Incidence and Resolution of Steatohepatitis in Patients Receiving Entecavir for Chronic Hepatitis B

Abstract

Background: Although concomitant non-alcoholic steatohepatitis (NASH) is common in chronic hepatitis B (CHB) patients, the outcome of NASH in CHB patients remains unclear. This study was aimed to evaluate the incidence and resolution rate of NASH in CHB patients during antiviral treatment. Methods: This was a sub-study of a multicenter prospective study on HBV treatment outcomes including patients with or without NASH. The histopathological features of NASH were examined using paired liver biopsies at baseline and week 72. Finally, 297 of 1000 CHB patients (30%) had concomitant steatosis, 182 (18·2%) had NASH. Findings: After 72-week entecavir treatment, concomitant steatosis and NASH decreased to 18% (129/727) and 10% (73/727), respectively. Among patients with NASH, the scores of hepatic steatosis, ballooning, lobular inflammation and fibrosis stages all improved (all P<0.001), and 63 of 136 patients (46%) achieved NASH resolution. By multivariable analysis, baseline body mass index (BMI) <23 kg/m2 (OR=2·4, 95% CI: 1·112-5·255, P=0.012) and no weight gain at follow-up (OR=5·4, 95% CI: 1·443-19·896, P=0·026) were significantly associated with NASH resolution. The rates of serum HBeAg loss, HBeAg seroconversion, undetectable HBV DNA and ALT normalization were similar between patients with or without NASH (P=0·303, 0·652, 0·498 and 0·736, respectively). Among patients who had no or bland steatosis at baseline, 22 cases (3·7%) had incident NASH. Baseline BMI ≥23 kg/m2 (OR=12·5, 95%CI: 2·813-55·606, P=0·001) and weight gain (OR=5·1, 95%CI: 1·674-15·694, P=0·005) were predictors of NASH development. Interpretation: CHB patients had a high proportion of NASH resolution during antiviral treatment, especially in lean patients without weight gain. The value of weight management in CHB patients during antiviral treatment deserves further evaluation. Trial Registration: NCT01965418 Funding Statement: This study was funded by the State Key Projects Specialized on Infectious Disease, Chinese Ministry of Science and Technology (2013ZX10005002; 2018ZX10725506). Declaration of Interests: All the authors declare that they have no conflict of interest. Ethics Approval Statement: The study protocol was approved by the ethics committee of each participating institution and written informed consents were obtained from all patients. The study conformed to the ethical guidelines of the 1975 Declaration of Helsinki. Study protocol was approved by the Chinese PLA General Hospital Ethics Review Committee (2013145D).