Histological responses of peginterferon alpha add‐on therapy in patients with chronic hepatitis B with advanced liver fibrosis after long‐term nucleos(t)ide analog treatment

: Although long-term antiviral treatment with nucleos(t)ide analogs (NAs) can lead to histological improvement in patients with chronic hepatitis B (CHB), a substantial proportion of patients still fail to achieve regression of fibrosis. Here, we investigated whether peginterferon alpha (Peg-IFNα） add-on therapy had benefits on fibrosis regression in patients with sustained severe fibrosis even after long-term NA treatment. We conducted a retrospective analysis of data from 50 patients with CHB receiving 48 weeks of Peg-IFNα add-on therapy. All enrolled patients had advanced fibrosis or cirrhosis (S score ≥ 3) at baseline and underwent NA treatment for at least 1 year before Peg-IFNα addition. Paired liver biopsies before and after Peg-IFNα add-on treatment and laboratory tests at baseline, 24 weeks of treatment, 48 weeks of treatment and long-term follow-up were analysed. Of the 50 patients enrolled in this study, 34 patients (68.0%) had significant regression of fibrosis, and 42 (84.0%) showed significant remission of inflammation after Peg-IFNα add-on treatment. Compared with nonresponders, patients with significant histological improvement showed faster hepatitis B surface antigen (HBsAg) decline and tended to have higher cumulative hepatitis B e antigen (HBeAg) and HBsAg loss rates during long-term follow-up. Peg-IFNα add-on therapy led to significant regression of fibrosis and resolution of inflammation in patients with advanced fibrosis after long-term NA treatment.