Regression of Liver Fibrosis in Patients on Hepatitis B Therapy Is Associated With Decreased Liver-Related Events

Abstract

Background and AimsLiver fibrosis in patients with chronic hepatitis B (CHB) can regress with successful antiviral therapy. However, the long-term clinical benefits of fibrosis regression have not been fully elucidated. This study investigated the association between biopsy-proven fibrosis regression by P-I-R score and liver-related events (LREs) in CHB patients. MethodsPatients with on-treatment liver biopsy and significant fibrosis/cirrhosis (Ishak ≥ stage 3) were included in this analysis. Fibrosis regression was evaluated according to the P-I-R score of the Beijing Classification. LREs were defined as decompensations, hepatocellular carcinoma (HCC), liver transplantation, or death. Cox proportional hazards model was used to determine associations of fibrosis regression with LREs. ResultsA total of 733 patients with Ishak stage 3/4 (n = 456, 62.2%) and cirrhosis (Ishak stage 5/6, n = 277, 37.8%) by on-treatment liver biopsy were enrolled. According to the P-I-R score, fibrosis regression, indeterminate and progression were observed in 314 (42.8%), 230 (31.4%), and 189 (25.8%) patients, respectively. The 7-year cumulative incidence of LREs was 4.1%, 8.7%, and 18.1% in regression, indeterminate, and progression, respectively (Log-rank, P < .001). Compared to patients with fibrosis progression, those with fibrosis regression had a lower risk of LREs (adjusted HR = 0.40, 95%CI: 0.16-0.99, P = .047), followed by indeterminate group (adjusted HR = 0.86, 95%CI: 0.40 - 1.85, P = .691). Notably, this favorable association was also observed in patients with cirrhosis or low platelet counts (< 150×109/L). ConclusionsAntiviral therapy-induced liver fibrosis regression assessed by P-I-R score is associated with reduced liver-related events. This shows the utility of histologic fibrosis regression assessed by on-treatment P-I-R score as a surrogate endpoint for clinical events in patients with HBV-related fibrosis or early cirrhosis.