Baseline liver fibrosis severity predicts treatment response in patients with HBeAg-positive CHB

Background and aims

The impact of baseline liver fibrosis severity on the effectiveness of pegylated interferon (Peg-IFN) combined with nucleos(t)ide analogs (NAs) in the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) has not been fully clarified. This study aimed to investigate whether the effectiveness of this combination therapy differed according to the severity of baseline liver fibrosis.

Methods

A total of 172 HBeAg-positive CHB patients receiving Peg-IFN plus NAs were stratified according to non-invasive fibrosis markers (aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 index [FIB-4]) into three groups: no significant fibrosis (n = 75), significant fibrosis (n = 70), and advanced fibrosis/cirrhosis (n = 27). The primary outcome was the HBeAg clearance rate at 24 months of treatment. Secondary outcomes included the hepatitis B surface antigen (HBsAg) clearance rate, the rate of HBsAg level decline > 1.0 log₁₀, virological response, and improvement in non-invasive fibrosis indices.

Results

At 24 months, HBsAg clearance and complete virological response rates were comparable across the three groups. Cumulative HBeAg clearance rates differed significantly (log-rank P = 0.027): 16.00%, 30.00%, and 40.74% in the three groups, respectively, with Group 3 higher than Groups 1 and 2. Multivariate analysis identified a significantly higher likelihood of HBeAg clearance in Group 3 versus Group 1 (adjusted odds ratio = 6.373, 95% confidence interval: 1.288–31.531, P = 0.023). Additionally, analysis of liver fibrosis outcomes showed that patients with more severe baseline fibrosis had a higher proportion of improvement in non-invasive fibrosis indices, with 95.00% in Group 3, while 42.98% of the overall cohort achieved fibrosis improvement.

Conclusions

This study demonstrates that baseline liver fibrosis severity is a key independent factor in predicting treatment response to Peg-IFNα plus NAs in patients with HBeAg-positive CHB. Patients with more advanced fibrosis achieved higher rates of HBeAg clearance and substantial improvements in non-invasive fibrosis indices. The robustness of these primary conclusions was supported by sensitivity analyses. These results suggest that baseline fibrosis assessment has clinical value in optimizing patient selection for Peg-IFN-based combination therapy. Future prospective, multicenter studies with long-term follow-up and incorporation of histological or multi-omics approaches are warranted to validate these findings and elucidate the underlying mechanisms.