Characterizing Unique Clinical and Virological Profiles in Concurrent Chronic Hepatitis B and Metabolic Dysfunction-Associated Liver Disease: Insights from a Population-Based Cohort Study

<b>Background:</b> The concurrent presence of chronic hepatitis B virus (CHB) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) presents a unique clinical scenario with implications that are not yet fully understood. This study aims to characterize the distinct clinical and virological features of CHB in the context of MASLD and evaluate its impact on disease progression and outcomes. <b>Methods:</b> Utilizing a comprehensive health maintenance organization database, this study included 1186 patients with CHB from 2000-2020. Patients were categorized into two groups: CHB-MASLD (<i>n</i> = 188) and CHB alone (<i>n</i> = 998). CHB diagnosis was confirmed by serological markers, while MASLD was diagnosed based on imaging and cardiometabolic risk factors. Comparative analysis and multiple regression models were applied to assess variables related to viral parameters and clinical outcomes. <b>Results:</b> The CHB-MASLD group was older (mean age of 45.2 vs. 39.1, <i>p</i> < 0.001) with higher rates of obesity (46.8% vs. 23.8%, <i>p</i> < 0.001), diabetes (36.2% vs. 17.3%, <i>p</i> < 0.001), and dyslipidemia. Distinct viral profiles included higher HBeAg negativity (96.2%), a higher rate of HBeAg-negative infection (70.4% vs. 63.8%; <i>p</i> < 0.001), and increased HBeAg seroconversion under treatment. Cirrhosis was more prevalent in the CHB-MASLD group (9.6% vs. 4.4%, <i>p</i> = 0.007), while HCC rates were comparable. Multivariate analysis identified age, male gender, chronic active hepatitis, and diabetes as predictors of cirrhosis. <b>Conclusions:</b> CHB-MASLD patients were distinguished by a higher prevalence of metabolic features, along with a distinct viral profile marked by increased chronic HBeAg infection, higher rates of HBeAg seroconversion, and a potential association with worse disease outcomes.