5c389acf76","order_by":8,"name":"Xiulan Xue","email":"","orcid":"","institution":"The First Affiliated Hospital of Xiamen University","correspondingAuthor":false,"prefix":"","firstName":"Xiulan","middleName":"","lastName":"Xue","suffix":""},{"id":464661414,"identity":"2f07ec3b-b843-4c8b-9b75-41d5ed802d39","order_by":9,"name":"Fang Yang","email":"","orcid":"","institution":"Shenyang Sixth People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Fang","middleName":"","lastName":"Yang","suffix":""},{"id":464661415,"identity":"7774e393-17c1-47b0-8163-d35599856cf1","order_by":10,"name":"Yao Xie","email":"","orcid":"","institution":"Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yao","middleName":"","lastName":"Xie","suffix":""},{"id":464661416,"identity":"8a1e47e6-006f-449b-8ee2-3119c088107a","order_by":11,"name":"Minghui Li","email":"","orcid":"","institution":"Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Minghui","middleName":"","lastName":"Li","suffix":""},{"id":464661417,"identity":"e17dd5fc-0c3c-4a31-8076-3496a30e8c4b","order_by":12,"name":"Xinyue Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAv0lEQVRIiWNgGAWjYDACCTDJzMDA3tj48ANpWngONxtLkKZFIr1NgIcYHfyzm4895m2zluOf+bANqN9OTreBkCV3jqUbzmxLN5a4ndj2oIAh2djsAAEtBhI5ZhIf2w4nbpBObDeQYDiQuI2wlvxvEokgLZIH2yR4iNOSwwaxRYKRSC0SN9LMJGecA/rlTCIwkA2I8Av/jORn0jxlwBBrP/7w4YcKOzmCWsCAkQ3uTmKUg8EfolWOglEwCkbBSAQAjqM/RLeIv4AAAAAASUVORK5CYII=","orcid":"","institution":"Capital Medical University","correspondingAuthor":true,"prefix":"","firstName":"Xinyue","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-05-23 06:38:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6729956/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6729956/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12985-025-02853-0","type":"published","date":"2025-07-10T15:56:52+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":83814988,"identity":"c7c91bba-5c33-41f8-84a7-214e13187a54","added_by":"auto","created_at":"2025-06-03 07:35:09","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1427308,"visible":true,"origin":"","legend":"\u003cp\u003eOverall liver tissue pathology of IHC patients according to the age(above 30 years old or not) and HBV DNA grouping: A. all patients according to the HBV DNA group; B. all patients grouped by age(above 30 years old or not) and HBV DNA positivity.\u003c/p\u003e\n\u003cp\u003eNote: G: inflammation stage; F: fibrosis stage; EHI (G≥2 and/or F≥2), *: P\u0026lt;0.05; ***: P\u0026lt;0.001;ns:non significantly.\u003c/p\u003e","description":"","filename":"fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-6729956/v1/3952debbfe9aec9290a91cd5.png"},{"id":83815996,"identity":"3c4b6bb1-dbc4-4883-8bfd-1688ef58d6a6","added_by":"auto","created_at":"2025-06-03 07:43:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":338732,"visible":true,"origin":"","legend":"\u003cp\u003e(A)Ranking of clinical variables for predicting perioperative complication bythe Lasso regression:sex, HBV.DNA_group and LSM; (B)Multiple non-invasive models for diagnosing histologically \u0026nbsp;defined EHI using ROC curves(AUC=0.747);(C)ROC curves for the model in the training and internal test cohorts,the training cohort (blue curve) achieved an AUC of 0.747 (95% CI: 0.658–0.831), while the internal test cohort (red curve) yielded an AUC of 0.720 (95% CI: 0.579–0.861). (D)Predicted probabilities of EHI in IHC patients over 30 years old:the model predicted distinct probabilities of liver fibrosis across subgroups: male patients aged \u0026gt;30 years with undetected HBV DNA and LSM ≥6.4 kPa exhibited the highest probability (72.8%), significantly surpassing that of female patients with detectable HBV DNA and LSM \u0026lt;6.4 kPa (6.9%). The probability for other patient subgroups was 40.1%. These differences were statistically significant (χ² = 25.9, P \u0026lt; 0.001). Note: ROC:Receiver operating characteristic;AUC:area under the receiver operating characteristic curve;FIB-4: Fibrosis-4; APRI: aspartate aminotransferase-to-platelet ratio index; LSM: liver stiffness measurement\u003c/p\u003e","description":"","filename":"fig.2.png","url":"https://assets-eu.researchsquare.com/files/rs-6729956/v1/29db105aca6768adfa67069a.png"},{"id":86699237,"identity":"24aba5b9-74fd-4520-aba2-d4e892db74f5","added_by":"auto","created_at":"2025-07-14 16:03:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2667540,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6729956/v1/d96e9927-e988-41bb-ae21-e781e8dbf3b0.pdf"},{"id":83814989,"identity":"39176d27-6693-4f78-b4a2-5a097adc78f6","added_by":"auto","created_at":"2025-06-03 07:35:09","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":38680,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable13.docx","url":"https://assets-eu.researchsquare.com/files/rs-6729956/v1/93ded0e111706f56dbfdfdc8.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Reevaluating Antiviral Thresholds in HBV DNA-Negative Inactive HBsAg Carriers: A Multicenter Histopathological Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe definition of inactive HBsAg carriers (IHC) remains controversial, particularly regarding the HBV DNA threshold for antiviral therapy.While international guidelines for the prevention and treatment of chronic hepatitis [The European Association for the Study of the Liver (EASL) 2017 version guideline\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e, and The American Association for the Study of Liver Diseases(AASLD) 2018 version guideline\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e]maintain a threshold of \u0026lt;\u0026thinsp;2,000 IU/mL, the Chinese Guidelines(2022 Edition)\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e now require complete HBV DNA negativity (\u0026lt;\u0026thinsp;20 IU/mL) for IHC diagnosis.This revision has dual clinical significance. Firstly, it expands the population eligible for hepatitis B treatment. Recent research\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e had showed that among individuals classified under the old IHC criteria, 76% (47/61) had positive HBV DNA, with 88% (41/47) over 30 years old. Notably, the updated guidelines explicitly recommend antiviral therapy for patients aged\u0026thinsp;\u0026gt;\u0026thinsp;30 years with detectable HBV DNA\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e, which could potentially increase treatment coverage by about 2.3 times and significantly aid in achieving WHO's goal for 2030\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. However,antiviral therapy remains unrecommended for patients meeting the new IHC criteria.\u003c/p\u003e \u003cp\u003eCurrent evidence\u003csup\u003e[\u003cspan additionalcitationids=\"CR7 CR8 CR9\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e suggests that CHB patients with low-level viremia exhibit milder hepatic injury and lower disease progression risks compared to those with high viral loads. Whether this applies to the new IHC population remains unsubstantiated by robust clinical evidence.Notably, there is a marked gap in histological data for HBV DNA negative individuals. The lack of histopathological evidence in this population has been highlighted in recent studies\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e, which underscored the necessity for further investigation into liver fibrosis and necroinflammatory activity among HBV DNA negative inactive HBsAg carriers.This multicenter retrospective study aimed to compare hepatic histology between IHC patients with HBV DNA-positive and DNA-negative. It sought to explore the correlations with clinical biomarkers to assess potential requirements for therapeutic intervention.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis multi-center, retrospective study included 231 treatment-na\u0026iuml;ve patients with IHC patients who underwent liver biopsy and pathological diagnosis at Beijing You\u0026rsquo;an Hospital and collaborating multicenter institutions between January 2018 and December 2023.Inclusion criteria\u0026nbsp;were as follows: (1) Diagnosis of IHC\u003csup\u003e[12]\u003c/sup\u003e (HBsAg \u0026lt; 1,000IU/mL, HBeAg negative, HBV DNA\u0026lt;2,000IU/mL, and\u0026nbsp;normal alanine aminotransferase[ALT]levels(upper limit of normal[ULN]:40U/L);\u0026nbsp;(2)liver histological examination; (3) complete data, including basic information, clinical records, and laboratory tests. Exclusion\u0026nbsp;criteria\u0026nbsp;were as follows:\u0026nbsp;(1)Other viral hepatitis(A,C,or\u0026nbsp;E); (2) alcoholic liver disease, drug-induced liver injury, autoimmune liver disease, or other liver conditions; (3) progression to cirrhosis, liver cancer, or liver failure; (4) antiviral treatment within 6 months; (5) use of liver-protecting or immunomodulatory drugs within 1 month.Patients were divided into HBV DNA negative (\u0026lt;20 IU/mL) and HBV DNA positive (\u0026ge;20 IU/mL) groups. Low normal ALT levels were defined as \u0026lt;30 U/L for males and \u0026lt;19 U/L for females, while high normal levels were 30-40 U/L for males and 19-40 U/L for females.\u003c/p\u003e\n\u003cp\u003eThe study protocol was permitted by the ethics committee of Beijing Youan Hospital, Capital Medical University, and the procedures were in accordance with the Helsinki declaration of 1975, as revised in 1983(The Code of Ethic Approval:[2022]159); Clinical Trials Registration Chinese Clinical Trial Registry (ChiCTR2200061541).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExamination of serological markers for hepatitis B\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHBV markers were detected using Elecsys MODULAR ANALYTICS E170 (Roche Diagnostics GmbH, Germany):the lower limit for the quantitative detection of HBsAg was \u0026lt;0.05 IU/ml, anti-HBs \u0026gt;10 IU/ml, and HBeAg\u0026gt;1 COI were considered positive. HBV DNA was tested using the cobas\u0026reg; AmpliPrep/cobas\u0026reg; Taqman automatic nucleic acid separation and purification and PCR analysis system (Roche Diagnostics GmbH, Germany), with a detection limit of 20 IU/ml. ALT was tested using Olympus AU5400 biochemical analyzer (Japan), and the normal value was \u0026lt;40U/L.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePathological Examination of Liver Tissues\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUltrasonography-guided percutaneous liver biopsy was performed using a 16-gauge BARD puncture gun (Hepafix, B. Braun, Melsungen, Germany) under local anesthesia. Liver tissue samples with a minimum length of 1.5 cm and containing at least six portal tracts were considered adequate for histological evaluation. Specimens were immediately fixed with 10% neutral formalin, embedded in paraffin, and routinely stained. Histological assessment of necroinflammation and fibrosis was independently and blindly performed by at least two experienced pathologists using the METAVIR scoring system\u003csup\u003e[1,12]\u003c/sup\u003e (necroinflammation: G0\u0026ndash;G4; fibrosis: F0\u0026ndash;F4). Evident hepatic injury (EHI) was defined as G\u0026ge;2 and/or F\u0026ge;2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLiver stiffness measurement (LSM)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLSM was performed using FibroScan\u0026reg; 502 Touch (Echosens, France) by two certified operators (each with experience of \u0026ge;500 examinations). Measurements were considered reliable only when all the following criteria were met:At least 10 valid acquisitions;Success rate \u0026gt;60%;Interquartile range (IQR) \u0026le;30% of the median value.\u003c/p\u003e\n\u003cp\u003eAll examinations were conducted within 7 days prior to liver biopsy to ensure temporal consistency between LSM and histological assessment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll analyses were performed using SPSS 29.0 (IBM Corp.) and R 4.2.0 (glmnet package). Continuous variables were expressed as median (interquartile range) and compared using Mann-Whitney U or Kruskal-Wallis tests for non-normal data (assessed by Shapiro-Wilk test) and Student\u0026apos;s t-test for normal distributions. Categorical variables were presented as frequencies (%) and analyzed by \u0026chi;\u0026sup2; or Fisher\u0026apos;s exact tests. Predictors of significant liver pathology (G/F\u0026ge;2) were first screened through univariable analysis (P\u0026lt;0.10 threshold), then entered into LASSO regression with 10-fold cross-validation (optimal \u0026lambda; selected by 1-standard error criterion) to construct a parsimonious model. Multicollinearity was rigorously evaluated using variance inflation factors (VIF\u0026gt;10 excluded). Final multivariable logistic regression results were reported as odds ratios (OR) with 95% confidence intervals. Model discrimination was assessed by receiver operating characteristic (ROC) curve analysis (AUC with DeLong 95% CI), and calibration was verified via Hosmer-Lemeshow test. All tests were two-tailed with P\u0026lt;0.05 considered significant, and exact P-values were reported without truncation.\u003c/p\u003e"},{"header":"Results","content":"\u003col\u003e\n \u003cli\u003e\u003cstrong\u003eClinical Characteristics of IHC Patients\u003c/strong\u003e\u003cbr\u003eA total of 231 IHC patients were included, with men comprising 64.9% of the cohort. The median age was 43 years (IQR: 38-51), and 95.2% (220/231) were \u0026ge;30 years old. The median ALT level was 22.0 U/L (IQR: 16-29), with 65.4% (151/231) having low normal ALT levels. The median HBsAg level was 132 IU/ml (IQR: 21-401), and the median HBV DNA level was 94 IU/ml (IQR: 0-449); 35.9% (83/231) were HBV DNA negative (\u0026lt;20 IU/ml). Among the 148 HBV DNA positive patients, the median HBV DNA level was 246 IU/ml (IQR: 112-786). Of the 187 patients who underwent transient elastography(TE), 57.2% (107/187) had fatty liver disease(FLD) ,which means controlled attenuation parameter(CAP)\u0026gt;248 dB/m. The mean level of CAP was 259 \u0026plusmn; 46 dB/m , and the median LSM was 5.55 kPa (IQR: 4.53-6.7). No significant differences were observed between HBV DNA negative and positive groups in terms of sex, age, leukocyte count, HBsAg titer, or ALT level (P \u0026gt; 0.05). However, LSM was significantly higher in the HBV DNA negative group (6.1 vs. 5.3, P = 0.002), as were platelet levels (187 \u0026plusmn; 58 vs. 213 \u0026plusmn; 57, P = 0.001). Non invasive fibrosis markers (FIB-4 and APRI) were also higher in the HBV DNA negative group (P \u0026lt; 0.05).The basic clinical information of the patients is shown in \u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1. Clinical characteristics of IHC patients by HBV DNA status\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"120%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;Overall population\u003c/p\u003e\n \u003cp\u003e(N=231)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026nbsp;HBV DNA positive\u003c/p\u003e\n \u003cp\u003e(N=148)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e\u0026nbsp;HBV DNA negative\u003c/p\u003e\n \u003cp\u003e(N=83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e\u0026nbsp;P value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;Age (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e43 (38, 51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e42 (38, 50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e44 (37, 52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.481\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026ge;\u0026nbsp;30 (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e220 (95.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e142 (95.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e78 (94.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.530\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;Male (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e150 (64.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e90 (60.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e60 (72.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.079\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;Serum virological indicators\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;HBV DNA (IU/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e94 (0, 449)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e246 (112, 786)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0 (0, 0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;HBsAg (IU/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e132 (21, 401)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e134 (32, 350)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e131 (2, 509)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.65\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;Serum biochemical indicators\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;ALT (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e22 (16, 29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e22 (16, 27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e21 (16, 32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.46\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;ALT group (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.34\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;Low-normal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e151 (65.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e100 (67.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e51 (61.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;High-normal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e80 (34.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e48 (32.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e32 (38.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003eAST (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e22.0 (19.0, 26.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e22.0 (19.0, 25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e23.0 (18.0, 27.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.42\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;WBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e5.54 (4.64, 6.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e5.54 (4.80, 6.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e5.56 (4.38, 6.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.3\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;ANC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e3.21 (2.57, 3.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e3.23 (2.60, 4.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e3.20 (2.43, 3.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.24\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;PLT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e204 \u0026plusmn; 58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e213 \u0026plusmn; 57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e187 \u0026plusmn; 58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.001\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;CAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e259 \u0026plusmn; 46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e259 \u0026plusmn; 44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e259 \u0026plusmn; 49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.96\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;FLD (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e107 (57.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e68 (57.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e39 (56.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.88\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;LSM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e5.55 (4.53, 6.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e5.30 (4.45, 6.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e6.10 (4.80, 7.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.002\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003eLSM\u0026gt;7 (n，%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e40 (19.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e15 (11.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e25 (31.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;APRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e0.27 (0.22, 0.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e0.26 (0.20, 0.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.29 (0.23, 0.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.007\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003eFIB-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e0.21 (0.16, 0.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e0.20 (0.15, 0.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.27 (0.18, 0.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.03\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003csup\u003e1\u003c/sup\u003e Median (IQR); n (%); mean \u0026plusmn; SD; \u003csup\u003e2\u003c/sup\u003e Wilcoxon rank sum test; \u003csup\u003e3\u003c/sup\u003e Fisher\u0026apos;s exact test; \u003csup\u003e4\u003c/sup\u003e Pearson\u0026apos;s chi-square test; \u003csup\u003e5\u003c/sup\u003e Welch two-sample t test; **EHI: evident hepatic injury; non-EHI: non-evident hepatic injury; APRI: Aspartate aminotransferase(AST) to platelet(PLT)ratio index,[AST(U/L)/ULN of AST]/PLT(10\u003csup\u003e9\u003c/sup\u003e/L)\u0026times;100; FIB-4:fibrosis index based on 4 factors,[age(years)\u0026times;AST(U/L)]/[PLT (10\u003csup\u003e9\u003c/sup\u003e/L)\u0026times;(ALT [U/L])\u0026sup1;/2]\u003c/p\u003e\n\u003col start=\"2\"\u003e\n \u003cli\u003e\u003cstrong\u003eLiver tissue pathology, characteristics of inflammation and fibrosis\u0026nbsp;\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eAs delineated in Table 2\u003c/strong\u003e, the majority of IHC patients exhibited mild liver inflammation (G1: 81.8%, 189/231), whereas significant inflammation (G\u0026ge;2) was observed in only 16.5% (38/231) of cases\u003cstrong\u003e(Fig.1A)\u003c/strong\u003e, comprising G2 (15.6%, 36/231) and G3 (0.9%, 2/231) with no G4 cases detected. In contrast, advanced fibrosis (F\u0026ge;2) was more prevalent (29%, 67/231), distributed as F2 (18.6%, 43/231) and F3 (10.4%, 24/231), with mild fibrosis (F1) accounting for 56.3% (130/231). Patients\u0026nbsp;with\u0026nbsp;non-EHI(G\u0026lt;2 and F\u0026lt;2) constituted 64.1% (148/231) of the cohort.Notably,\u0026nbsp;as shown in Figure 1A, 35.9% (83/231) met the criteria for EHI (G\u0026ge;2 and/or F\u0026ge;2), with a significantly higher prevalence in HBV DNA-negative patients compared to HBV DNA-positive counterparts (44.6% vs. 31.1%; P = 0.04). Fibrosis stage emerged as the primary contributor to EHI, with 29% (67/231) demonstrating F\u0026ge;2. Strikingly, HBV DNA-negative patients exhibited over twice the prevalence of F\u0026ge;2 fibrosis relative to HBV DNA-positive individuals (42.2%, 35/83 vs. 21.6%, 32/148; P \u0026lt; 0.001).Intriguingly, despite a numerical predominance of severe inflammation (G\u0026ge;2) in HBV DNA-positive patients (18.2%, 27/148 vs. 13.3%, 11/83), this disparity lacked statistical significance (P = 0.32).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;2\u003c/strong\u003e\u003cstrong\u003e. liver tissue pathology of IHC patients\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ein all patients (n=231)\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"107%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003eAll patients(N=231)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;F0,n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003eF1,n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;F2,n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003eF3,n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;Total\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003eG0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e3(1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e0(0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e1 (0.4%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e4(1.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003eG1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e30(13.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e115 (49.8%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e30 (13.0%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e14(6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e189 (81.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003eG2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e0(0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e15(6.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e12(5.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e9(3.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e36(15.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003eG3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e1(0.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e0(0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e0(0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e1(0.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e2(0.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e34(14.7%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e130(56.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e43(18.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e24(10.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88px;\"\u003e\n \u003cp\u003e231(100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;*The classification of liver inflammation activity (G; 0-4) ; the stage of fibrosis (F; 0-4).\u003c/p\u003e\n\u003cp\u003eAge-stratified analyses (Supplementary Table 1 and\u003cstrong\u003e\u0026nbsp;Fig.1B\u003c/strong\u003e) revealed divergent patterns.In younger patients (\u0026lt;30 years, n=11), no significant inter-group differences in G and F stages or EHI were observed (P \u0026gt; 0.05).As shown in \u003cstrong\u003eFig.1B and Table 3\u003c/strong\u003e,among patients \u0026ge;30 years (n=220), HBV DNA-negative status remained associated with elevated EHI prevalence (44.9%[33/78] vs. 31.0%[44/142]; P = 0.04), driven predominantly by advanced fibrosis (F\u0026ge;2: 42.3%[33/78] vs. 21.1%[30/142]; P \u0026lt; 0.001). These findings collectively suggest that HBV DNA-negative status correlates with accelerated fibrogenesis, particularly in patients beyond 30 years of age.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;3\u003c/strong\u003e\u003cstrong\u003e. liver tissue pathology of IHC patients over the age of 30 (n=220)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"106%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003ePatients\u0026ge;30years old\u003c/p\u003e\n \u003cp\u003e(n=220)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eEHI (G\u0026ge;2 and/or\u0026nbsp;F\u0026ge;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003eNon-EHI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eHBV DNA positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003e44（31%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e98（69%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e142\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eHBV DNA negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003e35（44.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e43（55.1%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 139px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e141\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e220\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*EHI:Evidenced hepatic injury (EHI) were defined asnecroinflammation grade\u0026ge;2(\u0026ge;G2)and/or fibrosis stage\u0026ge;2(\u0026ge;F2)\u003c/p\u003e\n\u003col start=\"3\"\u003e\n \u003cli\u003e\u003cstrong\u003eAnalysis of factors influencing liver tissue\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eEHI\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;in IHC patients over 30 years old\u0026nbsp;\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eIn this cohort of IHC patients aged \u0026ge;30 years (n=220, 95.2% of total cohort), 31% (79/220) exhibited EHI. Univariate logistic regression identified male sex (OR 3.37, 95%CI 1.22-9.30, p=0.019), HBV DNA negativity (OR 1.94, p=0.054), PLT, elevated ALT (\u0026gt;40 U/L), and non-invasive fibrosis indices including LSM, APRI, and FIB-4 as potential predictors of EHI (\u003cstrong\u003eTable 4\u003c/strong\u003e). Multivariable logistic regression analysis identified two independent predictors of EHI in this cohort. Specifically, LSM\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003cstrong\u003e: Logistic regression analysis of factors influencing EHI (G\u0026ge;2 and/or\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eF\u003c/strong\u003e\u003cstrong\u003e\u0026ge;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e) in IHC patients over 30 years old\u0026nbsp;\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"718\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 296px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 325px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=220)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEHI\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=79)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 45px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=178)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEHI\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=59)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003esex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e2.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e1.19, 4.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e1.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.99, 1.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.139\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.98, 1.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.263\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHBsAg\u003c/strong\u003e\u003cstrong\u003e(log10)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e1.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.83, 1.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.657\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.94, 1.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.108\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHBV DNA_group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003epositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e142\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003enegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e1.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e1.02, 3.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.89, 4.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWBC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e219\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.88, 1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.676\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.88, 2.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.132\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePLT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.99, 1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.99, 1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.142\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eANC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e218\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.89, 1.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.636\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.37, 1.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.306\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e1.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e1.00, 1.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.030\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.94, 1.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.638\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAST\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.99, 1.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.95, 1.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.599\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALT group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003elow normal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e145\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003ehigh normal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e1.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.67, 2.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.540\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.24, 3.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.891\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF\u003c/strong\u003e\u003cstrong\u003eLD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003enon-FLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003eFLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.56, 1.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.878\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCAP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e179\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.99, 1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.912\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.99, 1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.161\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLSM\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e197\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e1.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e1.14, 1.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e1.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e1.11, 1.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAPRI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e12.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e2.14, 71.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003eOR = Odds Ratio, CI = Confidence Interval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNull deviance = 226; Null df = 177; Log-likelihood = -85.7; AIC = 189; BIC = 218; Deviance = 171; Residual df = 169; No. Obs. = 178\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNote: FIB-4: Fibrosis-4; APRI: aspartate aminotransferase-to-platelet ratio index; LSM: liver stiffness measurement;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003edemonstrated a dose-dependent association with EHI risk, with each 1 kPa increment corresponding to a 33% increase in adjusted odds (OR 1.33, 95%CI 1.11-1.59; p = 0.002). Additionally, male sex emerged as a significant risk factor, showing a 3.37 fold higher likelihood of EHI compared to females (95% CI 1.22-9.30).Notably, FIB-4 and APRI were excluded from the final model due to significant multicollinearity (VIF=12.908 and 10.953, respectively). To comparatively assess predictive performance, we evaluated the novel model against conventional indices (FIB-4, APRI) using ROC curve analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo develop a parsimonious predictive model for EHI, we performed least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation on 15 candidate clinical variables (\u003cstrong\u003eSupplementary Table 2\u003c/strong\u003e\u003cstrong\u003e,Fig.2A\u003c/strong\u003e). Three independent predictors were identified:Male sex (\u0026beta; = 0.732, standard error [SE] = 0.315),HBV DNA negative (\u0026beta; = 0.614, SE = 0.287),LSM(\u0026beta; = 0.253 per kPa, SE = 0.082).The final logistic regression model was formulated as:logit(P) = -3.193 + 0.732 \u0026times; (Male sex) + 0.614 \u0026times; (Undetectable HBV DNA) + 0.253 \u0026times; (LSM).In the training cohort (n=154), the model demonstrated robust discriminative performance, with an area under the receiver operating characteristic curve (AUROC) of 0.747 (95% CI: 0.658-0.836,\u003cstrong\u003eFig.2B\u003c/strong\u003e). Internal validation(n = 66,\u003cstrong\u003e\u0026nbsp;Supplementary Table 3\u003c/strong\u003e) further confirmed superior predictive accuracy (AUROC = 0.72, 95%CI 0.58-0.86,\u003cstrong\u003eFig.2C\u003c/strong\u003e).The novel model showed statistically significant improvements over established biomarkers, with absolute AUROC increases of 21.9% versus AST/ALT ratio (DeLong\u0026apos;s test p=0.008), 25.8% versus FIB-4 (p=0.002), and 19.5% versus APRI (p=0.011) (\u003cstrong\u003eFig\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;2B\u003c/strong\u003e).As shown in \u003cstrong\u003eFigure\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2D\u003c/strong\u003e, the model predicted that the probability of male patients over 30 years of age with HBV DNA negativity and an LSM greater than 6.4 kPa having\u0026nbsp;EHI\u0026nbsp;in the liver tissues reached 72.8%,greater than the percentage of female patients with positive HBV DNA and an LSM less than 6.4 kPa (6.9%), while the percentage of other patients with significant liver tissue fibrosis was 40.1%; the differences in these percentages was significant (\u0026chi;\u003csup\u003e2\u003c/sup\u003e =25.9, P \u0026lt; 0.001).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e This study included 231 IHC individuals, adhering to the standards outlined in the Chinese Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2019 Edition). Both the HBV DNA-negative group(\u0026lt;\u0026thinsp;20 IU/ml) and the positive group(20-2000 IU/ml)exhibited significant risks of liver inflammation or fibrosis, with an overall incidence rate of EHI at 35.9%, and a proportion of F\u0026thinsp;≧\u0026thinsp;2 recorded at 29%. Notably, the prevalence of significant fibrosis in the HBV DNA-negative group was markedly higher (42.2%) compared to that in the positive group (21.6%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). This disparity was particularly pronounced among individuals over the age of 30, indicating that age-related immune senescence mechanisms may play a critical role in the fibrotic progression observed in HBV DNA-negative patients. Prolonged interactions between the virus and host could lead to immune senescence phenotypes, such as T-cell exhaustion\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e, which diminishes immune surveillance capacity and ultimately contributes to the pathological characteristic of \"low viral load-high fibrosis.\"\u003c/p\u003e \u003cp\u003eThe determination of staging in the natural history of chronic HBV infection is crucial for establishing antiviral treatment indications in clinical practice. Before 2022, neither domestic nor international guidelines\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e recommended antiviral therapy for IHC patients. However, it was stated that chronic HBV-infected individuals with EHI, as determined by liver biopsy, should receive antiviral intervention. This suggests that without a liver histological assessment, about 36% of eligible patients would miss out on treatment opportunities.Notably, the 2022 Chinese guidelines\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e introduced significant changes to IHC staging criteria: Patients with HBsAg\u0026thinsp;\u0026lt;\u0026thinsp;1000 IU/mL and positive HBV DNA levels between 20-2000 IU/mL are now classified as being in a \"gray zone\" and are included within the scope for antiviral treatment. This revision not only encompasses patients who have not undergone pathological examination but also those already showing histological indications for therapy. It marks an important advancement in expanding treatment criteria for chronic HBV infection and promoting proactive interventions in China.\u003c/p\u003e \u003cp\u003eCurrently, antiviral treatment is not recommended for IHC individuals with negative HBV DNA levels; however, it remains unclear if this correlates with milder liver damage. Research shows that 44.6% of patients in the negative group presented with EHI\u0026mdash;a significantly higher rate\u0026mdash;while those scoring S\u0026thinsp;\u0026ge;\u0026thinsp;2 were more prevalent in the negative group compared to the positive group (42.2% vs 21.6%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).In contrast, there was no significant difference between the two groups regarding G\u0026thinsp;\u0026ge;\u0026thinsp;2 scores, recorded at 13.3% and 18.2%, respectively (P\u0026thinsp;=\u0026thinsp;0.320). These findings suggest that negative HBV DNA may indicate a mild degree of liver inflammation; conversely, a higher proportion of individuals with negative HBV DNA exhibited S\u0026thinsp;\u0026ge;\u0026thinsp;2 scores. This aligns with the EASL Guidelines for the Prevention and Treatment of Chronic Hepatitis B published in 2017\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e, which state that low levels of HBsAg and HBV DNA reflect only a certain stage of HBV infection without accurately indicating liver tissue damage extent. Therefore, relying solely on HBV DNA to determine antiviral treatment needs in IHC patients is inadequate; without assessing liver tissue status, nearly half of newly defined IHC patients may miss potential antiviral therapy opportunities. Thus, even with negative HBV DNA results alongside low HBsAg levels and normal ALT values, clinicians must remain vigilant and investigate factors contributing to fibrosis in this subset of IHC patients.\u003c/p\u003e \u003cp\u003eAmong the IHC patients in this study, those over 30 years old made up a significant 95.2%, aligning with the established high-risk age for disease progression noted in previous research\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. In China, mother-to-child transmission is the primary mode of HBV spread\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e, which means that CHB patient ages reflect chronic HBV infection's disease course. Research\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e shows that HCC incidence among IHC patients in East Asia is about 0.2 cases per 100 person-years, while this rate has dropped by 90% in Europe and America due to differences in viral transmission and age distributions.\u003c/p\u003e \u003cp\u003eDue to clinical limitations of liver biopsy procedures, we aimed to use non-invasive diagnostic models like LSM, APRI, and FIB-4 to evaluate liver fibrosis severity within the IHC population. Our results indicated significantly higher LSM and APRI values for individuals in the S\u0026thinsp;\u0026ge;\u0026thinsp;2 group compared to those in the S\u0026thinsp;\u0026lt;\u0026thinsp;2 group. Combining LSM with gender and negative HBV DNA yielded an AUC of 0.75 for EHI, outperforming single indicators such as FIB-4, APRI, and AST/ALT (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). For male patients over 30: when LSM\u0026thinsp;\u0026gt;\u0026thinsp;6.4 kPa and HBV DNA is negative, diagnostic sensitivity for significant fibrosis increases markedly; thus antiviral treatment should be initiated.This threshold demonstrated a positive predictive value of 72.8% within the study cohort, thereby complementing the cirrhosis warning standard (LSM\u0026thinsp;≧\u0026thinsp;8.0 kPa) proposed by F. Cinque, J et al\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003eand the recommendations set forth by the EASL\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. This integration forms a complementary stepwise management scheme. Furthermore, it provides a practical decision-making tool for primary medical institutions that lack the capacity to perform biopsies.\u003c/p\u003e \u003cp\u003eCurrent evidence supports the necessity of antiviral treatment for IHC patients\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis research, through liver histology, showed that regardless of the IHC criteria used-new or old-a significant cohort has unmet treatment needs.Benefit analysis shows that the 96-week HBsAg loss rate in DNA-negative patients treated with PEG-IFNα is 51.1%, significantly higher than the positive group (38.8%,P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with a subsequent HCC incidence dropping to 0.76%\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. This \"low-virus-high-response\" phenomenon may be relate to reduced viral integration\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e and remodeled the distinct intrahepatic immune microenvironment\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. Meanwhile, in the DNA-negative state, HBV cccDNA is highly methylated, inhibiting HBx protein transcription and enhancing interferon's antiviral effects on viral replication\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. These findings provide a biological basis for using the DNA-negative state as a screening marker to identify suitable candidates for interferon treatment.\u003c/p\u003e \u003cp\u003eClinical cure, the ideal endpoint of CHB treatment, significantly enhances long-term prognosis. In non-cirrhotic populations, the recurrence rate and risk of HCC after HBsAg loss are reduced to 9.7% and 0.76%, respectively \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. Notably, IHC patients have the lowest recurrence rate at 3.3% post-clearance and show no progression to cirrhosis or HCC \u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. Additionally, HCC incidence among non-cirrhotic IHC patients drops to 0.76% \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. These findings suggest that the PEG-IFNα-2a regimen is both feasible-achieving a clinical cure rate over 44%-and safe, with end-stage liver disease incidence below 1%. Early achievement of clinical cure can maximize patient benefits\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e, highlighting the need for timely intervention based on histological characteristics observed in liver tissue.The current cross-sectional study has inherent limitations: selection bias from preferential biopsy in high-risk patients \u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e, underestimated pathological heterogeneity in this single-center cohort \u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e, and unvalidated fibrosis progression due to limited follow-up. These constraints may affect generalizability, requiring validation through prospective multi-center studies.\u003c/p\u003e \u003cp\u003eThis study highlights crucial fibrosis risk assessment needs in HBV DNA-negative IHC patients,with 44.6% meeting histological treatment criteria. A stepwise strategy integrating age, sex, and LSM is recommended. This cohort demonstrates high cure rates, low recurrence, and improved outcomes, warranting multi-center RCTs to validate immunomarker-guided strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was permitted by the ethics committee of Beijing Youan Hospital, Capital Medical University, and the procedures were in accordance with the Helsinki declaration of 1975, as revised in 1983(The Code of Ethic Approval:[2022]159)\u003c/p\u003e\n\u003cp\u003eEthics Committee approval was obtained from the Institutional Ethics Committee of Capital Medical University Beijing Youan Hospital to the commencement of the study.\u003c/p\u003e\n\u003cp\u003eClinical Trials Registration Chinese Clinical Trial Registry (ChiCTR2200061541).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest declaration:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRen Shan and Zheng Sujun were instrumental in the conception of the study. Zhang Xinyang was responsible for collecting the pathological data, while Ma Lina and Zheng Yanhong gathered the clinical data. Fan Rongshan, Ruan Qingfa, Huang Wenqi, and other physicians from Shenzhen Third People\u0026apos;s Hospital, along with Gao Haibing, Xue Xiulan, and Yang Fang, contributed clinical and pathological data of IHC patients from their respective hospitals as part of the \u0026apos;STARHB\u0026apos; real-world study. Ren Shan and Zhang Xinyang played a significant role in the analysis and manuscript preparation. Ren Shan, Zheng Sujun, and Chen Xinyue performed the data analyses and wrote the manuscript. Chen Xinyue and Ren Shan also contributed to the analysis with insightful and constructive discussions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful to all the subjects who participated in this study. This work was supported by the National Key Research and Development Program of Ministry of Science and Technology(2023YFC2308100),\u0026nbsp;Capital Clinical Diagnostic Techniques and Translational Application Projects (Z211100002921059), The STARHB Project (The STUDY ON TREATMENT FOR INACTIVE CARRIERS OF HEPATITIS B),High-level public health technical talents construction project of Beijing Municipal Health Commission (Academic\u0026nbsp;Leader -02-14),Capital\u0026rsquo;s Funds for Health Improvement and Research(2024-2-2184),Beijing Natural Science Foundation (No. 7222093).The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eEuropean Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol 2017;67(2):370-398. DOI:10.1016/j.jhep.2017.03.021. \u003c/li\u003e\n\u003cli\u003eTerrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018;67(4):1560-1599. DOI:10.1002/hep.29800. \u003c/li\u003e\n\u003cli\u003eChinese Society of Hepatology, Chinese Society of Infectious Diseases. Guidelines for the prevention and treatment of chronic hepatitis B (2022 version). Chin J Clin Infect Dis 2022;15(6):401-427. DOI:10.3760/cma.j.issn.1674-2397.2022.06.001. \u003c/li\u003e\n\u003cli\u003eRen S, Wang W, Lu J, et al. Effect of the change in antiviral therapy indication on identifying significant liver injury among chronic hepatitis B virus infections in the grey zone. Front Immunol 2022;13:1035923. DOI:10.3389/fimmu.2022.1035923. \u003c/li\u003e\n\u003cli\u003eLiu J, Liang W, Jing W, et al. Countdown to 2030: Eliminating hepatitis B disease, China. Bull World Health Organ 2019;97(3):230-238. DOI:10.2471/BLT.18.219469. \u003c/li\u003e\n\u003cli\u003eYuen MF, Tanaka Y, Fong DYT, et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J Hepatol 2009;50(1):80-88. DOI:10.1016/j.jhep.2008.07.023. \u003c/li\u003e\n\u003cli\u003eRaffetti E, Fattovich G, Donato F. Incidence of hepatocellular carcinoma in untreated subjects with chronic hepatitis B: A systematic review and meta-analysis. Liver Int 2016;36(9):1239-1251. DOI:10.1111/liv.13142. \u003c/li\u003e\n\u003cli\u003eEilard A, Ringlander J, Andersson ME, et al. Long-term outcome of chronic hepatitis B-histological score and viral genotype are important predictors of hepatocellular carcinoma. J Viral Hepat 2025;32(3):e70008. DOI:10.1111/jvh.70008. \u003c/li\u003e\n\u003cli\u003eKim GA, Choi SW, Han S, et al. 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DOI:10.21037/hbsn-21-228. \u003c/li\u003e\n\u003cli\u003eReina-Campos M, Monell A, Ferry A, et al. Tissue-resident memory CD8 T cell diversity is spatiotemporally imprinted. Nature 2025;639:483-492. DOI:10.1038/s41586-024-08466-x. \u003c/li\u003e\n\u003cli\u003eMu D, Yuan FC, Chen Y, et al. Baseline value of intrahepatic HBV DNA over cccDNA predicts patient\u0026rsquo;s response to interferon therapy. Sci Rep 2017;7:5937. DOI:10.1038/s41598-017-05242-y. \u003c/li\u003e\n\u003cli\u003eChon YE, Kim DJ, Kim SG, et al. An observational, multicenter, cohort study evaluating the antiviral efficacy and safety in Korean patients with chronic hepatitis B receiving pegylated interferon-alpha 2a (pegasys): TRACES study. Medicine (Baltimore) 2016;95(14):e3026. DOI:10.1097/MD.0000000000003026. \u003c/li\u003e\n\u003cli\u003eSun J, Ding H, Chen G, et al. Sustained serological and complete responses in HBeAg-positive patients treated with peginterferon alfa-2b: a 6-year long-term follow-up of a multicenter, randomized, controlled trial in China. BMC Gastroenterol 2019;19(1):65. DOI:10.1186/s12876-019-0981-5. \u003c/li\u003e\n\u003cli\u003eWu Y, Liu Y, Lu J, et al. Durability of interferon-induced hepatitis B surface antigen seroclearance. Clin Gastroenterol Hepatol 2020;18(2):514-516.e2. DOI:10.1016/j.cgh.2019.04.020. \u003c/li\u003e\n\u003cli\u003eFusai GK, Tamburrino D, Partelli S, et al. Portal vein resection during pancreaticoduodenectomy for pancreatic neuroendocrine tumors: an international multicenter comparative study. Surgery 2021;169(5):1093-1101. DOI:10.1016/j.surg.2020.11.015. \u003c/li\u003e\n\u003cli\u003eLiu JK, Kam LY, Huang DQ. Racial and ethnic disparities in characteristics and care patterns of chronic hepatitis B patients in the United States. Clin Gastroenterol Hepatol 2023;21(10):2606-2615.e7. DOI:10.1016/j.cgh.2023.01.035. \u003c/li\u003e\n\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":"virology-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"virj","sideBox":"Learn more about [Virology Journal](http://virologyj.biomedcentral.com/)","snPcode":"12985","submissionUrl":"https://submission.nature.com/new-submission/12985/3","title":"Virology Journal","twitterHandle":"@VirologyJ","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Chronic hepatitis B, Inactive HBsAg carriers, Liver histopathology, Antiviral thresholds, Fibrosis, Non-invasive biomarkers","lastPublishedDoi":"10.21203/rs.3.rs-6729956/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6729956/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cb\u003eBackground\u003c/b\u003e The definition of inactive HBsAg carriers (IHC) varies globally, particularly regarding HBV DNA thresholds. Whether HBV DNA negativity reliably predicts histological quiescence remains uncertain.\u003c/p\u003e \u003cp\u003e \u003cb\u003eAims\u003c/b\u003e This study evaluated liver pathology in IHC patients to reassess antiviral therapy thresholds.\u003c/p\u003e \u003cp\u003e \u003cb\u003eMethods\u003c/b\u003e This multi-center, retrospective study included 231IHCs(2018\u0026ndash;2023) stratified by HBV DNA negativity (\u0026lt;\u0026thinsp;20IU/mL). Liver biopsies assessed inflammation (G\u0026thinsp;\u0026ge;\u0026thinsp;2) and fibrosis (F\u0026thinsp;\u0026ge;\u0026thinsp;2); evident hepatic injury (EHI) was defined as G\u0026thinsp;\u0026ge;\u0026thinsp;2 and/or F\u0026thinsp;\u0026ge;\u0026thinsp;2. Multivariable models evaluated predictors.\u003c/p\u003e \u003cp\u003e \u003cb\u003eResults\u003c/b\u003e Among 231 IHC patients(median age:43 years old; 95.2% \u0026ge;30 years old), 35.9%(83/231) were HBV DNA negative. The median HBsAg and HBV DNA level were 132 IU/ml and 94 IU/ml,respectively.Notably, EHI prevalence was significantly higher in HBV DNA negative patients than positive ones(44.9% vs. 31%, P\u0026thinsp;=\u0026thinsp;0.04), driven by fibrosis (F\u0026thinsp;\u0026ge;\u0026thinsp;2: 42.2% vs. 21.6%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), challenging the assumption that HBV DNA negativity ensures low histological risk. Male sex, HBV DNA negativity, and elevated liver stiffness measurement(LSM) independently predicted EHI (OR\u0026thinsp;=\u0026thinsp;3.37, AUC\u0026thinsp;=\u0026thinsp;0.747).\u003c/p\u003e \u003cp\u003eConclusion:\u003c/p\u003e \u003cp\u003eHBV DNA negativity does not guarantee histological quiescence in inactive HBsAg carriers aged\u0026thinsp;\u0026ge;\u0026thinsp;30 years, with 44.9% exhibiting significant liver injury. In this population, LSM\u0026thinsp;\u0026gt;\u0026thinsp;6.4 Kpa should prompt consideration of liver biopsy and/or initiation of antiviral therapy.\u003c/p\u003e","manuscriptTitle":"Reevaluating Antiviral Thresholds in HBV DNA-Negative Inactive HBsAg Carriers: A Multicenter Histopathological Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-03 07:35:04","doi":"10.21203/rs.3.rs-6729956/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-14T02:26:56+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-10T15:52:52+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-07T07:27:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"208424912329705189473424106354163284610","date":"2025-06-03T23:14:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"188910112552832769588842250900860892259","date":"2025-06-02T16:22:26+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-29T15:40:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-26T09:26:07+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-26T08:03:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"Virology Journal","date":"2025-05-23T06:36:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"virology-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"virj","sideBox":"Learn more about [Virology Journal](http://virologyj.biomedcentral.com/)","snPcode":"12985","submissionUrl":"https://submission.nature.com/new-submission/12985/3","title":"Virology Journal","twitterHandle":"@VirologyJ","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c186f1fd-c93c-43c2-b3ae-e4678c98178a","owner":[],"postedDate":"June 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-14T15:58:25+00:00","versionOfRecord":{"articleIdentity":"rs-6729956","link":"https://doi.org/10.1186/s12985-025-02853-0","journal":{"identity":"virology-journal","isVorOnly":false,"title":"Virology Journal"},"publishedOn":"2025-07-10 15:56:52","publishedOnDateReadable":"July 10th, 2025"},"versionCreatedAt":"2025-06-03 07:35:04","video":"","vorDoi":"10.1186/s12985-025-02853-0","vorDoiUrl":"https://doi.org/10.1186/s12985-025-02853-0","workflowStages":[]},"version":"v1","identity":"rs-6729956","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6729956","identity":"rs-6729956","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}