Xu Y, et al. - In view of limited efficacy of pegylated interferon alpha (PEG-IFN-α) and prolonged treatment periods associated with nucleos(t)ide analogs (NAs), novel therapeutic strategies, especially for patients with a poor early response to anti-viral therapy had been sought for. In this study, patients with a poor virological response after 12 weeks of treatment with Peg-IFNα-2a alone indicated a significant reduction in HBV DNA levels, serum HBsAg levels, and an increase in sustained virological response (SVR) with the addition of adefovir dipivoxil (ADV) or entecavir (ETV). Individualization of anti-viral therapy would ensure that only patients who do not respond to Peg-IFNα-2a would receive combination therapy. The data seemed to have important implications for the treatment of chronic hepatitis B (CHB) patients who fail to show an early response to Peg-IFNα-2a monotherapy.

Methods

• Authors enrolled 178 patients with chronic hepatitis B (n = 131) and compensated (n = 47) HBV-induced cirrhosis; 120 patients were HBeAg (+).
• They treated all the patients for 12 weeks with PEG-IFN-α.
• Among them, 138 patients with a poor virological response after 12 weeks were provided an additional 48 weeks treatment with Peg-IFNα-2a (control) (n = 43), with Peg-IFNα-2a + entecavir (ETV) (n = 49), or Peg-IFNα-2a + adefovir dipivoxil (ADV) (n = 46); these patients were followed for 48 weeks after therapy.
• They defined early virological response as undetectable HBV DNA after anti-viral therapy for 12 weeks.
• They defined sustained virological response (SVR) as no change in therapeutic effectiveness after 6 months follow-up, and no recurrence.
• Determination of therapeutic efficacy was performed 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 indicated a markedly higher decline in HBV DNA levels over time, and a markedly greater SVR compared to patients receiving Peg-INFα-2a monotherapy (both P values <0.05).
• Although patients receiving combination therapy had a markedly higher change in serum HBsAg levels compared to the monotherapy group, observations suggested no marked difference in liver HBsAg levels between the three treatment groups.