Clinical Study Of Adefovir Dipivoxil For Treatment Of HBeAg Positive Patients With Chronic Hepatitis B

[Objective] To observe the efficacy of naive Adefovir dipivoxil (ADV) treatment for HBeAg positive patients with chronic hepatitis B, evaluate the difference between Adefovir dipivoxil and Lamivudine (LAM) combined therapy and Adefovir dipivoxil monotherapy for HBeAg positive LAM-resistant patients with chronic hepatitis B, and compare the emergence of the ADV-resistance mutations among patients in three groups in 48 weeks.[Methods] 90 patients with chronic hepatitis B who were positive for HBeAg were selected for this study. 30 patients in group A were treated with Adefovir dipivoxil monotherapy for the first time for 48 weeks. 60 patients with Lamivudine-resisitance who were positive for HBeAg were ramdomly put into group B and C. In group B 30 patients were treated with Adefovir dipivoxil and lamivudine combined therapy for 48 weeks, while 30 patients in group C were treated with Adefovir dipivoxil and Lamivudine combined therapy for 12 weeks and Adefovir dipivoxil monotherapy for 36 weeks. All baseline, 12- week, 24-week, 36 -week and 48-week blood samples were analyzed for HBV DNA, HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc,Alanine aminotransferase(ALT). 48-week blood samples were analyzed for ADV-resistant mutation by DNA sequencing method. The primary checking criterion was the serum HBV DNA change during the treatment. The secondary ones were ALT normolization, HBeAg loss and HBeAg seroconversion. [Results]1. Group A: after being treated with Adefovir dipivoxil monotherapy for 48 weeks, ALT normalization rate was 76.67%. The serum HBV DNA negative rate was 53.33%, and median serum HBV DNA level was reduced 4.23±2.30 log 10copies/ml. The HBeAg negative rate was 36.67%, and 5 patients developed seroconversion. 5 of 30 patients developed complete response and 25 of 30 patients developed incomplete response respectively. No ADV-resistant mutation was detected in group A at 48 weeks.2. Group B: after being treated with Adefovir dipivoxil and Lamivudine combined therapy for 48 weeks, ALT normalization rate was 80 %. HBV DNA negative rate was 56.67% and median serum HBV DNA level was reduced 4. 33±1.10 log 10copies/ml. HBeAg negative rate was 33.33%, and 5 patients developed seroconversion. 5 of 30 patients developed complete response and 21 of 30 patients developed incomplete responce respectively. No ADV-resistant mutation was detected in group B at 48 weeks.3. Group C: after being treated with Adefovir dipivoxil and Lamivudine combined therapy for 12 weeks and Adefovir dipivoxil monotherapy for 36 weeks. ALT normalization rate was 50%. HBV DNA negative rate was 30% and medianserum HBV DNA level was reduced 2.86±0.90 log 10copies/ml. HBeAg negative rate was 16.67%, and 2 patients developed seroconversion. 2 of 30 patients developed complete responce and 15 of 30 patients developed incomplete response respectively. 2 patients developed ADV-resistant rtA181T mutation in group C at 48 weeks. [Conclusion]1. For HBeAg positive patients with chronic hepatitis B, 48 weeks naive Adefovir dipivoxil monotherapy resulted in good virological and biochemical improvements.2. For Lamivudine-resistant HBeAg positive patients with chronic hepatitis B, 48 weeks Adefovir dipivoxil and lamivudine combined therapy resulted in virological and biochemical improvements compared with Adefovir dipivoxil monotherapy. 6.67% of Lamivudine-resistant patients developed ADV-resistant mutation after been treated with Adefovir dipivoxil monotherapy in group C at 48 weeks.3. HBeAg seroconersion rate of all three groups was relatively low at 48 weeks, so oral antiviral therapy needs longer duration.