Ishak stage 6 fibrosis is more likely to regress than stage 5 in CHB patients undergoing entecavir therapy

BACKGROUND: Chronic hepatitis B (CHB) patients with milder baseline fibrosis have traditionally been considered more likely to achieve histological improvement after antiviral therapy. However, our previous finding suggests that patients with Ishak stage 6 may have greater potential for fibrosis regression than those with stage 5. This study aimed to evaluate whether CHB patients with Ishak stage 6 are more likely to achieve fibrosis regression than those with stage 5 after entecavir (ETV) monotherapy or ETV in combination with Biejia-Ruangan (ETV + BR) therapy. METHODS: Baseline Ishak fibrosis stage served as the main analytic variable, while the use of concomitant traditional Chinese medicine was included as a stratification factor. Demographic characteristics, viral markers, and baseline laboratory parameters were incorporated as covariates. A logistic regression model was applied to evaluate the association between baseline Ishak stage and fibrosis regression. Based on this model, a sensitivity analysis was further performed in the subgroup of patients with baseline Ishak stage 5 or 6 to assess the robustness of the findings. A generalized additive model (GAM) was additionally applied to explore potential non-linear stage-related patterns. RESULTS: A total of 705 patients had paired biopsy data. The fibrosis regression rate was 50.21% in stage 6 versus 45.58% in stage 5. In the multivariable logistic regression analysis, baseline Ishak stage 6 was associated with a higher likelihood of fibrosis regression compared with stage 5 (OR:1.612, 95%CI:1.027 ~ 2.529, p = 0.038). GAM analysis revealed a stage-related, non-linear trajectory with a nadir at stage 5 and an upward trend at stage 6. Sensitivity analyses yielded consistent results (OR: 1.835, 95%CI: 1.148 ~ 2.931, p = 0.011). CONCLUSION: Among CHB patients treated with ETV, those with baseline Ishak stage 6 were more likely to achieve histological fibrosis regression than those with stage 5. CLINICAL TRIAL REGISTRATION: Identifier NCT01965418.