Addition of nucleoside analogues to peg-IFNα-2a enhances virological response in chronic hepatitis B patients without early response to peg-IFNα-2a: A randomized controlled trial

Abstract

Background: Current treatments for chronic hepatitis B (CHB) include pegylated interferon alpha (PEG-IFN-α) which is an immune modulator, and nucleos(t)ide analogs (NAs) which directly inhibit HBV DNA polymerase. With the limited efficacy of PEG-IFN-α and prolonged treatment periods associated with NAs, there is an urgent need for novel therapeutic strategies, especially for patients with a poor early response to anti-viral therapy. Methods: In this study, 178 patients with chronic hepatitis B (n=131) and compensated (n=47) HBV-induced cirrhosis were enrolled, 120 patients with HBeAg (+). All the patients were treated for 12weeks with PEG-IFN-α. Among them, a total of 138 patients with a poor virological response after 12weeks were treated for an additional 48weeks with Peg-IFNα-2a (control) (n=43), with Peg-IFNα-2a+entecavir (ETV) (n=49), or Peg-IFNα-2a+adefovir dipivoxil (ADV) (n=46), and were followed for 48weeks after therapy. Early virological response was defined as undetectable HBV DNA after anti-viral therapy for 12weeks. Sustained virological response (SVR) was defined as no change in therapeutic effectiveness after 6months follow-up, and no recurrence.Therapeutic efficacy was determined by evaluating HBV DNA levels, serum and liver HBsAg levels, liver function tests and liver histology. Results: Patients in the Peg-IFNα-2a+ETV and Peg-IFNα-2a+ADV groups showed a significantly greater decrease in HBV DNA levels over time, and a significantly higher SVR compared to patients receiving Peg-INFα-2a monotherapy (both P values <0.05). Although patients receiving combination therapy had a significantly higher change in serum HBsAg levels compared to the monotherapy group, there was no significant difference in liver HBsAg levels between the three treatment groups. Conclusion: This study demonstrated that in patients with a poor virological response after 12weeks of treatment with Peg-IFNα-2a alone, addition of ADV or ETV significantly reduced HBV DNA levels, serum HBsAg levels, and increased SVR. Individualization of anti-viral therapy would ensure that only patients who do not respond to Peg-IFNα-2a would receive combination therapy. Our data have important implications for the treatment of CHB patients who fail to show an early response to Peg-IFNα-2a monotherapy. Trial registration: This trial was retrospectively registered on 2012 May 24 at the China Clinical Trials Registry (ChiCTR-OCC-12002196).