The Efficacy Of Adefovir Dipivoxil Add-on Therapy In HBeAg Positive Chronic Hepatitis B Patients With Poor Virological Response To Peg-IFN-α

Aim: To investigate the efficacy of Peg-interferon alpha(Peg-IFN α) add-on adefovir dipivoxil in hepatitis B e antigen(HBe Ag) positive chronic hepatitis B(CHB) with a poor virological response to Peg-IFN α, explore the factors that influenced the efficacy of patients.Methods: A total of 74 HBe Ag positive chronic hepatitis B patients who did not acquire early virological response(HBV DNA≥105copies/m L) achieving Peg-IFN α treatment in the first affiliated hospital of Fujian medical university from September, 2009 to January, 2014 were collected. Three groups were categorized by different treatment regimes. 36 patients combined with adefovir dipivoxil at week 12(A group), 19 patients combined with adefovir dipivoxil at week 24(B group) and 19 patients achieved Peg-IFN α monotherapy. The rate of ALT normalization, HBV DNA negative, HBe Ag seroconversion, HBs Ag clearance and seroconversion were compared between three groups at the end of treatment. Date was analyzed using t test, chi-square test and Cox logistic regressions. SPSS software was used for statistical analysis.Results: At week 48, the rate of combined response of group A was 27.78%, significantly higher than group B and C(27.78%vs5.26%,P=0.031; 27.78%vs5.26%,P=0.031). The rates of HBV DNA undetectable were 66.67%, 52.63% and 32.84% for patients of Group A, B and C, respectively. At the end of the treatment, the rates of ALT normalization were 86.11%, 73.68%, 42.11% in Group A, B and C. The comparison the rate of HBV DNA undetectable and ALT normalization between Group A and Group C was significantly different(P<0.05). HBe Ag seroconversion rate was 27.78% in Group A, and 15.79% in Group B, C, which were no significant different(P=0.320). Two patients had HBs Ag clearance and seroconversion at the end of therapy. There were no adverse events had observed during the treatment. The decline of HBV DNA at week 24 and HBe Ag at week 12, 24 predicted a combined response at week 48. A decrease of 3.43log10copies/m L in serum HBV DNA at week 24 had high negative predictive(94.55%) value. During treatment, serum HBe Ag levels decrease of 0.67 and 1.06log10s/co at weeks 12 and 24 of therapy, respectively, had high predictive values of combined response(negative predictive value 42.86%, positive predictive value 90.00%, the area under the receiver operating characteristic curve 0.772 for week 12; negative predictive value 45.00%, positive predictive value 94.44%, the area under the receiver operating characteristic curve 0.844 for week 24). Cox multi-factor analysis showed that the levels of HBV DNA and the decrease of HBe Ag at week 24 were predictive factors for combined response at the end of therapy.Conclusions: For HBeAg positive CHB patients who did not achieved early virological response, combing with adefovir dipivoxil can improve the combined response, the rate of ALT normalization and HBV DNA negative. The decrease of serum HBV DNA at week 12, HBe Ag at week 12 and 24 can provide evidence whether discontinued the therapy or not for HBe Ag positive CHB patients who achieving Peg-IFN α had poor virological response. The level of serum HBVDNA and the decrease of serum HBe Ag at week 24 may be useful tools to predict the combine response in these patients.