Impact of Metabolic Associated Steatotic Liver Disease on Antiviral Therapy Outcomes in Chronic Hepatitis B Patients: Insights from Real-World and Clinical Cohorts

Impact of Metabolic Associated Steatotic Liver Disease on Antiviral Therapy Outcomes in Chronic Hepatitis B Patients: Insights from Real-World and Clinical Cohorts | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL Journal of Medical Virology This is a preprint and has not been peer reviewed. Data may be preliminary. 6 October 2025 V1 Latest version Share on Impact of Metabolic Associated Steatotic Liver Disease on Antiviral Therapy Outcomes in Chronic Hepatitis B Patients: Insights from Real-World and Clinical Cohorts Authors : Sheng-Jie Shiue , Dr. Chao-Ling Cheng , Sheng-Wei Cheng , Dr. Chun‐Nan Chen , Shih-Ping Huang , Yan Kang Lee , Li-Wei Wu , … Show All … , Han-Shiang Shiue , Tze-Sian Chan , Hsin-Yi Lin , Dr. Hsien-Yao Yang , Kuo-Feng Leng , and Dr. Ming Shun Wu 0000-0002-5755-9062 [email protected] Show Fewer Authors Info & Affiliations https://doi.org/10.22541/au.175975410.08190287/v1 248 views 116 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background and Aim, Chronic hepatitis B (CHB) affects over 250 million people globally and is a major contributor to liver complications, including cirrhosis and hepatocellular carcinoma (HCC). Though antiviral therapies suppress HBV, the rising prevalence of metabolic-associated steatotic liver disease (MASLD) poses new challenges. This study assessed how MASLD influences liver-related outcomes, fibrosis progression, and survival in CHB patients undergoing Neucleos(t)ide analogues (NA) therapy, using real-world data and clinical cohort analysis. Methods, A retrospective study using the TriNetX US Collaborative Network, CHB patients receiving long-term NA therapy with undetectable serum HBV DNA and concomitant MASLD (CHB-MASLD-NA) were compared with those without MASLD (CHB-non MASLD-NA), matched 1:1 by propensity scores (n=4,761 each). Primary outcomes included 10-year incidence of HCC and cirrhosis, with survival assessed via Kaplan-Meier curves and hazard ratios (HRs) from Cox models. Separately, a clinical cohort of 64 CHB patients and 137 MASLD-only patients was assessed for steatosis (controlled attenuation parameter, CAP) and fibrosis (liver stiffness). Results, CHB-MASLD-NA patients had higher risks of cirrhosis/HCC (HR 1.747, 95% CI 1.526–2.001; RR 1.965, 95% CI 1.733–2.228; p<0.001) and lower 10-year survival (61.45% vs. 79.30%, p<0.001). In the clinical cohort, CHB-MASLD-NA patients showed greater liver stiffness (9.853 kPa vs. 4.952 kPa) and higher advanced fibrosis rates (28.0%) than CHB alone-NA (14.3%) and MASLD-non CHB (4.38%) groups. Conclusions, MASLD drives liver fibrosis, worsening liver outcomes and survival in CHB patients under effective NA therapy, highlighting the need for dual targeting of HBV suppression and metabolic dysfunction. Impact of Metabolic Associated Steatotic Liver Disease on Antiviral Therapy Outcomes in Chronic Hepatitis B Patients: Insights from Real-World and Clinical Cohorts Shih-Ping Huang a,1 , Sheng-Jie Shiue a,1 , Hsin-Yi Lin b,c,1 , Sheng-Wei Cheng d , Li-Wei Wu e , Tze-Sian Chan a,f , Chun-Nan Chen a , Chao-Ling Cheng a,f , Yan Kang Lee a , Hsien-Yao Yang a , Han-Shiang Shiue a,g , Kuo-Feng Leng a , Ming-Shun Wu a,f,h,* a Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan. b Graduate Institute of Chemical Engineering, National Taipei University of Technology, Taipei 106, Taiwan c Graduate Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei, Taiwan d Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taiwan Adventist Hospital, Taipei 105, Taiwan. e Department of Internal Medicine, National Taiwan University Cancer center, Taipei,106 Taiwan. f Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. g International Ph.D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei, 106, Taiwan. h TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, 110, Taiwan. 1. Shih-Ping Huang, Sheng-Jie Shiue and Hsin-Yi Lin contributed equally to this work. 2. *Correspondence. Short Title: Impacts of MASLD on the Outcomes of Antiviral Therapy in CHB Patients Corresponding Author: Ming-Shun Wu E-mail address: [email protected] Abstract Background and Aim, Chronic hepatitis B (CHB) affects over 250 million people globally and is a major contributor to liver complications, including cirrhosis and hepatocellular carcinoma (HCC). Though antiviral therapies suppress HBV, the rising prevalence of metabolic-associated steatotic liver disease (MASLD) poses new challenges. This study assessed how MASLD influences liver-related outcomes, fibrosis progression, and survival in CHB patients undergoing Neucleos(t)ide analogues (NA) therapy, using real-world data and clinical cohort analysis. Methods, A retrospective study using the TriNetX US Collaborative Network, CHB patients receiving long-term NA therapy with undetectable serum HBV DNA and concomitant MASLD (CHB-MASLD-NA) were compared with those without MASLD (CHB-non MASLD-NA), matched 1:1 by propensity scores (n=4,761 each). Primary outcomes included 10-year incidence of HCC and cirrhosis, with survival assessed via Kaplan-Meier curves and hazard ratios (HRs) from Cox models. Separately, a clinical cohort of 64 CHB patients and 137 MASLD-only patients was assessed for steatosis (controlled attenuation parameter, CAP) and fibrosis (liver stiffness). Results, CHB-MASLD-NA patients had higher risks of cirrhosis/HCC (HR 1.747, 95% CI 1.526–2.001; RR 1.965, 95% CI 1.733–2.228; p<0.001) and lower 10-year survival (61.45% vs. 79.30%, p<0.001). In the clinical cohort, CHB-MASLD-NA patients showed greater liver stiffness (9.853 kPa vs. 4.952 kPa) and higher advanced fibrosis rates (28.0%) than CHB alone-NA (14.3%) and MASLD-non CHB (4.38%) groups. Conclusions, MASLD drives liver fibrosis, worsening liver outcomes and survival in CHB patients under effective NA therapy, highlighting the need for dual targeting of HBV suppression and metabolic dysfunction. Key words: Chronic hepatitis B, MASLD, nucleos(t)ide analogs, cirrhosis, hepatocellular carcinoma, fibrosis, TriNetX Introduction Chronic hepatitis B (CHB) remains a formidable global health challenge, affecting over 250 million individuals and contributing to approximately 800,000 deaths annually due to cirrhosis and hepatocellular carcinoma (HCC) [1]. The advent of nucleos(t)ide analogs (NA), such as entecavir, tenofovir alafenamide, and tenofovir disoproxil, has revolutionized CHB management by effectively suppressing viral replication, reducing liver inflammation, and slowing disease progression [2]. Despite these advances, a significant proportion of CHB patients still progress to severe liver complications, highlighting the need to identify and address additional risk factors that may undermine therapeutic efficacy. In recent years, the rising global prevalence of metabolic-associated steatotic liver disease (MASLD)—previously known as nonalcoholic fatty liver disease (NAFLD)—has emerged as a critical concern in the context of CHB [3]. MASLD, characterized by hepatic steatosis in the absence of significant alcohol consumption, is closely linked to metabolic syndrome components such as obesity, type 2 diabetes, hypertension, and dyslipidemia [4]. These metabolic abnormalities drive liver inflammation and fibrosis, creating a synergistic effect when combined with chronic viral hepatitis [5]. Emerging evidence suggests that MASLD not only exacerbates liver damage in CHB patients but may also attenuate the effectiveness of NA therapies, which primarily target viral replication rather than metabolic pathways [6]. The interaction between MASLD and CHB is complex and multifaceted. Several studies have reported an increased risk of HCC in CHB patients with concurrent MASLD, even when viral replication is suppressed, likely due to metabolic-driven hepatocarcinogenesis [7]. Additionally, metabolic risk factors such as diabetes have been shown to amplify HCC risk in this population [8]. However, conflicting data exist, with some studies suggesting that hepatic steatosis might reduce HBV replication and disease severity, potentially offering a protective effect in certain contexts [9]. These discrepancies underscore the urgent need for comprehensive research to clarify the combined impact of MASLD and CHB on treatment outcomes. To address this gap, our study integrates two complementary approaches: a large-scale real-world analysis using the TriNetX US Collaborative Network and a detailed clinical cohort study. The TriNetX analysis provides robust, population-level insights into the long-term outcomes of CHB patients on NA therapy, comparing those with and without MASLD. In parallel, the clinical cohort offers granular data on hepatic steatosis and fibrosis, measured through controlled attenuation parameter (CAP) and liver stiffness, respectively, in a well-characterized group of CHB and MASLD patients. We also employ tools such as the albumin-bilirubin (ALBI) grade and fibrosis-4 (FIB-4) index to assess liver function and fibrosis severity, providing a multidimensional view of disease progression [10]. By examining liver-related complications, survival rates, and fibrosis burden, this study aims to elucidate the detrimental effects of MASLD on NA therapy outcomes in CHB patients and advocate for integrated management strategies that address both viral and metabolic drivers of liver disease. Methods Study Design This study integrated a retrospective analysis using the TriNetX US Collaborative Network, covering 68 healthcare organizations, with a clinical cohort study to evaluate MASLD’s effect on CHB patients receiving long-term NA therapy with undetectable serum HBV DNA. TriNetX Cohort CHB patients receiving long-term NA therapy with undetectable serum HBV DNA were divided into CHB-MASLD-NA (CHB with MASLD) and CHB-non MASLD-NA (CHB without MASLD) groups. MASLD was defined using ICD-10 codes for fatty liver (K76.0) or nonalcoholic steatohepatitis (K75.81) plus metabolic comorbidities (e.g., obesity [E66], type 2 diabetes [E11], hypertension [I10], dyslipidemia [E78.5]). CHB was identified via ICD-10 code B18.1. Propensity score matching (1:1) balanced cohorts for age, sex, ethnicity, ALBI/FIB-4 parameters, and comorbidities. Clinical Cohort A clinical cohort included 64 CHB patients on long-term NA therapy with undetectable serum HBV DNA, stratified by CAP into four groups: S1 (215–252, n=13), S2 (252–296, n=17), S3 (>296, n=20) and CHB patient without MASLD (CHB alone, n=14). A comparison group of 137 MASLD patients without HBV, also stratified by CAP (MASLD-non CHB, S1: n=13, S2: n=27, S3: n=97), was included. Liver stiffness was measured via transient elastography, and fibrosis stages (F0–F4) were compared across MASLD-non CHB, CHB alone-NA and CHB-MASLD-NA groups. Metabolic parameters (BMI, triglycerides, uric acid, HbA1c) and HBsAg levels were assessed. The study protocol was approved by the Institutional Review Board of Taipei Medical University (approval numbers: N201608026, N201605071, and N201805009), with informed consent obtained from all participants in accordance with the Declaration of Helsinki. The study was also registered on ClinicalTrials.gov (NCT02953600, NCT02875392, and NCT04715776). Outcome Measures TriNetX: Primary outcomes were HCC (ICD-10: C22.0) and cirrhosis (ICD-10: K74) incidence over 10 years, with survival probability as a secondary outcome. Clinical Cohort: Outcomes included liver stiffness, fibrosis stage distribution, and metabolic trends across CAP groups. Statistical Analysis TriNetX: Kaplan-Meier analysis estimated survival, with Cox models calculating hazard ratios (HRs) for liver complications, adjusting for cohort, sex, age, and HBV DNA. Risk ratios (RR), odds ratios (OR), and risk differences evaluated outcome incidence (p<0.05). Clinical Cohort: Descriptive statistics summarized liver stiffness, fibrosis stages, and metabolic parameters. Comparative analyses assessed trends across CAP groups and disease categories. Analyses were conducted on April 4, 2025, using TriNetX tools and local statistical software. Results TriNetX Cohort: Baseline Characteristics Before matching, the CHB-MASLD-NA cohort had 5,600 patients and the CHB alone-NA cohort had 11,021. After 1:1 matching, each cohort comprised 4,761 patients, balanced for age, sex, and liver function, but CHB-MASLD-NA showed higher obesity (11.4% vs. 1.9%, p<0.001) and HbA1c (6.4% vs. 5.7%, p=0.026) (Table 1). Survival and Risk Analysis for TriNetX cohort Kaplan-Meier analysis revealed a lower 10-year survival probability in CHB-MASLD-NA (61.45%) vs. CHB alone-NA (79.30%, log-rank χ² = 66.911, p<0.001). Cox models showed a 74.7% higher risk of liver complications in CHB-MASLD-NA (HR 1.747, 95% CI 1.526–2.001, p<0.001) (Table 2). HCC or cirrhosis incidence was 19.7% (519/2,632) in CHB-MASLD-NA vs. 10.0% (351/3,497) in CHB alone-NA, with a risk ratio of 1.965 (95% CI 1.733–2.228, p<0.001). The hazard ratio (HR) for adverse liver outcomes in the CHB-MASLD-NA cohort was 1.747 (95% CI 1.526–2.001, p<0.001), indicating a 74.7% increased risk compared to the CHB alone-NA cohort. This highlights the detrimental impact of MASLD on long-term survival outcomes in CHB patients receiving nucleos(t)ide analog therapy (shown in Figure 1). Cox Proportional Hazards Model The Cox proportional hazards model, conducted via the TriNetX platform (April 4, 2025, 02:18:04 UTC), analyzed data from 5,664 patients in the CHB-MASLD-NA cohort and 11,205 patients in the CHB alone-NA cohort, adjusting for key covariates. The analysis identified several significant predictors of adverse liver outcomes, including MASLD, gender, age and HBV DNA Viral Load. Notably, HBV DNA viral load under NA control was not a significant predictor of liver-related outcomes (HR 1.000, 95% CI 1.000–1.000, p=0.590), suggesting that metabolic and demographic factors may play a more dominant role in this population. (Table 2 provides a detailed breakdown of the hazard ratios and confidence intervals for each covariate.) Clinical Cohort: Fibrosis and Steatosis Patterns The clinical cohort of 64 CHB patients on NA therapy with undetectable serum HBV DNA, liver stiffness increased with steatosis (CAP), from 7.931 kPa (S1: CAP 215–252) to 9.853 kPa (S2: CAP 252–296), then slightly decreased to 9.150 kPa (S3: CAP >296) (Table 3). Metabolic markers rose with CAP: BMI from 25.240 to 29.148 kg/m², triglycerides (TG) from 113.778 to 126.286 mg/dL, HbA1c from 5.072 to 6.231, and uric acid (UA) from 5.577 to 6.360 mg/dL. HBsAg levels decreased from 2.722 to 2.539 log IU/mL. In the MASLD-non CHB group (n=137), liver stiffness was lower: 5.262 kPa (S1), 4.952 kPa (S2), and 6.228 kPa (S3), despite similar CAP levels. Fibrosis distribution showed CHB-MASLD-NA patients had the highest advanced fibrosis rate (28.0% at F4), compared to 14.3% for CHB alone-NA and 4.38% for MASLD-non CHB (shown in Figure 2). Discussion This study provides compelling evidence that MASLD significantly aggravates the prognosis of CHB patients receiving long-term NA therapy with undetectable serum HBV DNA, supported by evidence from both a large real-world dataset and a well-characterized clinical cohort. The TriNetX analysis revealed a stark 74.7% increased risk of liver-related complications, including cirrhosis and HCC, in CHB patients with MASLD (HR 1.747, 95% CI 1.526–2.001, p<0.001), alongside a 96.5% higher relative risk (RR 1.965, 95% CI 1.733–2.228, p<0.001). Survival outcomes were equally concerning, with a 10-year survival probability dropping to 61.45% in the CHB-MASLD-NA cohort compared to 79.30% in CHB alone-NA patients (p<0.001). These findings are mirrored by the clinical cohort, which demonstrated that CHB patients with MASLD exhibited significantly higher liver stiffness—peaking at 9.853 kPa in the CAP S2 group (252–296)—compared to 4.952 kPa in MASLD-non CHB patients at the same steatosis level. Furthermore, the CHB-MASLD-NA group had a 2-fold higher advanced fibrosis rate (28.0%) than CHB alone-NA patients (14.3%) and a 6-fold increase over MASLD-non CHB patients (4.38%), underscoring the synergistic burden of these conditions. The clinical cohort’s findings highlight the additive fibrogenic effect of HBV in the presence of MASLD, even when viral replication is suppressed by NA therapy. The elevated liver stiffness in CHB-MASLD-NA patients compared to MASLD-non CHB patients at matched CAP levels suggests that HBV drives additional inflammatory and fibrotic pathways, potentially through mechanisms such as oxidative stress and immune activation [11, 12]. Interestingly, HBsAg levels in the CHB-MASLD-NA group decreased with increasing CAP (from 2.722 to 2.539 log IU/mL), supporting prior observations that hepatic steatosis may suppress HBV replication [13]. However, this reduction did not translate into improved outcomes, as fibrosis progression remained pronounced, indicating that metabolic factors likely dominate disease progression in this population. This aligns with the TriNetX data, where HBV DNA viral load was not a significant predictor of adverse outcomes (HR 1.000, p=0.590), while MASLD emerged as a key independent risk factor (HR 1.547, p<0.001). The metabolic burden in CHB-MASLD-NA patients further exacerbates their risk profile. The clinical cohort showed rising trends in BMI (25.240 to 29.148 kg/m²), triglycerides (113.778 to 126.286 mg/dL), HbA1c (5.072 to 6.231), and uric acid (5.577 to 6.360 mg/dL) with increasing CAP, mirroring the TriNetX cohort’s higher obesity prevalence in CHB-MASLD-NA patients (11.4% vs. 1.9%, p<0.001) [14]. These metabolic derangements likely contribute to hepatic inflammation and fibrosis through pathways such as insulin resistance and lipid accumulation, which are well-documented drivers of hepatocarcinogenesis in MASLD [15]. The survival disparity observed in the TriNetX cohort—nearly 18% lower in CHB-MASLD-NA patients—may be amplified by these metabolic comorbidities, which compound the liver’s inflammatory milieu and accelerate disease progression. From a clinical perspective, these findings have profound implications for the management of CHB patients with MASLD. The TriNetX data’s high incidence of HCC and cirrhosis in CHB-MASLD-NA patients (19.7% vs. 10.0%) and the clinical cohort’s elevated fibrosis burden underscore the need for vigilant monitoring of liver function and fibrosis [10]. Regular screening with non-invasive tools like transient elastography, as used in our clinical cohort, can facilitate early detection of advanced fibrosis and HCC, enabling timely intervention. Moreover, the data advocate for a paradigm shift in treatment strategies. While NA therapy effectively controls viral replication, it does not address the metabolic drivers of liver disease in MASLD. Integrating antiviral therapy with targeted metabolic interventions—such as weight management, lipid-lowering therapies, and glycemic control—is critical to mitigate disease progression [16]. Lifestyle modifications, including dietary changes and increased physical activity, should be emphasized as part of patient education to enhance NA therapy efficacy and reduce complications [17]. Looking forward, our findings suggest potential avenues for therapeutic innovation. The high fibrosis burden in CHB-MASLD patients highlights the need for combination therapies that address both viral and metabolic factors. Emerging agents targeting steatosis and inflammation, such as FXR agonists or PPAR agonists, could be explored in conjunction with NAs to improve outcomes in this high-risk population [18]. Additionally, the observation that HCC can develop in MASLD patients without significant fibrosis, as noted in prior studies, calls for tailored screening approaches that account for metabolic risk factors beyond traditional fibrosis staging [19]. Future research should focus on prospective studies with larger cohorts, incorporating histologic data and detailed metabolic profiling to further elucidate the mechanisms underlying the MASLD-CHB interaction. Such studies could also explore the role of genetic and epigenetic factors in driving disease progression, offering insights into personalized treatment strategies. This study is not without limitations. The TriNetX analysis, while robust, is retrospective and may be subject to selection bias and diagnostic variability across healthcare organizations. The clinical cohort, although insightful, is limited by its small sample size (n=64 for CHB) and lack of longitudinal outcome data, which restricts causal inferences. Neither dataset assessed lifestyle factors such as diet or physical activity, which are known to influence MASLD and CHB progression [17]. Additionally, the absence of histologic data limits the precision of fibrosis staging, a common challenge in real-world studies [20]. Despite these constraints, the integration of real-world and clinical data provides a comprehensive view of MASLD’s impact on CHB, offering actionable insights for clinical practice. In conclusion, MASLD significantly exacerbates liver-related outcomes and reduces survival in CHB patients, despite effective HBV suppression with NA therapy, driven by increased fibrosis and metabolic burden. The synergy between viral and metabolic factors underscores the need for a holistic management approach that combines antiviral therapy with targeted interventions for metabolic risk factors. By addressing both components, clinicians can better mitigate the risk of liver complications and improve long-term outcomes for this vulnerable population. A cknowledgement We thank all the participating patients and the medical staff of the department of internal medicine at Wan Fang Hospital for their support. We acknowledge the TriNetX US Collaborative Network for providing the clinical database and analytical tools. We also thank Greg Matheson’s Editing Service and Wallace for their assistance with language editing. Statement of Ethics The TriNetX Cohort:TriNetX operates in compliance with the Health Insurance Portability and Accountability Act (HIPAA), the U.S. federal law that safeguards the privacy and security of healthcare data. Additionally, TriNetX is certified under the ISO 27001:2022 standard and maintains a comprehensive Information Security Management System (ISMS) to ensure the protection of healthcare data and adherence to the HIPAA Security Rule. Further information and documentation are available on the official TriNetX website. Verbal informed consent was obtained from the parent/legal guardian of participants prior to the study. This consent procedure and the clinical cohort protocol were reviewed and approved by the Institutional Review Board of Taipei Medical University, approval numbers: N201608026, N201605071, and N201805009, with informed consent obtained from all participants in accordance with the Declaration of Helsinki. Conflict of Interest Statement All authors have no conflicts of interest to declare. Funding Sources This research was funded by National Science and Technology Council, R.O.C, grant number NSTC 112-2320-B-038 -038 -MY3 and NSTC 113-2314-B-038-144-; and National Taipei University of Technology and Wan Fang Hospital, Taipei Medical University Joint Research Program, NTUT-WFTMU-113-01; and Wan Fang Hospital, Taipei Medical University, grant numbers 112-wf-eva-11 and 114-wf-eva-13 in Taiwan. The funder had no role in the design, data collection, data analysis, and reporting of this study. Author Contributions Conceptualization, SJ Shiue and MS Wu; collecting and interpreting data, SP Huang, SW Cheng, LW Wu, TS Chan, CN Chen, CL Cheng, YK lee, HY Yang, HS Shiue and MS Wu; formal analysis: HY Lin, SJ Shiue, KF Leng, HS Shiue and MS Wu; methodology: SJ Shiue and MS Wu; drafting the manuscript: SJ Shiue, HS Shiue and MS Wu; review and editing the manuscript: SP Huang, HY Lin and MS Wu. All authors have read and agreed to the published version of the manuscript. Data Availability Statement All Data is contained within the article. Further enquiries can be directed to the corresponding author. References 1. Global, regional, and national burden of hepatitis B, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Gastroenterol Hepatol. 2022 Sep;7(9):796-829.2. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. 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Table 1: Baseline Characteristics After Propensity Score Matching Age (years, mean ± SD) 55.2 ± 11.4 55.7 ± 12.1 0.027 Male (%) 65.8 67.7 0.058 BMI (kg/m², mean ± SD) 29.2 ± 7.2 23.7 ± 3.7 <0.001 ALT (U/L, mean ± SD) 46.7 ± 48.6 40.5 ± 44.6 0.075 Albumin (g/dL, mean ± SD) 4.2 ± 0.5 4.1 ± 0.5 0.005 Variables include age, sex, body mass index (BMI), alanine aminotransferase (ALT), and albumin levels, with mean ± standard deviation (SD) or percentage shown for each group. Table 2: Cox Proportional Hazards Model CHB-MASLD-NA (vs. CHB alone-NA) 1.547 1.453–1.648 <0.001 Male sex 1.546 1.451–1.647 <0.001 Age 1.028 1.025–1.030 <0.001 HBV DNA Viral Load 1.000 1.000–1.000 0.590 Hazard ratios (HR), 95% confidence intervals (CI), and p-values are shown for each covariate, including MASLD status (CHB-MASLD-NA vs. CHB alone-NA), male sex, age, and HBV DNA viral load. Table 3: Clinical Cohort Parameters stratified by CAP (Controlled Attenuation Parameter) CAP 237.615 ± 2.371 283.176 ± 5.786 336.850 ± 7.277 238.308 ± 2.834 275.259 ± 2.402 340.134 ± 3.038 Liver Stiffness (kPa) 7.931 ± 0.847 9.853 ± 1.668 9.150 ± 0.946 5.262 ± 0.544 4.952 ± 0.317 6.228 ± 0.256 BMI (kg/m²) 25.240 ± 0.787 25.585 ± 0.914 29.148 ± 0.884 25.527± 0.924 26.793± 0.776 29.447± 0.509 TG (mg/dL) 113.778 ± 9.123 125.900 ± 9.719 126.286 ± 14.346 129.923 ± 15.261 118.593 ± 9.439 172.639 ± 8.262 HbA1c (%) 5.072 ± 0.123 5.072 ± 0.208 6.231 ± 0.416 5.108 ± 0.193 5.189 ± 0.133 5.672 ± 0.085 UA (mg/dL) 5.577 ± 0.363 5.959 ± 0.289 6.360 ± 0.320 5.362 ± 0.487 5.411 ± 0.239 5.934 ± 0.117 HBsAg (log IU/mL) 2.722 ± 0.220 2.588 ± 0.208 2.539 ± 0.163 - - - Parameters include Controlled Attenuation Parameter (CAP), liver stiffness, body mass index (BMI), triglycerides (TG), hemoglobin A1c (HbA1c), uric acid (UA), and hepatitis B surface antigen (HBsAg) levels. Data are shown as mean ± standard error. Figure Legends Fig. 1. MASLD is associated with significantly reduced 10-year survival in CHB patients receiving nucleos(t)ide analogue (NA) therapy. Kaplan-Meier analysis revealed a lower 10-year survival probability in CHB-MASLD-NA (61.45%, green line) vs. CHB alone-NA (79.30%, purple line), log-rank χ² = 66.911, p<0.001. Fig. 2. CHB-MASLD-NA group showed significantly increased advanced fibrosis prevalence. The distribution of liver fibrosis stages among MASLD without CHB, CHB-alone-NA and CHB-MASLD-NA groups. The bars represented the distribution of liver fibrosis stages within each group. F0, F1, F2-3 and F4 for no fibrosis, mild fibrosis, moderate fibrosis and advanced fibrosis for CHB patients, respectively. Information & Authors Information Version history V1 Version 1 06 October 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Collection Journal of Medical Virology Keywords biostatistics & bioinformatics digestive system hepatitis b virus pathogenesis survival analysis virus classification Authors Affiliations Sheng-Jie Shiue Taipei Municipal Wan Fang Hospital View all articles by this author Dr. Chao-Ling Cheng Taipei Municipal Wan Fang Hospital View all articles by this author Sheng-Wei Cheng Taiwan Adventist Hospital View all articles by this author Dr. Chun‐Nan Chen Taipei Municipal Wan Fang Hospital View all articles by this author Shih-Ping Huang Taipei Municipal Wan Fang Hospital View all articles by this author Yan Kang Lee Taipei Municipal Wan Fang Hospital View all articles by this author Li-Wei Wu National Taiwan University Hospital Department of Internal Medicine View all articles by this author Han-Shiang Shiue Taipei Municipal Wan Fang Hospital View all articles by this author Tze-Sian Chan Taipei Municipal Wan Fang Hospital View all articles by this author Hsin-Yi Lin National Taipei University of Technology View all articles by this author Dr. Hsien-Yao Yang Taipei Municipal Wan Fang Hospital View all articles by this author Kuo-Feng Leng Taipei Municipal Wan Fang Hospital View all articles by this author Dr. Ming Shun Wu 0000-0002-5755-9062 [email protected] Taipei Municipal Wan Fang Hospital View all articles by this author Metrics & Citations Metrics Article Usage 248 views 116 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Sheng-Jie Shiue, Dr. Chao-Ling Cheng, Sheng-Wei Cheng, et al. 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