OBJECTIVETo investigate the efficacy of a 96-week course of nucleos(t)ide analogue and interferon (IFN) combination therapy for achieving seroconversion at 24 weeks after completion in patients with chronic hepatitis B (CHB).

METHODSOne-hundred-and-thirty-five CHB patients with positivity for hepatitis B e antigen (HBeAg) were recruited for study between January 2005 and December 2008. All patients were given a 96-week course of nucleos(t)ide analogue (lamivudine or adefovir dipivoxil) alone (monotherapy controls, n = 45) or in combination with IFN or Pegylated-IFN-alpha-2a (Peg-IFNa-2a) (n = 90). At treatment weeks 12, 24, 48, 72, and 96, and at 24 weeks after treatment completion, serum samples were collected from all patients for assessment of biochemical, virological and serological responses to treatment. The biochemical response was indicated by normalization of the alanine aminotransferase (ALT) level. The virologic response was indicated by a reduction in the hepatitis B virus (HBV) DNA level to less than 1000 copies/ml. The serological response was indicated by seroconversion of either HBeAg or hepatitis B surface antigen (HBsAg). Statistical analysis was performed with the Chi-squared test.

RESULTSAmong the patients treated with nucleos(t)ide analogue and IFN combination therapy, 41.1% (37/90) achieved HBeAg seroconversion and 18.9% (17/90) achieved HBsAg seroconversion at the end of treatment. However, significantly less of the patients treated with nucleos(t)ide analogue monotherapy achieved HBeAg seroconversion and none achieved HBsAg seroconversion by end of treatment (33.3% and 0%, respectively; x2= 8.08, P less than 0.01 vs. the combination therapy group). Age stratification of the 17 HBsAg-seroconverted patients treated with combination therapy indicated that the HBsAg seroconversion rate was significantly higher in patients less than 30-years-old than those 30 and older (x2= 12.62 and 4.24, respectively, P less than 0.05). At post-treatment week 24, the 17 HBsAg-seroconverted patients treated with combination therapy showed HBsAg titers of less than 250 IU/ml; moreover, 11.8% (2/17) of these patients remained HBeAg-positive and 17.6% (3/17) showed abnormal ALT levels and elevated HBV DNA.

CONCLUSIONProlonged nucleos(t)ide analogue plus IFN combination therapy can significantly improve the rate of HBsAg seroconversion in HBeAg-positive CHB patients, and this treatment regimen is especially efficacious in patients under the age of 30.