Impact of Non‐Alcoholic Fatty Liver Disease on the HBsAg Loss of Patients With Chronic Hepatitis B Treated in Pegylated Interferon Alpha

Whether combining non‐alcoholic fatty liver disease (NAFLD) affects the efficacy of pegylated interferon alpha (PEG‐IFN‐α) for patients with chronic hepatitis B (CHB) remains unknown; hence, we aimed to conduct a retrospective cohort study to investigate the impact of NAFLD on the HBsAg loss rate of CHB treated with PEG‐IFN‐α. A total of 279 adult CHB patients receiving antiviral therapy with PEG‐IFN‐α were included in the study, of which 94 (33.7%) patients had combined NAFLD. The median treatment duration in the overall population was 37 (23, 59) weeks, and 79 (28.3%) patients achieved serum HBsAg loss during treatment. Compared to patients without NAFLD, patients with NAFLD had lower baseline HBsAg levels prior to treatment with PEG‐IFN‐α (438.05 [152.77, 978.60] vs. 296.60 [54.20, 647.15] IU/mL, p = 0.004). Propensity score matching (PSM) was applied to rectify the baseline characteristics between the two groups, including age, gender and quantitative HBsAg level. After PSM, 84 CHB with NAFLD and 84 CHB without NAFLD were included in the matched cohort. With a comparable treatment duration in both groups, the patients with NAFLD had a lower cumulative HBsAg loss rate (Log‐rank p = 0.007). Multivariable analysis suggested that NAFLD was independently associated with a decrease in HBsAg loss rates (risk ratio HR = 0.505; 95% CI, 0.283–0.902; p = 0.021), which was consistent in sensitivity analyses that included only nucleos(t)ide analogue (NA)–treated patients. In conclusion, CHB with NAFLD demonstrated a lower HBsAg loss rate during PEG‐IFN‐α treatment, suggesting that more optimal therapeutic strategies need to be further explored.