Association Between Changes in HBsAb Levels and Hepatic Adverse Events After HBsAg Clearance in Non-Cirrhotic Chronic Hepatitis B Patients

Association Between Changes in HBsAb Levels and Hepatic Adverse Events After HBsAg Clearance in Non-Cirrhotic Chronic Hepatitis B Patients | 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 Association Between Changes in HBsAb Levels and Hepatic Adverse Events After HBsAg Clearance in Non-Cirrhotic Chronic Hepatitis B Patients Wen Deng, Xiaoxue Chen, Ziyu Zhang, Xinxin Li, Weihua Cao, Yaqin Zhang, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7111922/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Objective The relationship between changes in hepatitis B surface antibody (HBsAb) levels and hepatic adverse events after hepatitis B surface antigen (HBsAg) clearance remains unclear. This study aimed to investigate the correlation between HBsAb level changes and hepatic adverse events in non-cirrhotic patients following HBsAg clearance. Methods We retrospectively analyzed patients with HBsAg seroclearance achieved via pegylated interferon-alpha (Peg-IFNα) therapy in the Department of Hepatology II at Beijing Ditan Hospital, Capital Medical University, from October 2008 to December 2023. Participants were stratified by baseline HBsAb levels into negative (<10 mIU/mL), low (10–100 mIU/mL), medium (100–1000 mIU/mL), and high (≥1000 mIU/mL) groups. Based on HBsAb trends during follow-up, patients were categorized into declining, stable, and rising groups. The primary endpoint was the incidence of hepatic adverse events after HBsAg clearance. Results A total of 390 patients were included, with a median age of 38.00 (32.00–44.00) years and median follow-up of 53.50 (11.00–173.00) months. During follow-up, 4 cases of hepatic adverse events occurred, all in the declining group (4 cases, 3.05%), while none were observed in the stable or rising groups ( P = 0.017). Changes in HBsAb levels were inversely correlated with the incidence of hepatic adverse events ( rs = -0.125, P = 0.014). Conclusion Declining HBsAb levels after HBsAg clearance may be associated with an increased risk of hepatic adverse events. Chronic Hepatitis B Hepatitis B Surface Antigen (HBsAg) Hepatitis B Surface Antibody (HBsAb) Pegylated Interferon-alpha (PEG-IFNα) Figures Figure 1 Figure 2 Introduction Chronic hepatitis B virus (HBV) infection remains a major global public health concern and is a leading cause of liver cirrhosis, hepatocellular carcinoma (HCC), and hepatic decompensation [ 1 , 2 ] . To minimize the risk of adverse hepatic outcomes in HBV-infected individuals, both domestic and international guidelines recommend functional cure—defined as hepatitis B surface antigen (HBsAg) seroclearance with or without hepatitis B surface antibody (HBsAb) seroconversion, undetectable HBV DNA, and loss of hepatitis B e antigen (HBeAg)—as the ideal clinical treatment endpoint [ 1 , 3 , 4 ] . Although HBsAg seroclearance significantly reduces the incidence of liver-related complications such as cirrhosis and HCC in clinical practice, some patients may still develop these outcomes [ 5 , 6 ] . To date, the factors influencing adverse liver events after HBsAg seroclearance remain incompletely understood. Hepatitis B surface antibody (HBsAb), a protective antibody, provides long-term immune protection by mediating the clearance of circulating HBsAg and viral particles, and it may contribute to the durability of HBsAg seroclearance after treatment withdrawal [ 7 ] . However, the correlation between HBsAb levels and the occurrence of adverse liver events following HBsAg seroclearance remains unclear. This study aims to explore the relationship between HBsAb levels, their dynamic changes during post-treatment follow-up, and the incidence of adverse hepatic events in patients who achieved HBsAg seroclearance through interferon-based therapy. The findings may provide predictive indicators for long-term outcomes following functional cure. Materials and Methods Research Subjects Patients who achieved HBsAg seroclearance following pegylated interferon-alpha (Peg-IFNα) therapy at the Liver Disease Center of Beijing Ditan Hospital, Capital Medical University, between 2008 and 2023 were included. We had access to information that could identify individual participants during data collection. Inclusion Criteria: (1) HBsAg < 0.05 IU/mL, HBV DNA < 20 IU/mL, and HBeAg negativity after Peg-IFNα treatment; (2) Post-treatment follow-up duration ≥ 48 weeks after HBsAg seroclearance and discontinuation of therapy;(3) Age 18–65 years. Exclusion Criteria: (1) Coexisting liver diseases, including hepatitis A, B, D, or E, alcoholic hepatitis, autoimmune hepatitis, metabolic hepatitis, or non-alcoholic fatty liver disease; (2) Concurrent infections with other viruses causing liver injury, such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), or human immunodeficiency virus (HIV); (3) Presence of cirrhosis at the time of HBsAg seroclearance (defined as a Fibrosis Index Based on 4 factors [FIB-4] score ≥ 3.25); (4) Diagnosis of malignancies at enrollment. This study was approved by the Ethics Committee of Beijing Ditan Hospital, Capital Medical University (Approval No.: Jing Di Lun Yan Zi [2023] No. (009)-01) and registered at ClinicalTrials.gov (ID: NCT04301908; registration date: 03/06/2020; https://register.clinicaltrials.gov/). This was a retrospective study, and the ethics committee waived the requirement for informed consent. Data Collection Data were collected through the Hospital Information System (HIS) and Laboratory Information System (LIS), including patients' demographic data (age, gender), treatment information (antiviral treatment regimens, discontinuation time), baseline data at Peg-IFNα treatment cessation (HBsAb levels, HBV DNA levels, liver function, imaging results, etc., at the time of HBsAg seroclearance and treatment discontinuation), endpoint follow-up data (time and type of liver-related adverse events, or last follow-up date), liver function parameters, HBV virological and serological indicators assessed every 3–6 months during follow-up, and hepatic imaging results evaluated every 6–12 months. Patients in this study were stratified according to baseline HBsAb levels into four groups: negative (<10 mIU/mL), low (≥10 and <100 mIU/mL), medium (≥100 and <1000 mIU/mL), and high (≥1000 mIU/mL). Additionally, based on changes in HBsAb levels from HBsAg seroclearance (treatment discontinuation) to the end of follow-up, patients were divided into three groups: Decline group (downgrade in HBsAb level category), Stable group (no change in HBsAb level category), Rise group (upgrade in HBsAb level category). Laboratory Testing All clinical biochemical and virological indicators were measured at the Clinical Laboratory Center of Beijing Ditan Hospital. HBsAg and HBsAb levels were determined using the Abbott microparticle chemiluminescence immunoassay (Abbott Laboratories, USA; Abbott i2000 automated immunoassay analyzer). The upper detection limits were HBsAg >250 IU/mL and HBsAb >1000 mIU/mL, with HBsAb ≥10 mIU/mL defined as HBsAb positivity. HBV DNA was quantified using fluorescent quantitative polymerase chain reaction (Roche, Switzerland; Light Cycler 480 PCR system), with a lower detection limit of 20 IU/mL. Liver function tests were performed using the Hitachi 7180 automated biochemical analyzer. Hepatocellular carcinoma (HCC) and cirrhotic ascites were assessed via color Doppler flow imaging (Siemens, USA; ACUSON X150), computed tomography (Siemens, USA; SOMATOM Definition AS), or magnetic resonance imaging (Siemens, USA; MAGNETOM Skyra). Data analysis The incidence of liver-related adverse events (cirrhotic ascites, liver failure, upper gastrointestinal bleeding, and HCC) following HBsAg clearance. Statistical Analysis Data were analyzed using SPSS 19.0 and visualized with GraphPad Prism. Normally distributed continuous data are presented as mean ± standard deviation and compared using ANOVA or an independent samples t-test. Non-normally distributed continuous data are expressed as median (interquartile range) and analyzed with the Mann-Whitney U test. Paired samples were compared using the paired t-test or the Wilcoxon signed-rank test for non-normal data. Categorical data are reported as frequency (percentage) and analyzed with the chi-square test. Correlation analyses included: Point-biserial correlation for binary categorical vs. non-normal continuous variables; Phi coefficient for two binary categorical variables; Spearman’s rank correlation for categorical vs. ordinal variables, two ordinal variables, or ordinal vs. continuous variables. All statistical tests were two-tailed, with significance defined as α = 0.05. Results Demographic Data of Patients A total of 645 patients who achieved HBsAg seroclearance after Peg-IFNα therapy were enrolled. Of these, 189 were excluded due to follow-up durations <48 weeks, 20 due to missing HBsAb results at the study endpoint, and 46 due to baseline cirrhosis. Ultimately, 390 patients were included in the analysis. The median age at the time of HBsAg seroclearance and treatment discontinuation was 38.00 (interquartile range: 32.00, 44.00) years, with a median follow-up duration of 53.50 (range: 11.00–173.00 months). Baseline HBsAb Level Grouping Data Patients were stratified into four groups based on baseline HBsAb levels: negative group (n=70), low-level group (n=112), intermediate-level group (n=165), and high-level group (n=43). The median ages at HBsAg clearance and treatment discontinuation were 42.50 (37.00, 47.00), 38.00 (33.25, 44.00), 37.00 (32.00, 42.00), and 33.00 (29.00, 40.00) years, respectively, with statistically significant differences among the groups (H = 28.519, P < 0.001). A correlation analysis between baseline HBsAb levels and age at HBsAg seroclearance revealed a weak negative correlation (rs = -0.248, P < 0.001). The correlation coefficient matrix for all variables is shown in Table 1. Table 1. Correlation Matrix of the Variables Variable Age Male ALT abnormal b AST abnormal b TBIL abnormal b ALB abnormal b HGB abnormal b PLT abnormal b ALT abnormal e AST abnormal e TBIL abnormal e ALB abnormal e HGB abnormal e PLT abnormal e Adverse events Liver cirrhosis e HBsAb level classification b Male 0.127* ALT abnormal b -0.120* -0.059 AST abnormal b -0.119* -0.083 0.381** TBIL abnormal b -0.024 0.075 -0.003 -0.033 ALB abnormal b 0.092 -0.019 -0.021 0.025 0.041 HGB abnormal b -0.076 -0.101* 0.025 -0.015 0.006 0.056 PLT abnormal b 0.117* 0.266** 0.107 -0.011 0.023 -0.005 0.094 ALT abnormal e -0.002 0.173** 0.144** 0.042 0.075 -0.015 -0.056 0.081 AST abnormal e 0.046 0.077 0.119* 0.148** 0.007 0.065 0.006 0.001 0.307** TBIL abnormal e 0.031 0.164** -0.080 -0.007 0.229** 0.029 0.034 0.093 0.041 -0.022 ALB abnormal e -0.065 -0.191** -0.040 -0.028 -0.038 -0.022 0.098 -0.015 -0.100 -0.031 -0.071 HGB abnormal e -0.024 -0.167** 0.111* -0.055 0.010 0.069 0.263** 0.041 0.025 -0.039 -0.052 0.062 PLT abnormal e 0.057 0.071 -0.028 -0.020 0.010 0.167* 0.054 0.135* 0.176** 0.033 0.093 -0.030 0.037 Adverse events 0.045 -0.041 -0.015 0.018 -0.025 -0.015 -0.038 -0.003 -0.011 -0.020 0.020 -0.016 -0.020 0.254** Liver cirrhosis e 0.103* -0.067 -0.042 0.035 -0.022 0.194 0.056 0.080 0.135* -0.018 0.114 -0.014 0.141 0.456** 0.282* HBsAb level classification b -0.248** -0.033 0.124* 0.123* -0.014 -0.036 -0.039 0.032 0.050 0.100* -0.015 0.106* -0.058 0.022 0.083 0.048 Changes in HBsAb stratification -0.010 -0.015 -0.041 -0.028 -0.005 -0.035 0.021 -0.001 0.026 -0.034 0.059 -0.119* 0.071 -0.020 -0.125* -0.032 -0.454** Note : The superscript letter "b" indicates data at baseline/HBsAg clearance discontinuation, and the superscript letter "e" indicates data at the endpoint/follow-up conclusion. ALT abnormalityᵇ, AST abnormalityᵇ, TBIL abnormalityᵇ, ALB abnormalityᵇ, HGB abnormalityᵇ, and PLT abnormalityᵇ denote data at HBsAg clearance discontinuation. ALT abnormalityᵉ, AST abnormalityᵉ, TBIL abnormalityᵉ, ALB abnormalityᵉ, HGB abnormalityᵉ, and PLT abnormalityᵉ denote data at follow-up conclusion. HBsAb grading refers to categorization based on baseline HBsAb levels, while HBsAb grading change is categorized according to the shift in HBsAb levels from baseline to endpoint. P value: ** denotes significant correlation at the 0.01 level (two-sided); * indicates significant correlation at the 0.05 level (two-sided). Baseline ALT abnormality rates showed no significant differences among the four groups [35 (50.00%) vs. 58 (51.78%) vs. 100 (60.61%) vs. 30 (69.77%), χ² = 6.379, P = 0.095], whereas baseline AST abnormality rates differed significantly [9 (12.86%) vs. 17 (15.18%) vs. 31 (18.79%) vs. 14 (32.56%), χ² = 8.020, P = 0.046]. Correlation analysis between baseline HBsAb levels and ALT/AST abnormality rates at HBsAg clearance cessation revealed a weak positive association (rs = 0.124, P = 0.014; rs = 0.123, P = 0.015). Other baseline liver function parameters—TBIL, HGB, PLT, and ALB—showed no significant intergroup differences ( P > 0.05). The overall follow-up duration was 53.50 (11.00–173.00) months, with no significant differences among the negative, low-, moderate-, and high-level groups [50.50 (12.00–173.00), 46.50 (12.00–164.00), 59.00 (12.00–160.00), and 60.00 (11.00–118.00) months, respectively; H = 3.689, P = 0.297]. Endpoint ALT, AST, TBIL, ALB, HGB, and PLT levels also showed no significant intergroup differences ( P > 0.05). By the end of follow-up, 4 patients developed hepatic adverse events (2 HCC, 2 ascites). The incidence rates were 0.00% (0/70) in the negative group, 0.89% (1/112) in the low-level group, 0.61% (1/165) in the moderate-level group, and 4.65% (2/43) in the high-level group, with no statistical significance (χ² = 4.471, P = 0.143). Additionally, 3 patients developed cirrhosis, with no significant intergroup differences in incidence [0.00% (0/70) vs. 0.89% (1/112) vs. 0.61% (1/165) vs. 2.33% (2/43); χ² = 2.271, P = 0.513]. Detailed patient characteristics are shown in Table 2. Table 2. Patient Characteristics by Baseline HBsAb Levels Variable All patients (n=390) Negative group(n=70) low-level group (n=112) moderate-level group (n=165) high-level group (n=43) χ2 / H P Male (n, %) 268(68.72%) 48(68.57%) 79(70.54%) 115(69.70%) 26(60.47%) 1.609 0.657 Age (years) 38.00(32.00,44.00) 42.50(37.00,47.00) 38.00(33.25,44.00) 37.00(32.00,42.00) 33.00(29.00,40.00) 28.519 ＜0.001 Adverse events (n, %) 4(1.03%) 0(0%) 1(0.89%) 1(0.61%) 2(4.65%) 4.471 0.143 ALT abnormal b (n, %) 223(57.18%) 35(50.00%) 58(51.78%) 100(60.61%) 30(69.77%) 6.379 0.095 AST abnormal b (n, %) 71(18.21%) 9(12.86%) 17(15.18%) 31(18.79%) 14(32.56%) 8.02 0.046 TBIL abnormal b (n, %) 23(5.90%) 5(7.14%) 5(4.46%) 12(7.27%) 1(2.33%) 1.881 0.576 ALB abnormal b (n, %) 8(2.05%) 2(2.86%) 3(2.68%) 2(1.21%) 1(2.33%) 1.645 0.680 HGB abnormal b (n, %) 48(12.31%) 9(12.86%) 16(14.29%) 19(11.52%) 4(9.30%) 0.881 0.830 PLT abnormal b (n, %) 103(26.41%) 16(22.86%) 27(24.11%) 52(31.52%) 8(18.60%) 4.321 0.230 ALT abnormal e (n, %) 116(29.74%) 20(28.57%) 31(27.68%) 48(29.10%) 17(39.53%) 2.281 0.516 AST abnormal e (n, %) 15(3.85%) 0(0%) 4(3.57%) 8(4.85%) 3(6.98%) 4.885 0.152 TBIL abnormal e (n, %) 68(17.44%) 15(21.43%) 17(15.18%) 28(16.97%) 8(18.60%) 1.237 0.756 ALB abnormal e (n, %) 9(2.31%) 0(0%) 2(1.79%) 4(2.42%) 3(6.98%) 4.867 0.130 HGB abnormal e (n, %)) 14(3.59%) 5(7.14%) 2(1.79%) 7(4.24%) 0(0%) 4.644 0.157 PLT abnormal e (n, %) 14(3.59%) 2(2.86%) 4(3.57%) 6(3.64%) 2(4.65%) 0.504 0.935 Liver cirrhosis e (n, %) 3(0.77%) 0(0%) 1(0.89%) 1(0.61%) 1(2.33%) 2.271 0.513 Note: P < 0.05 indicates a statistically significant difference. Groups were defined as follows: Negative group (HBsAb <10 mIU/mL), low-level group (HBsAb ≥10 mIU/mL and <100 mIU/mL), moderate-level group (HBsAb ≥100 mIU/mL and <1000 mIU/mL), and high-level group (HBsAb ≥1000 mIU/mL). Changes in HBsAb During Follow-up and the Occurrence of Adverse Events Based on changes in HBsAb levels during the follow-up period, the study population was divided into three groups: a decline group (131 cases), a stable group (154 cases), and an increase group (105 cases). The incidence of liver-related adverse events during follow-up in the HBsAb decline, stable, and increase groups was 3.05% (4/131), 0.00% (0/154), and 0.00% (0/105), respectively, showing a statistically significant difference (χ² = 5.694, P = 0.017). Correlation analysis between HBsAb level changes and liver-related adverse event incidence revealed a weak but statistically significant negative correlation (rs = -0.125, P = 0.014). At the end of follow-up, a total of 3 patients developed liver cirrhosis, with no significant differences observed among the HBsAb decline, stable, and increase groups [1.53% (2/131) vs. 0.00% (0/154) vs. 0.95% (1/105); χ² = 2.266, P = 0.367]. Additionally, baseline and endpoint liver function indicators (ALT, AST, TBIL, ALB), hemoglobin (HGB) levels, and platelet (PLT) counts showed no significant differences among the three groups. Detailed patient characteristics are presented in Figure 1. Abnormal Transaminase Levels During Follow-up and the Development of Liver Cirrhosis Neither baseline HBsAb levels nor changes in HBsAb levels during follow-up had a significant impact on the development of liver cirrhosis. By the end of follow-up, only 3 patients had progressed to cirrhosis. Therefore, we further investigated the association between transaminase levels and cirrhosis development. The incidence of endpoint cirrhosis showed no significant difference between patients with normal and abnormal baseline ALT levels [1.98% (2/167) vs. 0.45% (1/223), Fisher's exact test, P = 0.579] or between those with normal and abnormal baseline AST levels [0.63% (2/319) vs. 1.41% (1/71), Fisher's exact test, P = 0.454]. However, a significant difference was observed in endpoint cirrhosis incidence between patients with normal and abnormal endpoint ALT levels [0.00% (0/274) vs. 2.59% (3/116), Fisher's exact test, P = 0.026], though no such difference existed for endpoint AST levels [0.80% (3/375) vs. 0% (0/15), Fisher, P > 0.999]. Analysis of the correlation between endpoint cirrhosis incidence and endpoint ALT abnormality rates revealed a weak positive association (rs = 0.135, P = 0.026). Discussion Globally, over 325 million people are chronically infected with hepatitis B virus (HBV). Despite the availability of effective vaccines, nearly 1 million individuals die annually from HBV-related complications [ 8 ] . Chronic HBV infection significantly increases the risk of developing advanced liver diseases, and hepatocellular carcinoma (HCC) is closely associated with HBV infection. It is estimated that approximately 830,000 people worldwide die from liver cancer annually, with 906,000 new cases reported each year [ 9 ] . In the Asia-Pacific region, primary liver cancer has the highest incidence rate, ranking as the second leading cause of cancer-related death and the fifth most prevalent cancer type [ 9 ] . In patients with chronic HBV infection, long-term antiviral therapy with nucleos(t)ide analogues (NAs) can effectively suppress HBV DNA replication, reverse liver fibrosis and cirrhosis, and reduce the incidence of liver-related adverse events such as HCC and cirrhosis complications. However, the serological clearance of hepatitis B surface antigen (HBsAg) remains rare [ 10 , 11 ] . HBsAg clearance reduces the risk of hepatic decompensation and HCC. Pegylated interferon-alpha (Peg-IFNα) treatment has been shown to enhance HBsAg seroconversion rates by modulating immune responses, including HBV-specific B lymphocytes and cytotoxic T lymphocytes (CTLs) [ 12 ] . CD8-positive T lymphocytes (CD8+ T cells) are critical for controlling HBV infection in the liver by eliminating infected hepatocytes [ 13 ] . Single-cell sequencing of peripheral blood has revealed that HBV polymerase 455 (HBV pol455)-specific CD8+ T cells with cytotoxic features—characterized by high expression of granulysin (GNLY), granzyme B (GZMB), perforin 1 (PRF1), and natural killer cell granule protein 7 (NKG7)—are associated with intrinsic HBV control[ 14 ]. During chronic infection, virus-specific CD8+ T cells often become dysfunctional and fail to clear infected hepatocytes [ 15 , 16 , 17 ] .In patients achieving HBsAg clearance, single-cell sequencing of liver samples demonstrates a significant reduction in exhausted CD8+ T cells expressing programmed death-1 (PD1+), T-cell immunoglobulin and mucin-domain containing-3 (TIM3+), and lymphocyte-activation gene-3 (LAG3+) [ 18 ] . These findings suggest that although CD8+ T cells may become functionally exhausted during chronic infection, their activity can be restored upon HBsAg clearance, highlighting their pivotal role in antiviral immunity. B lymphocytes play a key role in initiating antiviral immune responses following HBV exposure. Early-activated B cells exhibit upregulated expression of major histocompatibility complex class II (MHC-II), C-X-C motif chemokine receptor 5 (CXCR5), and PD-1, which are closely associated with B cell activation and immune regulation. Peg-IFNα therapy induces an increase in B cell levels, particularly plasmablasts (CD19+CD38+), which inversely correlate with hepatitis B antigen levels [ 19 ] . HBV recovery typically involves two seroconversion events: HBsAg loss accompanied by HBsAb emergence, and HBeAg loss with HBeAb seroconversion. B cells are believed to play a central role in this process [ 19 ] .Activated B cells rapidly produce specific antibodies, providing robust immune protection [ 20 , 21 ] . HBsAb facilitates the clearance of HBV-infected cells through antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) [ 22 , 23 ] . Thus, HBsAb positivity typically indicates HBV recovery and HBsAg clearance. However, the relationship between HBsAb and post-treatment liver-related adverse events following HBsAg seroconversion remains unclear. The inhibitory effect of HBsAb on HBV infection is illustrated in Figure 2. In this study, the age at HBsAg seroclearance and treatment discontinuation differed significantly among groups with varying HBsAb levels, indicating that higher HBsAb levels were associated with younger ages at treatment discontinuation. HBsAb is secreted by HBV-specific B cells, and its level is closely related to the functional activity of B-cell immunity. During HBV infection, the generation and function of antigen-specific memory B cells are critical for pathogen clearance and long-term immune control [ 24 ] . However, B-cell production capacity gradually declines with age, resulting in weakened immune function [ 24 ] . This age-related immune decline may explain the negative correlation between HBsAb levels and discontinuation age (rs = -0.248, P < 0.001). HBsAb levels are closely linked to immune activity. Active immune attacks on residual viruses or infected hepatocytes may cause hepatocellular damage, elevating AST and ALT levels [ 25 , 26 ] . Studies indicate that during peg-IFNα therapy for CHB, elevated transaminase levels are significantly associated with higher HBsAg clearance rates [ 27 , 28 ] . Our study found significant differences in abnormal ALT and AST rates among HBsAb-level groups, with higher HBsAb levels associated with increased ALT and AST abnormalities (rs = 0.124, P = 0.014; rs = 0.123, P = 0.015). ALT and AST are key markers for liver function assessment, and ALT is generally considered more directly linked to hepatic activity [ 29 ] . The observed association between high HBsAb levels and elevated AST in this study may suggest stronger immune activation in patients receiving peg-IFNα therapy. In this study, although the occurrence of liver-related adverse events was not associated with baseline HBsAb levels, a significant negative correlation was observed with dynamic changes in HBsAb levels during follow-up (rs = -0.125, P = 0.014). Notably, a decline in HBsAb level category corresponded to an increased incidence of hepatic adverse events. Among the cohort, four HBsAg-serocleared patients who discontinued treatment experienced liver-related adverse events during follow-up, all occurring in the HBsAb-declining subgroup. HBsAb-specific B cells have been identified as valuable predictive biomarkers for HBsAg seroconversion in treatment-naïve chronic HBV-infected patients [ 30 ] . For those who achieved HBsAg clearance, previous studies demonstrated that HBsAb levels influence the durability of peg-IFNα-induced HBsAg loss [ 7 , 31 , 32 ] . However, regarding hepatic adverse events, existing research indicates that serological conversion status does not affect the risk of such events [ 33 ] , consistent with our findings that post-HBsAg clearance, HBsAb levels lack direct correlation with adverse event occurrence. Although baseline antibody levels may partially predict post-HBsAg-clearance relapse, they likely fail to comprehensively reflect dynamic immune system changes or complex virus-host interactions. In contrast, longitudinal HBsAb level alterations directly mirror immune response activity. Our data revealed a significant negative correlation between declining HBsAb levels and liver adverse events, with all four adverse event cases clustered in the HBsAb-declining subgroup. These findings suggest that waning HBsAb levels may weaken immune protection, potentially increasing the risk of viral reactivation or hepatocellular injury. ALT, a sensitive marker of hepatocellular damage, reflects persistent hepatic inflammation and cellular injury [ 29 ] . At the follow-up endpoint, three cirrhosis cases were identified, all occurring in patients with abnormal ALT levels. A positive correlation was observed between the incidence of cirrhosis and the rate of endpoint ALT abnormalities, with cirrhosis prevalence increasing alongside ALT abnormality (rs = 0.135, P = 0.026). Persistent ALT abnormalities indicate ongoing chronic liver injury, potentially driven by repeated hepatocyte necrosis, hyperactivation of hepatic stellate cells, and aberrant extracellular matrix deposition [ 34 ] . This chronic inflammatory microenvironment promotes fibrogenesis, ultimately leading to cirrhosis [ 35 ] . These findings highlight the importance of closely monitoring ALT abnormalities in HBsAg-serocleared patients to implement timely interventions that may decelerate cirrhotic progression and improve long-term outcomes. This study has several limitations, including a relatively small sample size and low incidence of hepatic adverse events, potentially affecting statistical power. Other confounding factors (host genetics, viral genotypes, family history) were not systematically analyzed. Furthermore, non-invasive biomarkers rather than liver biopsy (the diagnostic gold standard) were used for cirrhosis evaluation, introducing potential diagnostic inaccuracies. Future multicenter, large-scale, gold standard-based prospective studies are warranted. In HBsAg-serocleared, non-cirrhotic patients after treatment cessation, longitudinal HBsAb decline, rather than baseline HBsAb levels, may indicate increased risk of hepatic adverse events. This emphasizes the clinical importance of dynamic HBsAb monitoring to optimize long-term prognosis assessment and management strategies. Conclusion Declining HBsAb levels after HBsAg clearance may be associated with an increased risk of hepatic adverse events. Abbreviations HBsAb Hepatitis B surface antibody HBsAg Hepatitis B surface antigen Peg-IFNα Pegylated interferon-alpha HBV Hepatitis B virus HCC Hepatocellular carcinoma HBeAg Hepatitis B e antigen HIS Hospital Information System LIS Laboratory Information System ALT Alanine Aminotransferase AST Aspartate Aminotransferase TBIL Total Bilirubin ALB Albumin HGB Hemoglobin PLT Platelet Count NAs Nucleos(t)ide analogues CTLs Cytotoxic T lymphocytes CD8+ T cells CD8-positive T lymphocytes HBV pol455 HBV polymerase 455 GNLY Granulysin GZMB Granzyme B PRF1 Perforin 1 NKG7 Natural killer cell granule protein 7 PD1+ Programmed death-1 TIM3+ T-cell immunoglobulin and mucin-domain containing-3 LAG3+ Lymphocyte-activation gene-3 MHC-II Major histocompatibility complex class II CXCR5 C-X-C motif chemokine receptor 5 ADCC Antibody-dependent cell-mediated cytotoxicity ADCP Antibody-dependent cellular phagocytosis NTCP Sodium Taurocholate Cotransporting Polypeptide Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of Beijing Ditan Hospital, Capital Medical University (Approval No.: Jing Di Lun Yan Zi [2023] No. (009)-01). Written informed consent for participation was not required for this study under the national legislation and institutional requirements. Clinical Trial This study was registered at ClinicalTrials.gov (ID: NCT04301908; registration date: 03/06/2020; https://register.clinicaltrials.gov/). Consent for publication This manuscript is approved by all authors for publication. Availability of data and material All data are included in the original manuscript. Competing interests The authors declare no competing interests. Funding The Capital Health Development and Scientific Research of special public health project (BRWEP2024W102170101).The National Key Research and Development Program (2022YFC2603500, 2022YFC2603505,2023YFC2306901,2023YFC2308105); The capital health research and development of special public health project (2022-1-2172); Beijing Municipal Health Commission high-level public health technical personnel construction project(discipline leader -03-26, discipline backbone-02-28); Beijing Hospitals Authority "peak" talent training program(DFL20241803); Beijing Hospitals Authority Clinical medicine Development of special funding support (ZLRK202301). Authors' contributions DW drafted the manuscript. DW, CXX, ZZY and LXX performed the data analysis and revised the manuscript. CWH, ZYQ, WSY, YLM, WX, WSJ, GZX collected the clinical information. XY and LMH conceptualized and designed the study, interpreted the results, and critically reviewed and revised the manuscript. Acknowledgements The research was funded by the fundings: Beijing Research Ward Excellence Program (BRWEP2024W102170101). The National Key Research and Development Program (2022YFC2603500, 2022YFC2603505,2023YFC2306901,2023YFC2308105); The capital health research and development of special public health project (2022-1-2172); Beijing Municipal Health Commission high-level public health technical personnel construction project(discipline leader -03-26, discipline backbone-02-28); Beijing Hospitals Authority "peak" talent training program(DFL20241803); Beijing Hospitals Authority Clinical medicine Development of special funding support (ZLRK202301). References You H, Wang F, Li T, et al. Guidelines for the prevention and treatment of chronic hepatitis B: 2022 update. J Pract Hepatol. 2023;26(3):457–478. doi: 10.3760. Kanda T, Sasaki-Tanaka R, Tsuchiya A, et al. Hepatitis B virus infection and its treatment in Eastern Ethiopia. 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HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues. J Hepatol. 2019;70(3):361-370. doi:10.1016/j.jhep.2018.10.014. Thimme R, Wieland S, Steiger C, et al. CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection. J Virol. 2003;77(1):68-76. doi:10.1128/jvi.77.1.68-76.2003. Heim K, Sagar, Sogukpinar Ö, et al. Attenuated effector T cells are linked to control of chronic HBV infection. Nat Immunol. 2024;25(9):1650-1662. doi:10.1038/s41590-024-01928-4. Bosch M, Kallin N, Donakonda S, et al. A liver immune rheostat regulates CD8 T cell immunity in chronic HBV infection. Nature. 2024;631(8022):867-875. doi:10.1038/s41586-024-07630-7. Zhang C, Li J, Cheng Y, et al. Single-cell RNA sequencing reveals intrahepatic and peripheral immune characteristics related to disease phases in HBV-infected patients. Gut. 2023;72(1):153-167. doi:10.1136/gutjnl-2021-325915. 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A three antigen hepatitis B vaccine induces T cells to Pres1 and Pres2 which correlate with anti HBs antibody titers: An investigation into the immunological mechanisms contributing to high anti-HBs titers. Vaccine. 2025;43(Pt 2):126513. doi:10.1016/j.vaccine.2024.126513. Lu LL, Suscovich TJ, Fortune SM, et al. Beyond binding: antibody effector functions in infectious diseases. Nat Rev Immunol. 2018;18(1):46-61. doi:10.1038/nri.2017.106. Vanwolleghem T, Adomati T, Van Hees S, et al. Janssen HLA. Humoral immunity in hepatitis B virus infection: Rehabilitating the B in HBV. JHEP Rep. 2021;4(2):100398. doi:10.1016/j.jhepr.2021.100398. Cancro MP. Age-Associated B Cells. Annu Rev Immunol. 2020;38:315-340. doi:10.1146/annurev-immunol-092419-031130. Zhang JW, Lai RM, Wang LF, et al. Varied immune responses of HBV-specific B cells in patients undergoing pegylated interferon-alpha treatment for chronic hepatitis B. J Hepatol. 2024;81(6):960-970. doi:10.1016/j.jhep.2024.06.033. Seo HY, Park JY, Lee SH, et al. Clusterin inhibits lipopolysaccharide induced liver injury. Sci Rep. 2025;15(1):5975. doi:10.1038/s41598-024-80903-3. Hardtke S, Yurdaydin C, Caruntu FA, et al. Frequency, Severity and Impact of Pegylated Interferon Alpha-Associated Flares in Hepatitis D Infection. J Viral Hepat. 2025;32(4):e70022. doi:10.1111/jvh.70022. Perrillo R, Lin HS, Schwarz KB, et al. Changes in serum hepatitis B surface and e antigen, interferon-inducible protein 10, and aminotransferase levels during combination therapy of immune-tolerant chronic hepatitis B. Hepatology. 2022;76(3):775-787. doi:10.1002/hep.32400. Moriles KE, Zubair M, Azer SA. Alanine Aminotransferase (ALT) Test. 2024 Feb 27. PMID: 32644704. Yin S, Wan Y, Issa R, et al. The presence of baseline HBsAb-Specific B cells can predict HBsAg or HBeAg seroconversion of chronic hepatitis B on treatment. Emerg Microbes Infect. 2023;12(2):2259003. doi:10.1080/22221751.2023.2259003. Li M, Sun F, Bi X, et al. Consolidation treatment needed for sustained HBsAg-negative response induced by interferon-alpha in HBeAg positive chronic hepatitis B patients. Virol Sin. 2022;37(3):390-397. doi:10.1016/j.virs.2022.03.001. Pan CQ, Li MH, Yi W, et al. Outcome of Chinese patients with hepatitis B at 96 weeks after functional cure with IFN versus combination regimens. Liver Int. 2021;41(7):1498-1508. doi:10.1111/liv.14801. Yuen MF, Wong DK, Fung J, et al. HBsAg Seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma. Gastroenterology. 2008;135(4):1192-1199. doi:10.1053/j.gastro.2008.07.008. Trautwein C, Friedman SL, Schuppan D, et al. Hepatic fibrosis: Concept to treatment. J Hepatol. 2015;62(1 Suppl):S15-S24. doi:10.1016/j.jhep.2015.02.039. Martínez García de la Torre RA, Vallverdú J, Xu Z, et al. Trajectory analysis of hepatic stellate cell differentiation reveals metabolic regulation of cell commitment and fibrosis. Nat Commun. 2025;16(1):1489. doi:10.1038/s41467-025-56024-4. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 12 May, 2026 Reviews received at journal 08 May, 2026 Reviews received at journal 06 May, 2026 Reviewers agreed at journal 01 May, 2026 Reviewers agreed at journal 30 Apr, 2026 Reviews received at journal 17 Sep, 2025 Reviewers agreed at journal 05 Sep, 2025 Reviewers invited by journal 13 Aug, 2025 Editor invited by journal 18 Jul, 2025 Editor assigned by journal 17 Jul, 2025 Submission checks completed at journal 17 Jul, 2025 First submitted to journal 13 Jul, 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. 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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-7111922","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":499965970,"identity":"58e55b4e-bb3b-4d71-95d1-02b777381b9f","order_by":0,"name":"Wen Deng","email":"","orcid":"","institution":"Beijing Ditan Hospital, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wen","middleName":"","lastName":"Deng","suffix":""},{"id":499965972,"identity":"a6639f0e-5df2-4d12-8482-836b94cc898b","order_by":1,"name":"Xiaoxue Chen","email":"","orcid":"","institution":"Beijing Ditan Hospital, Capital Medical 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University","correspondingAuthor":true,"prefix":"","firstName":"Minghui","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2025-07-13 07:53:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7111922/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7111922/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89591658,"identity":"5d1fe589-055a-43f8-b28d-a59afd787c10","added_by":"auto","created_at":"2025-08-21 16:08:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":568246,"visible":true,"origin":"","legend":"\u003cp\u003ePatient Data of the HBsAb Decline, Stable, and Rise Groups\u003c/p\u003e\n\u003cp\u003eNote: Patients were categorized into three groups based on changes in HBsAb levels after discontinuation: decline group, stable group, and rise group. Left panel: Comparison of abnormal rates of clinical indicators among the three groups at treatment discontinuation; Right panel: Changes in abnormal rates of clinical indicators across the three groups by the end of follow-up.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7111922/v1/45451d59ada87a7ab072b82b.png"},{"id":89591712,"identity":"9c6cb663-4455-4824-af76-a4f0395f7cbd","added_by":"auto","created_at":"2025-08-21 16:08:41","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":3191926,"visible":true,"origin":"","legend":"\u003cp\u003eThe inhibitory effect of HBsAb on HBV infection\u003c/p\u003e\n\u003cp\u003eNote: The left panel shows HBV infecting hepatocytes via the NTCP receptor in the absence of HBsAb; the right panel illustrates that HBsAb inhibits infection by binding to viral surface antigens, thereby blocking their interaction with the NTCP receptor.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7111922/v1/edba0bfd1af02b4e3f135bf6.png"},{"id":89593159,"identity":"3f361891-46d8-431f-994e-576124b553bc","added_by":"auto","created_at":"2025-08-21 16:16:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4171166,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7111922/v1/02c5798e-b8a1-47f1-b117-b47df5d222d4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association Between Changes in HBsAb Levels and Hepatic Adverse Events After HBsAg Clearance in Non-Cirrhotic Chronic Hepatitis B Patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChronic hepatitis B virus (HBV) infection remains a major global public health concern and is a leading cause of liver cirrhosis, hepatocellular carcinoma (HCC), and hepatic decompensation\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e1\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e2\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. To minimize the risk of adverse hepatic outcomes in HBV-infected individuals, both domestic and international guidelines recommend functional cure\u0026mdash;defined as hepatitis B surface antigen (HBsAg) seroclearance with or without hepatitis B surface antibody (HBsAb) seroconversion, undetectable HBV DNA, and loss of hepatitis B e antigen (HBeAg)\u0026mdash;as the ideal clinical treatment endpoint\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e1\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e3\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e4\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e . Although HBsAg seroclearance significantly reduces the incidence of liver-related complications such as cirrhosis and HCC in clinical practice, some patients may still develop these outcomes\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e5\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e6\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. To date, the factors influencing adverse liver events after HBsAg seroclearance remain incompletely understood.\u003c/p\u003e\n\u003cp\u003eHepatitis B surface antibody (HBsAb), a protective antibody, provides long-term immune protection by mediating the clearance of circulating HBsAg and viral particles, and it may contribute to the durability of HBsAg seroclearance after treatment withdrawal\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e7\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. However, the correlation between HBsAb levels and the occurrence of adverse liver events following HBsAg seroclearance remains unclear.\u003c/p\u003e\n\u003cp\u003eThis study aims to explore the relationship between HBsAb levels, their dynamic changes during post-treatment follow-up, and the incidence of adverse hepatic events in patients who achieved HBsAg seroclearance through interferon-based therapy. The findings may provide predictive indicators for long-term outcomes following functional cure.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eResearch Subjects\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients who achieved HBsAg seroclearance following pegylated interferon-alpha (Peg-IFN\u0026alpha;) therapy at the Liver Disease Center of Beijing Ditan Hospital, Capital Medical University, between 2008 and 2023 were included. We had access to information that could identify individual participants during data collection. Inclusion Criteria: (1) HBsAg \u0026lt; 0.05 IU/mL, HBV DNA \u0026lt; 20 IU/mL, and HBeAg negativity after Peg-IFN\u0026alpha; treatment; (2) Post-treatment follow-up duration \u0026ge; 48 weeks after HBsAg seroclearance and discontinuation of therapy;(3) Age 18\u0026ndash;65 years. Exclusion Criteria: (1) Coexisting liver diseases, including hepatitis A, B, D, or E, alcoholic hepatitis, autoimmune hepatitis, metabolic hepatitis, or non-alcoholic fatty liver disease; (2) Concurrent infections with other viruses causing liver injury, such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), or human immunodeficiency virus (HIV); (3) Presence of cirrhosis at the time of HBsAg seroclearance (defined as a Fibrosis Index Based on 4 factors [FIB-4] score \u0026ge; 3.25); (4) Diagnosis of malignancies at enrollment.\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Beijing Ditan Hospital, Capital Medical University (Approval No.: Jing Di Lun Yan Zi [2023] No. (009)-01) and registered at ClinicalTrials.gov (ID: NCT04301908; registration date: 03/06/2020; https://register.clinicaltrials.gov/).\u003c/p\u003e\n\u003cp\u003eThis was a retrospective study, and the ethics committee waived the requirement for informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData were collected through the Hospital Information System (HIS) and Laboratory Information System (LIS), including patients\u0026apos;\u0026nbsp;demographic data\u0026nbsp;(age, gender),\u0026nbsp;treatment information\u0026nbsp;(antiviral treatment regimens, discontinuation time),\u0026nbsp;baseline data at Peg-IFN\u0026alpha; treatment cessation\u0026nbsp;(HBsAb levels, HBV DNA levels, liver function, imaging results, etc., at the time of HBsAg seroclearance and treatment discontinuation),\u0026nbsp;endpoint follow-up data (time and type of liver-related adverse events, or last follow-up date),\u0026nbsp;liver function parameters, HBV virological and serological indicators\u0026nbsp;assessed every 3\u0026ndash;6 months during follow-up, and\u0026nbsp;hepatic imaging results\u0026nbsp;evaluated every 6\u0026ndash;12 months.\u003c/p\u003e\n\u003cp\u003ePatients in this study were stratified according to baseline HBsAb levels into four groups: negative (\u0026lt;10 mIU/mL), low (\u0026ge;10 and \u0026lt;100 mIU/mL), medium (\u0026ge;100 and \u0026lt;1000 mIU/mL), and high (\u0026ge;1000 mIU/mL).\u003c/p\u003e\n\u003cp\u003eAdditionally, based on changes in HBsAb levels from HBsAg seroclearance (treatment discontinuation) to the end of follow-up, patients were divided into three groups: Decline group\u0026nbsp;(downgrade in HBsAb level category), Stable group\u0026nbsp;(no change in HBsAb level category), Rise group\u0026nbsp;(upgrade in HBsAb level category).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLaboratory Testing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll clinical biochemical and virological indicators were measured at the Clinical Laboratory Center of Beijing Ditan Hospital. HBsAg and HBsAb levels were determined using the Abbott microparticle chemiluminescence immunoassay (Abbott Laboratories, USA; Abbott i2000 automated immunoassay analyzer). The upper detection limits were HBsAg \u0026gt;250 IU/mL and HBsAb \u0026gt;1000 mIU/mL, with HBsAb \u0026ge;10 mIU/mL defined as HBsAb positivity. HBV DNA was quantified using fluorescent quantitative polymerase chain reaction (Roche, Switzerland; Light Cycler 480 PCR system), with a lower detection limit of 20 IU/mL. Liver function tests were performed using the Hitachi 7180 automated biochemical analyzer. Hepatocellular carcinoma (HCC) and cirrhotic ascites were assessed via color Doppler flow imaging (Siemens, USA; ACUSON X150), computed tomography (Siemens, USA; SOMATOM Definition AS), or magnetic resonance imaging (Siemens, USA; MAGNETOM Skyra).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe incidence of liver-related adverse events (cirrhotic ascites, liver failure, upper gastrointestinal bleeding, and HCC) following HBsAg clearance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData were analyzed using SPSS 19.0 and visualized with GraphPad Prism. Normally distributed continuous data are presented as mean \u0026plusmn; standard deviation and compared using ANOVA or an independent samples t-test. Non-normally distributed continuous data are expressed as median (interquartile range) and analyzed with the Mann-Whitney U test. Paired samples were compared using the paired t-test or the Wilcoxon signed-rank test for non-normal data. Categorical data are reported as frequency (percentage) and analyzed with the chi-square test. Correlation analyses included: Point-biserial correlation for binary categorical vs. non-normal continuous variables; Phi coefficient for two binary categorical variables; Spearman\u0026rsquo;s rank correlation for categorical vs. ordinal variables, two ordinal variables, or ordinal vs. continuous variables. All statistical tests were two-tailed, with significance defined as \u0026alpha; = 0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eDemographic Data of Patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 645 patients who achieved HBsAg seroclearance after Peg-IFN\u0026alpha; therapy were enrolled. Of these, 189 were excluded due to follow-up durations \u0026lt;48 weeks, 20 due to missing HBsAb results at the study endpoint, and 46 due to baseline cirrhosis. Ultimately, 390 patients were included in the analysis. The median age at the time of HBsAg seroclearance and treatment discontinuation was 38.00 (interquartile range: 32.00, 44.00) years, with a median follow-up duration of 53.50 (range: 11.00\u0026ndash;173.00 months).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline HBsAb Level Grouping Data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients were stratified into four groups based on baseline HBsAb levels: negative group (n=70), low-level group (n=112), intermediate-level group (n=165), and high-level group (n=43). The median ages at HBsAg clearance and treatment discontinuation were 42.50 (37.00, 47.00), 38.00 (33.25, 44.00), 37.00 (32.00, 42.00), and 33.00 (29.00, 40.00) years, respectively, with statistically significant differences among the groups (H = 28.519, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001). A correlation analysis between baseline HBsAb levels and age at HBsAg seroclearance revealed a weak negative correlation (rs = -0.248, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001). The correlation coefficient matrix for all variables is shown in Table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Correlation Matrix of the Variables\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"1021\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 55px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 55px;\"\u003e\n \u003cp\u003eALT abnormal \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 55px;\"\u003e\n \u003cp\u003eAST\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 55px;\"\u003e\n \u003cp\u003eTBIL\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 52px;\"\u003e\n \u003cp\u003eALB\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 52px;\"\u003e\n \u003cp\u003eHGB\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 54px;\"\u003e\n \u003cp\u003ePLT\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 73px;\"\u003e\n \u003cp\u003eALT\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 55px;\"\u003e\n \u003cp\u003eAST\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 55px;\"\u003e\n \u003cp\u003eTBIL\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 55px;\"\u003e\n \u003cp\u003eALB\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 55px;\"\u003e\n \u003cp\u003eHGB\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 55px;\"\u003e\n \u003cp\u003ePLT\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 55px;\"\u003e\n \u003cp\u003eAdverse events\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 55px;\"\u003e\n \u003cp\u003eLiver cirrhosis \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eHBsAb level classification \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.127*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eALT abnormal \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e-0.120*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eAST\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e-0.119*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.083\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.381**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eTBIL\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e-0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.075\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eALB\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.092\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eHGB\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e-0.076\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.101*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003ePLT\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.117*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.266**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e-0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.094\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eALT\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e-0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.173**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.144**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.075\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e-0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e-0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eAST\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.046\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.077\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.119*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.148**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.307**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eTBIL\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.164**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.080\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.229**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.093\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eALB\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e-0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.191**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.040\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e-0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.098\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e-0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e-0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.071\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eHGB\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e-0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.167**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.111*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.069\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.263**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.052\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.062\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003ePLT\u003c/p\u003e\n \u003cp\u003eabnormal \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.071\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.167*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.135*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.176**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.093\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.030\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.037\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eAdverse events\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e-0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e-0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e-0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e-0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.254**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eLiver cirrhosis \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.103*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.067\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.194\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.080\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.135*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.141\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.456**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.282*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eHBsAb level classification \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e-0.248**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.124*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.123*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e-0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e-0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.100*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.106*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.083\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 67px;\"\u003e\n \u003cp\u003eChanges in HBsAb stratification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e-0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e-0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e-0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.119*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.071\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.125*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-0.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e-0.454**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNote\u003c/strong\u003e: The superscript letter \u0026quot;b\u0026quot; indicates data at baseline/HBsAg clearance discontinuation, and the superscript letter \u0026quot;e\u0026quot; indicates data at the endpoint/follow-up conclusion. ALT abnormalityᵇ, AST abnormalityᵇ, TBIL abnormalityᵇ, ALB abnormalityᵇ, HGB abnormalityᵇ, and PLT abnormalityᵇ denote data at HBsAg clearance discontinuation. ALT abnormalityᵉ, AST abnormalityᵉ, TBIL abnormalityᵉ, ALB abnormalityᵉ, HGB abnormalityᵉ, and PLT abnormalityᵉ denote data at follow-up conclusion. HBsAb grading refers to categorization based on baseline HBsAb levels, while HBsAb grading change is categorized according to the shift in HBsAb levels from baseline to endpoint. P value: ** denotes significant correlation at the 0.01 level (two-sided); * indicates significant correlation at the 0.05 level (two-sided).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBaseline ALT abnormality rates showed no significant differences among the four groups [35 (50.00%) vs. 58 (51.78%) vs. 100 (60.61%) vs. 30 (69.77%), \u0026chi;\u0026sup2; = 6.379, \u003cem\u003eP\u003c/em\u003e = 0.095], whereas baseline AST abnormality rates differed significantly [9 (12.86%) vs. 17 (15.18%) vs. 31 (18.79%) vs. 14 (32.56%), \u0026chi;\u0026sup2; = 8.020, \u003cem\u003eP\u003c/em\u003e = 0.046]. Correlation analysis between baseline HBsAb levels and ALT/AST abnormality rates at HBsAg clearance cessation revealed a weak positive association (rs = 0.124, \u003cem\u003eP\u003c/em\u003e = 0.014; rs = 0.123, \u003cem\u003eP\u003c/em\u003e = 0.015). Other baseline liver function parameters\u0026mdash;TBIL, HGB, PLT, and ALB\u0026mdash;showed no significant intergroup differences (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003eThe overall follow-up duration was 53.50 (11.00\u0026ndash;173.00) months, with no significant differences among the negative, low-, moderate-, and high-level groups [50.50 (12.00\u0026ndash;173.00), 46.50 (12.00\u0026ndash;164.00), 59.00 (12.00\u0026ndash;160.00), and 60.00 (11.00\u0026ndash;118.00) months, respectively; H = 3.689, \u003cem\u003eP\u003c/em\u003e = 0.297]. Endpoint ALT, AST, TBIL, ALB, HGB, and PLT levels also showed no significant intergroup differences (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003eBy the end of follow-up, 4 patients developed hepatic adverse events (2 HCC, 2 ascites). The incidence rates were 0.00% (0/70) in the negative group, 0.89% (1/112) in the low-level group, 0.61% (1/165) in the moderate-level group, and 4.65% (2/43) in the high-level group, with no statistical significance (\u0026chi;\u0026sup2; = 4.471, \u003cem\u003eP\u003c/em\u003e = 0.143). Additionally, 3 patients developed cirrhosis, with no significant intergroup differences in incidence [0.00% (0/70) vs. 0.89% (1/112) vs. 0.61% (1/165) vs. 2.33% (2/43); \u0026chi;\u0026sup2; = 2.271, \u003cem\u003eP\u003c/em\u003e = 0.513]. Detailed patient characteristics are shown in Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Patient Characteristics by Baseline HBsAb Levels\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"667\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003eAll patients (n=390)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003eNegative group(n=70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003elow-level group (n=112)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003emoderate-level group (n=165)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003ehigh-level group (n=43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;2 / H\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003eMale (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e268(68.72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e48(68.57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e79(70.54%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e115(69.70%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e26(60.47%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e1.609\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.657\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e38.00(32.00,44.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e42.50(37.00,47.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e38.00(33.25,44.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e37.00(32.00,42.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e33.00(29.00,40.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e28.519\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003eAdverse events (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e4(1.03%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1(0.89%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1(0.61%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e2(4.65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e4.471\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.143\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003eALT abnormal \u003csup\u003eb\u003c/sup\u003e (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e223(57.18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e35(50.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e58(51.78%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e100(60.61%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e30(69.77%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e6.379\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.095\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003eAST abnormal \u003csup\u003eb\u003c/sup\u003e (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e71(18.21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e9(12.86%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e17(15.18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e31(18.79%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e14(32.56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e8.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.046\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003eTBIL abnormal \u003csup\u003eb\u003c/sup\u003e (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e23(5.90%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e5(7.14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e5(4.46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e12(7.27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1(2.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e1.881\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.576\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003eALB abnormal \u003csup\u003eb\u003c/sup\u003e (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e8(2.05%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e2(2.86%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e3(2.68%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e2(1.21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1(2.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e1.645\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.680\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003eHGB abnormal \u003csup\u003eb\u003c/sup\u003e (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e48(12.31%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e9(12.86%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e16(14.29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e19(11.52%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e4(9.30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e0.881\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.830\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003ePLT abnormal \u003csup\u003eb\u003c/sup\u003e (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e103(26.41%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e16(22.86%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e27(24.11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e52(31.52%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e8(18.60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e4.321\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.230\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003eALT abnormal \u003csup\u003ee\u003c/sup\u003e (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e116(29.74%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e20(28.57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e31(27.68%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e48(29.10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e17(39.53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e2.281\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.516\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003eAST abnormal \u003csup\u003ee\u003c/sup\u003e (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e15(3.85%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e4(3.57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e8(4.85%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e3(6.98%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e4.885\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.152\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003eTBIL abnormal \u003csup\u003ee\u003c/sup\u003e (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e68(17.44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e15(21.43%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e17(15.18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e28(16.97%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e8(18.60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e1.237\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.756\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003eALB abnormal \u003csup\u003ee\u003c/sup\u003e (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e9(2.31%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e2(1.79%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e4(2.42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e3(6.98%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e4.867\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.130\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003eHGB abnormal \u003csup\u003ee\u003c/sup\u003e (n, %))\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e14(3.59%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e5(7.14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e2(1.79%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e7(4.24%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e4.644\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.157\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003ePLT abnormal \u003csup\u003ee\u003c/sup\u003e (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e14(3.59%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e2(2.86%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e4(3.57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e6(3.64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e2(4.65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e0.504\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.935\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003eLiver cirrhosis \u003csup\u003ee\u003c/sup\u003e (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e3(0.77%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1(0.89%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1(0.61%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1(2.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 42px;\"\u003e\n \u003cp\u003e2.271\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.513\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05 indicates a statistically significant difference. Groups were defined as follows: Negative group (HBsAb \u0026lt;10 mIU/mL), low-level group (HBsAb \u0026ge;10 mIU/mL and \u0026lt;100 mIU/mL), moderate-level group (HBsAb \u0026ge;100 mIU/mL and \u0026lt;1000 mIU/mL), and high-level group (HBsAb \u0026ge;1000 mIU/mL).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eChanges in HBsAb During Follow-up and the Occurrence of Adverse Events\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBased on changes in HBsAb levels during the follow-up period, the study population was divided into three groups: a decline group (131 cases), a stable group (154 cases), and an increase group (105 cases). The incidence of liver-related adverse events during follow-up in the HBsAb decline, stable, and increase groups was 3.05% (4/131), 0.00% (0/154), and 0.00% (0/105), respectively, showing a statistically significant difference (\u0026chi;\u0026sup2; = 5.694, \u003cem\u003eP\u003c/em\u003e = 0.017). Correlation analysis between HBsAb level changes and liver-related adverse event incidence revealed a weak but statistically significant negative correlation (rs = -0.125, \u003cem\u003eP\u003c/em\u003e = 0.014).\u003c/p\u003e\n\u003cp\u003eAt the end of follow-up, a total of 3 patients developed liver cirrhosis, with no significant differences observed among the HBsAb decline, stable, and increase groups [1.53% (2/131) vs. 0.00% (0/154) vs. 0.95% (1/105); \u0026chi;\u0026sup2; = 2.266, \u003cem\u003eP\u003c/em\u003e = 0.367]. Additionally, baseline and endpoint liver function indicators (ALT, AST, TBIL, ALB), hemoglobin (HGB) levels, and platelet (PLT) counts showed no significant differences among the three groups. Detailed patient characteristics are presented in Figure 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbnormal Transaminase Levels During Follow-up and the Development of Liver Cirrhosis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNeither baseline HBsAb levels nor changes in HBsAb levels during follow-up had a significant impact on the development of liver cirrhosis. By the end of follow-up, only 3 patients had progressed to cirrhosis. Therefore, we further investigated the association between transaminase levels and cirrhosis development.\u003c/p\u003e\n\u003cp\u003eThe incidence of endpoint cirrhosis showed no significant difference between patients with normal and abnormal baseline ALT levels [1.98% (2/167) vs. 0.45% (1/223), Fisher\u0026apos;s exact test, \u003cem\u003eP\u003c/em\u003e = 0.579] or between those with normal and abnormal baseline AST levels [0.63% (2/319) vs. 1.41% (1/71), Fisher\u0026apos;s exact test, \u003cem\u003eP\u003c/em\u003e = 0.454]. However, a significant difference was observed in endpoint cirrhosis incidence between patients with normal and abnormal endpoint ALT levels [0.00% (0/274) vs. 2.59% (3/116), Fisher\u0026apos;s exact test, \u003cem\u003eP\u003c/em\u003e = 0.026], though no such difference existed for endpoint AST levels [0.80% (3/375) vs. 0% (0/15), Fisher, \u003cem\u003eP\u003c/em\u003e \u0026gt; 0.999]. Analysis of the correlation between endpoint cirrhosis incidence and endpoint ALT abnormality rates revealed a weak positive association (rs = 0.135, P = 0.026).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eGlobally, over 325 million people are chronically infected with hepatitis B virus (HBV). Despite the availability of effective vaccines, nearly 1 million individuals die annually from HBV-related complications\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e8\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. Chronic HBV infection significantly increases the risk of developing advanced liver diseases, and hepatocellular carcinoma (HCC) is closely associated with HBV infection. It is estimated that approximately 830,000 people worldwide die from liver cancer annually, with 906,000 new cases reported each year\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e9\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. In the Asia-Pacific region, primary liver cancer has the highest incidence rate, ranking as the second leading cause of cancer-related death and the fifth most prevalent cancer type\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e9\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIn patients with chronic HBV infection, long-term antiviral therapy with nucleos(t)ide analogues (NAs) can effectively suppress HBV DNA replication, reverse liver fibrosis and cirrhosis, and reduce the incidence of liver-related adverse events such as HCC and cirrhosis complications. However, the serological clearance of hepatitis B surface antigen (HBsAg) remains rare\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e10\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e11\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. HBsAg clearance reduces the risk of hepatic decompensation and HCC. Pegylated interferon-alpha (Peg-IFN\u0026alpha;) treatment has been shown to enhance HBsAg seroconversion rates by modulating immune responses, including HBV-specific B lymphocytes and cytotoxic T lymphocytes (CTLs)\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e12\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eCD8-positive T lymphocytes (CD8+ T cells) are critical for controlling HBV infection in the liver by eliminating infected hepatocytes\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e13\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. Single-cell sequencing of peripheral blood has revealed that HBV polymerase 455 (HBV pol455)-specific CD8+ T cells with cytotoxic features\u0026mdash;characterized by high expression of granulysin (GNLY), granzyme B (GZMB), perforin 1 (PRF1), and natural killer cell granule protein 7 (NKG7)\u0026mdash;are associated with intrinsic HBV control[\u003csup\u003e14\u003c/sup\u003e]. During chronic infection, virus-specific CD8+ T cells often become dysfunctional and fail to clear infected hepatocytes\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e15\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e16\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e17\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e.In patients achieving HBsAg clearance, single-cell sequencing of liver samples demonstrates a significant reduction in exhausted CD8+ T cells expressing programmed death-1 (PD1+), T-cell immunoglobulin and mucin-domain containing-3 (TIM3+), and lymphocyte-activation gene-3 (LAG3+)\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e18\u003c/sup\u003e\u003csup\u003e]\u0026nbsp;\u003c/sup\u003e. These findings suggest that although CD8+ T cells may become functionally exhausted during chronic infection, their activity can be restored upon HBsAg clearance, highlighting their pivotal role in antiviral immunity.\u003c/p\u003e\n\u003cp\u003eB lymphocytes play a key role in initiating antiviral immune responses following HBV exposure. Early-activated B cells exhibit upregulated expression of major histocompatibility complex class II (MHC-II), C-X-C motif chemokine receptor 5 (CXCR5), and PD-1, which are closely associated with B cell activation and immune regulation. Peg-IFN\u0026alpha; therapy induces an increase in B cell levels, particularly plasmablasts (CD19+CD38+), which inversely correlate with hepatitis B antigen levels\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e19\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. HBV recovery typically involves two seroconversion events: HBsAg loss accompanied by HBsAb emergence, and HBeAg loss with HBeAb seroconversion. B cells are believed to play a central role in this process\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e19\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e.Activated B cells rapidly produce specific antibodies, providing robust immune protection\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e20\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e21\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. HBsAb facilitates the clearance of HBV-infected cells through antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP)\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e22\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e23\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. Thus, HBsAb positivity typically indicates HBV recovery and HBsAg clearance. However, the relationship between HBsAb and post-treatment liver-related adverse events following HBsAg seroconversion remains unclear. The inhibitory effect of HBsAb on HBV infection is illustrated in Figure 2.\u003c/p\u003e\n\u003cp\u003eIn this study, the age at HBsAg seroclearance and treatment discontinuation differed significantly among groups with varying HBsAb levels, indicating that higher HBsAb levels were associated with younger ages at treatment discontinuation. HBsAb is secreted by HBV-specific B cells, and its level is closely related to the functional activity of B-cell immunity. During HBV infection, the generation and function of antigen-specific memory B cells are critical for pathogen clearance and long-term immune control\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e24\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. However, B-cell production capacity gradually declines with age, resulting in weakened immune function\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e24\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. This age-related immune decline may explain the negative correlation between HBsAb levels and discontinuation age (rs = -0.248, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003eHBsAb levels are closely linked to immune activity. Active immune attacks on residual viruses or infected hepatocytes may cause hepatocellular damage, elevating AST and ALT levels\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e25\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e26\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. Studies indicate that during peg-IFN\u0026alpha; therapy for CHB, elevated transaminase levels are significantly associated with higher HBsAg clearance rates\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e27\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e28\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. Our study found significant differences in abnormal ALT and AST rates among HBsAb-level groups, with higher HBsAb levels associated with increased ALT and AST abnormalities (rs = 0.124, \u003cem\u003eP\u003c/em\u003e = 0.014; rs = 0.123, \u003cem\u003eP\u003c/em\u003e = 0.015). ALT and AST are key markers for liver function assessment, and ALT is generally considered more directly linked to hepatic activity\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e29\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. The observed association between high HBsAb levels and elevated AST in this study may suggest stronger immune activation in patients receiving peg-IFN\u0026alpha; therapy.\u003c/p\u003e\n\u003cp\u003eIn this study, although the occurrence of liver-related adverse events was not associated with baseline HBsAb levels, a significant negative correlation was observed with dynamic changes in HBsAb levels during follow-up (rs = -0.125, P = 0.014). Notably, a decline in HBsAb level category corresponded to an increased incidence of hepatic adverse events. Among the cohort, four HBsAg-serocleared patients who discontinued treatment experienced liver-related adverse events during follow-up, all occurring in the HBsAb-declining subgroup.\u003c/p\u003e\n\u003cp\u003eHBsAb-specific B cells have been identified as valuable predictive biomarkers for HBsAg seroconversion in treatment-na\u0026iuml;ve chronic HBV-infected patients\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e30\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. For those who achieved HBsAg clearance, previous studies demonstrated that HBsAb levels influence the durability of peg-IFN\u0026alpha;-induced HBsAg loss\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e7\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e31\u003c/sup\u003e\u003csup\u003e,\u0026nbsp;\u003c/sup\u003e\u003csup\u003e32\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. However, regarding hepatic adverse events, existing research indicates that serological conversion status does not affect the risk of such events\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e33\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e, consistent with our findings that post-HBsAg clearance, HBsAb levels lack direct correlation with adverse event occurrence. Although baseline antibody levels may partially predict post-HBsAg-clearance relapse, they likely fail to comprehensively reflect dynamic immune system changes or complex virus-host interactions. In contrast, longitudinal HBsAb level alterations directly mirror immune response activity. Our data revealed a significant negative correlation between declining HBsAb levels and liver adverse events, with all four adverse event cases clustered in the HBsAb-declining subgroup. These findings suggest that waning HBsAb levels may weaken immune protection, potentially increasing the risk of viral reactivation or hepatocellular injury.\u003c/p\u003e\n\u003cp\u003eALT, a sensitive marker of hepatocellular damage, reflects persistent hepatic inflammation and cellular injury\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e29\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. At the follow-up endpoint, three cirrhosis cases were identified, all occurring in patients with abnormal ALT levels. A positive correlation was observed between the incidence of cirrhosis and the rate of endpoint ALT abnormalities, with cirrhosis prevalence increasing alongside ALT abnormality (rs = 0.135, P = 0.026). Persistent ALT abnormalities indicate ongoing chronic liver injury, potentially driven by repeated hepatocyte necrosis, hyperactivation of hepatic stellate cells, and aberrant extracellular matrix deposition\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e34\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. This chronic inflammatory microenvironment promotes fibrogenesis, ultimately leading to cirrhosis\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e35\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. These findings highlight the importance of closely monitoring ALT abnormalities in HBsAg-serocleared patients to implement timely interventions that may decelerate cirrhotic progression and improve long-term outcomes.\u003c/p\u003e\n\u003cp\u003eThis study has several limitations, including a relatively small sample size and low incidence of hepatic adverse events, potentially affecting statistical power. Other confounding factors (host genetics, viral genotypes, family history) were not systematically analyzed. Furthermore, non-invasive biomarkers rather than liver biopsy (the diagnostic gold standard) were used for cirrhosis evaluation, introducing potential diagnostic inaccuracies. Future multicenter, large-scale, gold standard-based prospective studies are warranted.\u003c/p\u003e\n\u003cp\u003eIn HBsAg-serocleared, non-cirrhotic patients after treatment cessation, longitudinal HBsAb decline, rather than baseline HBsAb levels, may indicate increased risk of hepatic adverse events. This emphasizes the clinical importance of dynamic HBsAb monitoring to optimize long-term prognosis assessment and management strategies.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eDeclining HBsAb levels after HBsAg clearance may be associated with an increased risk of hepatic adverse events.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eHBsAb\u003c/p\u003e\n\u003cp\u003eHepatitis B surface antibody\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHBsAg\u003c/p\u003e\n\u003cp\u003eHepatitis B surface antigen\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePeg-IFN\u0026alpha;\u003c/p\u003e\n\u003cp\u003ePegylated interferon-alpha\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHBV\u003c/p\u003e\n\u003cp\u003eHepatitis B virus\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHCC\u003c/p\u003e\n\u003cp\u003eHepatocellular carcinoma\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHBeAg\u003c/p\u003e\n\u003cp\u003eHepatitis B e antigen\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHIS\u003c/p\u003e\n\u003cp\u003eHospital Information System\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLIS\u003c/p\u003e\n\u003cp\u003eLaboratory Information System\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eALT\u003c/p\u003e\n\u003cp\u003eAlanine Aminotransferase\u003c/p\u003e\n\u003cp\u003eAST\u003c/p\u003e\n\u003cp\u003eAspartate Aminotransferase\u003c/p\u003e\n\u003cp\u003eTBIL\u003c/p\u003e\n\u003cp\u003eTotal Bilirubin\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eALB\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlbumin\u003c/p\u003e\n\u003cp\u003eHGB\u003c/p\u003e\n\u003cp\u003eHemoglobin\u003c/p\u003e\n\u003cp\u003ePLT\u003c/p\u003e\n\u003cp\u003ePlatelet Count\u003c/p\u003e\n\u003cp\u003eNAs\u003c/p\u003e\n\u003cp\u003eNucleos(t)ide analogues\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCTLs\u003c/p\u003e\n\u003cp\u003eCytotoxic T lymphocytes\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCD8+ T cells\u003c/p\u003e\n\u003cp\u003eCD8-positive T lymphocytes\u003c/p\u003e\n\u003cp\u003eHBV pol455\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHBV polymerase 455\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGNLY\u003c/p\u003e\n\u003cp\u003eGranulysin\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGZMB\u003c/p\u003e\n\u003cp\u003eGranzyme B\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePRF1\u003c/p\u003e\n\u003cp\u003ePerforin 1\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNKG7\u003c/p\u003e\n\u003cp\u003eNatural killer cell granule protein 7\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePD1+\u003c/p\u003e\n\u003cp\u003eProgrammed death-1\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTIM3+\u003c/p\u003e\n\u003cp\u003eT-cell immunoglobulin and mucin-domain containing-3\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLAG3+\u003c/p\u003e\n\u003cp\u003eLymphocyte-activation gene-3\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMHC-II\u003c/p\u003e\n\u003cp\u003eMajor histocompatibility complex class II\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCXCR5\u003c/p\u003e\n\u003cp\u003eC-X-C motif chemokine receptor 5\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eADCC\u003c/p\u003e\n\u003cp\u003eAntibody-dependent cell-mediated cytotoxicity\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eADCP\u003c/p\u003e\n\u003cp\u003eAntibody-dependent cellular phagocytosis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNTCP\u003c/p\u003e\n\u003cp\u003eSodium Taurocholate Cotransporting Polypeptide\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Beijing Ditan Hospital, Capital Medical University (Approval No.: Jing Di Lun Yan Zi [2023] No. (009)-01).\u0026nbsp;Written informed consent for participation was not required for this study under the national legislation and institutional requirements.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was registered at ClinicalTrials.gov (ID: NCT04301908; registration date: 03/06/2020; https://register.clinicaltrials.gov/).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis manuscript is approved by all authors for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data are included in the original manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Capital Health Development and Scientific Research of\u0026nbsp;special public health project (BRWEP2024W102170101).The National Key Research and Development Program (2022YFC2603500, 2022YFC2603505,2023YFC2306901,2023YFC2308105); The capital health\u0026nbsp;research and development of special public health project (2022-1-2172); Beijing Municipal Health Commission high-level public health technical personnel construction project(discipline leader -03-26, discipline backbone-02-28); Beijing Hospitals Authority \u0026quot;peak\u0026quot; talent training program(DFL20241803);\u0026nbsp;Beijing Hospitals Authority Clinical medicine Development of special funding support (ZLRK202301).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDW drafted the manuscript. DW, CXX, ZZY and LXX performed the data analysis and revised the manuscript. CWH, ZYQ, WSY, YLM, WX, WSJ, GZX collected the clinical information. XY and LMH conceptualized and designed the study, interpreted the results, and critically reviewed and revised the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research was funded by the fundings: Beijing Research Ward Excellence Program (BRWEP2024W102170101). The National Key Research and Development Program (2022YFC2603500, 2022YFC2603505,2023YFC2306901,2023YFC2308105); The capital health research and development of special public health project (2022-1-2172); Beijing Municipal Health Commission high-level public health technical personnel construction project(discipline leader -03-26, discipline backbone-02-28); Beijing Hospitals Authority \u0026quot;peak\u0026quot; talent training program(DFL20241803); Beijing Hospitals Authority Clinical medicine Development of special funding support (ZLRK202301).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eYou H, Wang F, Li T, et al. Guidelines for the prevention and treatment of chronic hepatitis B: 2022 update. J Pract Hepatol. 2023;26(3):457\u0026ndash;478. doi: 10.3760.\u003c/li\u003e\n\u003cli\u003eKanda T, Sasaki-Tanaka R, Tsuchiya A, et al. Hepatitis B virus infection and its treatment in Eastern Ethiopia. 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HBsAg Seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma. Gastroenterology. 2008;135(4):1192-1199. doi:10.1053/j.gastro.2008.07.008. \u003c/li\u003e\n\u003cli\u003eTrautwein C, Friedman SL, Schuppan D, et al. Hepatic fibrosis: Concept to treatment. J Hepatol. 2015;62(1 Suppl):S15-S24. doi:10.1016/j.jhep.2015.02.039. \u003c/li\u003e\n\u003cli\u003eMart\u0026iacute;nez Garc\u0026iacute;a de la Torre RA, Vallverd\u0026uacute; J, Xu Z, et al. Trajectory analysis of hepatic stellate cell differentiation reveals metabolic regulation of cell commitment and fibrosis. Nat Commun. 2025;16(1):1489. doi:10.1038/s41467-025-56024-4.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Chronic Hepatitis B, Hepatitis B Surface Antigen (HBsAg), Hepatitis B Surface Antibody (HBsAb), Pegylated Interferon-alpha (PEG-IFNα) ","lastPublishedDoi":"10.21203/rs.3.rs-7111922/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7111922/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe relationship between changes in hepatitis B surface antibody (HBsAb) levels and hepatic adverse events after hepatitis B surface antigen (HBsAg) clearance remains unclear. This study aimed to investigate the correlation between HBsAb level changes and hepatic adverse events in non-cirrhotic patients following HBsAg clearance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe retrospectively analyzed patients with HBsAg seroclearance achieved via pegylated interferon-alpha (Peg-IFNα) therapy in the Department of Hepatology II at Beijing Ditan Hospital, Capital Medical University, from October 2008 to December 2023. Participants were stratified by baseline HBsAb levels into negative (\u0026lt;10 mIU/mL), low (10–100 mIU/mL), medium (100–1000 mIU/mL), and high (≥1000 mIU/mL) groups. Based on HBsAb trends during follow-up, patients were categorized into declining, stable, and rising groups. The primary endpoint was the incidence of hepatic adverse events after HBsAg clearance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 390 patients were included, with a median age of 38.00 (32.00–44.00) years and median follow-up of 53.50 (11.00–173.00) months. During follow-up, 4 cases of hepatic adverse events occurred, all in the declining group (4 cases, 3.05%), while none were observed in the stable or rising groups (\u003cem\u003eP\u003c/em\u003e = 0.017). Changes in HBsAb levels were inversely correlated with the incidence of hepatic adverse events (\u003cem\u003ers\u003c/em\u003e = -0.125, \u003cem\u003eP\u003c/em\u003e = 0.014).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDeclining HBsAb levels after HBsAg clearance may be associated with an increased risk of hepatic adverse events.\u003c/p\u003e","manuscriptTitle":"Association Between Changes in HBsAb Levels and Hepatic Adverse Events After HBsAg Clearance in Non-Cirrhotic Chronic Hepatitis B Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-21 16:08:12","doi":"10.21203/rs.3.rs-7111922/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-12T08:52:31+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-08T15:51:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T13:42:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"95913774083310200740400401188925673154","date":"2026-05-01T13:34:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"140923484184499852283535675160148836648","date":"2026-04-30T16:28:34+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-17T14:19:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"70011041439881623940397509555555404545","date":"2025-09-05T08:48:32+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-13T12:23:37+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-18T09:32:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-17T07:37:37+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-17T07:36:27+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2025-07-13T07:47:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0f6dc780-bc8e-47fe-bc2e-b51bbe2e194e","owner":[],"postedDate":"August 21st, 2025","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-12T08:52:31+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-08T15:51:49+00:00","index":194,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T13:42:25+00:00","index":193,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-25T02:38:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-21 16:08:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7111922","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7111922","identity":"rs-7111922","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}