A Clinical Study Of Adefovir Dipivoxil (ADV) For The Treatment Of Hepatitis B E Antigen-Positive Chronic Hepatitis B

Background Chronic hepatitis B virus (HBV) infection is a wordwide problem. The number of individuals infected with this virus has been estimated to be as high as 350 million. The annual global mortality associated with persistent HBV infection is about 1.2million. Most deaths are attributable to complications of cirrhosis and the development of hepatocelluar carcinoma. Adefovir Dipivoxil (ADV), a nucleotide analogue, demonstrated clinically siginificant antiviral activity in patients with chronic hepatitis B and proven to treat chronic hepatitis B by FDA.Objective To acess the efficacy and safety of long term of ADV for treatement of hepatitis e antigen positive Chinese patients with chronic hepatitis B.Methods We randomly assigned 48 patients with chronic hepatitis B who were positive for hepatitis B e antigen to receive 10 mg of Adefovir Dipivoxil (group A; 36 patients ) or placebo (group B ; 12 patients) daily for 12 weeks in a double-blind manner. Then all patients received 10 mg of Adefovir Dipivoxil to the 40th week .The patients of group A were secondly assigned to receive 10 mg of Adefovir Dipivoxil (group A1) or placebo (group A2) daily to the 52th week in a 1:1 ratio and a double-blind manner .The group B followed the treatment with ADV . After 52 weeks of treatment ,all patients received ADV 10 mg daily for 52 weeks.Resuls At week 12, Alanine aminotransferase declined from 226.69±185.63 U/L (P=0.000), HBVDNA levels had declined 3.77+1.041og₁0 (P=0.000), hepatitis B e antigen quantitatives declined from 701.08 + 419.02 S/CO to 287.69±422.89 S/CO but has not statistical significance (P=0.60) in group A; In group B, the parameterswere similar to that of base-line. Alanine aminotransferase levels had normalized in 58.33 percent of patients at week 40 and in 85.42 percent of patients at week 104 respectively; 27.08 percent of patients and 58.33 percent of patients had no detectable serum HBVDNA at week 40 and week 104 respectively; Hepatitis B e antigen loss rates are 16.67 percent and 27.08 percent at week 40 and week 104 respectively. All patients in group A2 had ALT and HBVDNA levels breakthrough. The safety profile of the 10 mg dose of Adefovir Dipivoxil was similar to that of placebo. There was no renal laboratory abnormalities in all patients.Conclusion In patients with HBeAg-positive chronic hepatitis B, 104 weeks treatment of Adefovir Dipivoxil 10 mg per day resulted in significant virological and biochemical improvement, and with the safety profile similar to that of placebo. After 40 weeks of ADV treatment, drug stopping can result in ALT increase and HBVDNA relapse, and may lead to disease breakthrough.