Hydronidone for the Treatment of Liver Fibrosis Related to Chronic Hepatitis B: A Phase 2 Randomized Controlled Trial

• Published in: Clinical gastroenterology and hepatology Vol. 21; no. 7; pp. 1893 - 1901.e7
• Main Authors: Cai, Xiaobo, Liu, Xuehan, Xie, Wen, Ma, Anlin, Tan, Youwen, Shang, Jia, Zhang, Jiming, Chen, Chengwei, Yu, Yanyan, Qu, Ying, Zhang, Ling, Luo, Ying, Yin, Ping, Cheng, Jun, Lu, Lungen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2023
• Subjects: Chronic Hepatitis B; Gastroenterology and Hepatology; Hydronidone; Liver Fibrosis; Regression; Chronic Hepatitis B; AST; Hydronidone; CI; HBeAg; LSM; Regression; ICC; ITT; ALT; HBsAg; Liver Fibrosis; RC; NA; PC; RF; PF; TBil; ULN; TGF-β; SAEs; CHB; HBV; hepatitis B virus e antigen; total bilirubin; hepatitis B virus; progression to cirrhosis; regression of cirrhosis; intention-to-treat; transforming growth factor-beta; progression of fibrosis; alanine transaminase; intraclass correlation coefficient; serious adverse events; nucleos(t)ide analogue; liver stiffness measurement; hepatitis B surface antigen; regression of fibrosis; upper limit of normal; confidence interval; aspartate transaminase
• ISSN: 1542-3565; 1542-7714; 1542-7714
• DOI: 10.1016/j.cgh.2022.05.056

Hepatitis B virus infection frequently leads to liver fibrosis and is the leading cause of hepatocellular carcinoma and cirrhosis in Asia Pacific. Pirfenidone is approved by the United States Food and Drug Administration for treatment of idiopathic pulmonary fibrosis, and hydronidone is a novel structural modification of pirfenidone with the aim of reducing hepatoxicity. We aimed to investigate the safety and efficacy of hydronidone in patients with chronic hepatitis B (CHB)-associated liver fibrosis. This was a 52-week multicenter, randomized, double-blind, placebo-controlled, phase II study at 8 centers in China. Patients with CHB with biopsied documented liver fibrosis were eligible and were randomly assigned into receiving daily placebo or hydronidone orally (180 mg/day, 270 mg/day, or 360 mg/day). All enrolled subjects also received entecavir 0.5 mg/day. A second liver biopsy was performed at week 52. The primary endpoint was defined as fibrosis improvement (reduction of at least 1 Ishak score at week 52 of treatment). From June 25, 2015, to September 5, 2019, 168 patients with CHB and liver fibrosis met the inclusion/exclusion criteria and were subsequently randomized, 43 in the placebo group and 125 in the hydronidone groups (42 in the 180-mg group, 42 in the 270-mg group, and 41 in the 360-mg group). The fibrosis improvement endpoint was achieved by 11 patients (25.6%) in the placebo group and 17 patients (40.5%) in the 180-mg group (P = .12), 23 patients (54.8%) in the 270-mg group (P = .006), and 18 patients (43.90%) in the 360-mg group (P = .08). The improvement rate was 58 of 125 (46.4%) in the combined hydronidone group (P = .014). The overall safety profile and incidence of serious adverse events were similar among the groups. Hydronidone plus entecavir showed clinically significant histological improvement of liver fibrosis in patients with CHB, and the dose of 270 mg showed the best efficacy of fibrosis regression. Further studies are required to assess the long-term effectiveness of hydronidone in regression of hepatic fibrosis. ClinicalTrials.gov number, NCT02499562.