Pathological Evaluation of Liver Regeneration Post-Direct-Acting Antiviral Therapy in Hepatitis B.

Abstract

Background and Aims: The regenerative capacity of the liver following direct-acting antiviral (DAA) therapy in chronic hepatitis B remains incompletely understood. This study aimed to evaluate pathological changes and regenerative responses in liver tissue following DAA therapy.

Methods: This prospective study analyzed paired liver biopsies from 120 chronic hepatitis B patients at baseline and 48 weeks post-DAA therapy. Comprehensive histological assessment, immunohistochemical analysis of regenerative markers, and molecular profiling of regeneration-associated genes were performed.

Results: Significant improvements in histological parameters were observed, with 60% of patients showing fibrosis regression. Ki-67-positive hepatocytes increased from 2.1% to 8.4% (p<0.001), accompanied by enhanced expression of progenitor cell markers. Molecular analysis revealed upregulation of key regenerative genes (HGF: 3.2-fold, c-Met: 2.8-fold) and concurrent downregulation of inflammatory cytokines. Multivariate analysis identified age <40 years (OR 2.4, 95% CI 1.8-3.2), lower baseline fibrosis (OR 2.1, 95% CI 1.6-2.7), and BMI <25 kg/m² (OR 1.5, 95% CI 1.1-2.0) as predictors of enhanced regenerative response.

Conclusions: DAA therapy in chronic hepatitis B promotes significant liver regeneration, characterized by coordinated molecular and cellular responses. Early therapeutic intervention, particularly in younger patients with minimal fibrosis, may optimize regenerative outcomes.