Changes in Liver Fibrosis in Patients with Chronic Hepatitis B Treated with Pegylated Interferon Combined with Oral Antiviral Agents: A 48-Week Observation from a Prospective Cohort Study

Background and Aims: Pegylated interferon (PEG-IFN) combined with oral antiviral agents is currently the most widely used and highly effective treatment regimen for chronic hepatitis B virus (HBV) infection. While effectively suppressing HBV replication, its impact on liver histopathological fibrosis and inflammation remains a critical concern for clinicians and patients. Methods : A total of 625 patients who completed 48 weeks of PEG-IFN combined with oral antiviral therapy were enrolled in this real-world study. Based on their virological response at 48 weeks, patients were categorized into Clearance group and Non-clearance group. Changes in liver biochemistry, fibrosis, and renal function were compared between groups and before/after treatment. Results: No significant differences were observed in baseline blood tests, liver biochemical markers, or histopathological features between the Clearance group and Non-clearance group. Similarly, baseline renal function showed no significant variation. Further analysis revealed that the Clearance group exhibited significant aggravation of liver fibrosis after 48 weeks of treatment, which correlated strongly with alterations in liver enzyme levels. However, one patient who underwent paired liver biopsies before and after treatment demonstrated marked histopathological improvement in fibrosis. This finding underscores the irreplaceable role of liver histopathology in assessing fibrosis and inflammation. Conclusion: PEG-IFN combined with oral antiviral therapy exerts favorable effects on liver fibrosis and inflammation in chronic HBV patients. Non-invasive fibrosis assessment models can monitor fibrotic progression but are susceptible to confounding by hepatic inflammation.