The Clinic Study Of Adefovir Dipivoxil In Treating Patients With Chronic Hepatitis B And The Relationship Between HBV Genotypes And Its Efficacy

Objective: The aim to this randomized multicenter, double-blind, placebo-controlled clinic study is to determine the efficacy and safety of adefovir dipivoxil made in RuiGuang company in treating patients with chronic hepatitis B.Methods: This was a randomized eleven centers, double-blind, placebo-Controlled 48 weeks of clinic study of adefovir dipivoxil(ADV). 240 patients were studied in eleven centers, 24 patients were enrolled in our center. 24 patients were randomized to receive 10 mg adefovir dipivoxil per day(4 patients in GroupA,12 patients in Group B) or placebo(8 patients in Group C) for 12 weeks. During the following 24 weeks all of the 24 patients received 10 mg adefovir dipivoxil per day. During the last 12 weeks, the patients in Group A received placebo and the patients in Group B and C received 10 mg adefovir dipivoxil per day. Medicine received in Group A, B, C was described in the table below. The efficacy of adefovir dipivoxil was assessed by the change of HBV DNA and ALT level of serum and hepatitis B serology markers, and the safety of adefovir dipivoxil was evaluated by analysis of the type and severity of adverse events in our center and eleven centers. We will described the results of our center only, and the statistics results would be studied in eleven centers.Results: 24 cases were observed in our study, 2 cases were shedding. 240 cases were observed in eleven centers, 13 cases were shedding, 6 cases were eliminated.At the week 12, HBV DNA levels droped obviously from baseline HBV DNA in Group A and B. A decline of at least 21og₁₀ from baseline HBV DNA, undetectable HBV DNA and normalization of ALT levels were 4/4, 2/4, 2/4 in Group A, 9/12, 1/12, 5/12 in Group B, all more than 1/8, 0/8, 1/8 in Group C in our center. A decline of at least 21og₁₀ from baseline HBV DNA and undetectable HBV DNA were 82.50%, 17.50% in Group A, 75.83%, 25.83% in Group B, both more than 15.00%, 1.25% in Group C in eleven centers, and there were significant difference between Group A, B and C(P＜0.01, respectively). Normalization of ALT levels were 37.84% and 45.71% in Group A and B,both more than 20.59% in Group C in eleven centers, and there was significant difference between Group B and C (P＜0.01), but there was no significant difference between Group A and C (P=0.11). This showed adefovir dipivoxil was effective in dropping HBV DNA and normalizeing ALT levels.At the week 36, HBV DNA levels dropped obviously from baseline HBV DNA in Group A, B and C. A decline of at least 21og₁₀ from baseline HBV DNA, undetectable HBV DNA and normalization of ALT levels were 4/4, 3/4, 3/4 in Group A, 10/12, 4/12, 9/12 in Group B, 7/8, 1/8, 3/8 in Group C in our center. A decline of at least 21og₁₀ from baseline HBV DNA, undetectable HBV DNA and normalization of ALT levels were 85.00%, 37.50%, 75.68% in Group A, 85.00%, 26.67%, 67.62% in Group B, 78.75%, 28.75%, 52.94% in Group C in eleven centers, and they were all no significant difference among the three groups(A, B, C) in eleven centers (P＞0.05, respectively). This showed after the patients in Group C received 10 mg adefovir dipivoxil per day, HBV DNA levels began to drop and normalization of ALT levels raised.At the week 48, HBV DNA levels droped obviously from baseline HBV DNA in Group B and Group C, but there was a relapse of HBV DNA in Group A. A decline of at least 21og₁₀ from baseline HBV DNA, undetectable HBV DNA, the rate of ALT levels normalization were 9/12, 4/12, 7/12 in Group B, 6/8, 1/8, 4/8 in Group C, all more than 2/4, 0/4, 1/4 in Group A in our center. A decline of at least 21og10 from baseline HBV DNA, undetectable HBV DNA and normalization of ALT levels were 82.50%, 34.17%, 72.38% in Group B, 80.00%, 31.25%, 60.29% in Group C, all more than 32.50%, 7.50%, 27.03% in Group A in eleven centers, and they were all significant difference between Group B, C and A in eleven centers(P＜0.01, respectively). This showed HBV DNA levels could drop always if continuing received adefovir dipivoxil, and there would have a relapse after withdrawing adefovir dipivoxil early.Debility, nausea, bellyache, diarrhea, dyspepsia were abserved in our center. The adverse effect was minor, and there was no serious adverse event and renal function damage related to adefovir dipivoxil.Conclusion: Adefovir dipivoxil made in RuiGuang company is effective in dropping HBV DNA and normalizeing ALT levels and safe in treating patients with chronic hepatitis B. Objective: To study the relationship between the HBV genotypes and the efficacy of adefovir dipvoxil in treating patients with chronic hepatitis B.Methods: 41 patients with chronic hepatitis B, who were treated by adefovir dipivoxil 10mg per day for 48 weeks, were selected by expectation. To extract the HBV DNA from the patients blood serum. The surface genes of hepatitis B viruses were amplified by the polymerase chain reaction and sequenced. The relationship of these new S gene sequences to those of the published previously was investigated by constructing a phylogenetic tree, which classified these new S gene sequences into different groups, so it could determine the HBV genotypes.Results: 41 cases were studied, 25 cases were HBV genotype B and 16 cases were HBV genotype C. At the week 12, 24, 36 and 48, there is no significant difference in virological response and biochemical response between genotype B and C. At the week 48, a decline of at least 21og₁₀ from baseline HBV DNA was 60.9% (14/23) and 71.4% (10/14) in HBV genotype B and C, the difference is not significant. HBV DNA below the detection limit of 10³ copies/ml was 43.5 % (10/23) and 42.9% (6/14) in HBV genotype B and C, the difference is not significant. Normalization of ALT levels was 60.9% (14/23) and 71.4% (10/14) in HBV genotype B and C, the difference is not significant. HBeAg nagative and HBeAg seroconversion were 29.2% (7/24) and 8.3% (2/24) in genotype B, 33.3% (5/15) and 20% (3/15) in genotype C, the difference is not significant.Conclusion: There is no conspicuous association between HBV genotype B, C and the efficancy of adefovir dipivoxil in treating patients with chronic hepatitis B.