ETV add-on Peg-interferon therapy plays a positive role in reversing hepatic fibrosis in treatment-naïve chronic hepatitis B patients: a prospective and randomized controlled trial

Abstract Background and Aim The efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding Peg-interferon to ongoing ETV treatment leads to a better curative effect or not. Methods Eligible HBV patients (n=144) were randomly divided (1:1) to receive either ETV monotherapy (n=70) or peg-interferon add-on therapy from weeks 26 to 52 (n=74). Patients were followed-up for 2 years. We evaluated hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response (SVR), transient elastography value, and histological scores. Results At week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase (ALT)and aspartate aminotransferase (AST) levels and transient elastography values decreased significantly compared with baseline. Both group showed a favorable decrease in alpha fetoprotein(AFP) (monotherapy:23.4±77.3 vs 2.4±0.91, P=0.149; combination therapy: 33.3±96.9 vs 4.3±5.5,P=0.085) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group(mean transient elastography value 7.5±3.4 kPa [SD 1.9] vs. 12.8±13.9 kPa [SD 1.9], P=0.037). But this research didn’t show significant difference in HBsAg conversion rate (1.79% (1/56) vs 4.11% (3/73), P=0.632) as well as HBV-DNA sustained virologic response(93.2% vs 98.5%,P=0.15) between two groups. Conclusions Both therapies supported liver function recovery and histology improvement. Combination therapy did not show better antiviral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.