What question did this study set out to answer?

The study aims to evaluate if Ishak stage 6 patients are more likely to experience fibrosis regression compared to stage 5 after treatment with entecavir.

March 12, 2026Open Access

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

Key Points

The study aims to evaluate if Ishak stage 6 patients are more likely to experience fibrosis regression compared to stage 5 after treatment with entecavir.
Patients were classified based on baseline Ishak fibrosis stage.
Logistic regression was used to analyze the association between fibrosis stage and regression.
Demographic, viral markers, and lab parameters were included as covariates.
Sensitivity analyses were performed focusing on patients with stage 5 or 6.
A generalized additive model was used to identify non-linear patterns related to fibrosis stages.
Fibrosis regression rate was 50.21% in stage 6 and 45.58% in stage 5.
Ishak stage 6 was associated with a higher likelihood of regression, with an odds ratio of 1.612.
Sensitivity analysis also supported the findings, showing an odds ratio of 1.835 for stage 6.

Abstract

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.

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