Efficacy and Metabolic Effects of Pegylated Interferon α-2b versus Nucleos(T)ide Analogues in Patients with Chronic Hepatitis B and Concomitant Metabolic Dysfunction-Associated Steatotic Liver Disease: A Retrospective Study.

AIM OF THE STUDY: CHB and MASLD are increasingly prevalent coexisting conditions that accelerate liver fibrosis progression and increase hepatocellular carcinoma risk. This study aimed to compare the antiviral efficacy and metabolic effects of PEG-IFNα-2b versus nucleos(t)ide analogues (NAs) in patients with the CHB-MASLD comorbidity. METHODS: This retrospective study enrolled 174 biopsy-confirmed CHB-MASLD patients treated at Xiamen Hospital of Traditional Chinese Medicine between July 2019 and July 2024. Patients received either PEG-IFNα-2b (n = 87) or NAs (n = 87) for ≥ 48 weeks. Primary outcomes included HBsAg seroclearance and quantitative reduction. Metabolic parameters, liver stiffness measurement (LSM), and controlled attenuation parameter (CAP) were assessed at baseline, 24 weeks, and 48 weeks. Multivariate linear regression was performed to evaluate treatment effects on metabolic changes, adjusting for baseline values, age, sex, HBeAg status, and BMI. RESULTS: At 48 weeks, PEG-IFNα-2b achieved significantly higher HBsAg seroclearance rates compared with NAs (P < 0.05) and a greater log reduction in HBsAg levels (P < 0.001). PEG-IFNα-2b also demonstrated superior metabolic benefits: significant reductions in total cholesterol (P < 0.001), LDL-cholesterol (P < 0.001), BMI (P < 0.001), and CAP values at 48 weeks (P < 0.05). However, PEG-IFNα-2b was associated with decreased HDL-cholesterol levels and a higher incidence of transient aminotransferase elevations (P < 0.001). CONCLUSION: In CHB-MASLD patients, PEG-IFNα-2b provides better virological response and favorable metabolic modulation, supporting it may represent a promising treatment option.