拉米夫定治疗慢性乙型肝炎2年临床疗效及病毒的变异

Clinical effect and virus mutation of lamivudine treatment in 2 years trial of chronic hepatitis B

研究拉米夫定治疗慢性乙型肝炎病人 2年的临床疗效。方法 88例病人按 3∶1比例随机分成治疗组和安慰剂组 ,每日服拉米夫定 10 0mg和安慰剂各一片 ,12周以后全部服拉米夫定每日 10 0mg ,持续到 10 4周。定期检测ALT、HBVDNA、HBeAg和抗 HBe。用PCR后直接测序方法检测YMDD变异。结果 75例病人完成 2年试验。 12周时 ,治疗组和安慰剂组HBVDNA阴转分别为 47例 (80 % )和 4例 (2 1% )。 10 4周时 48例 (6 4% )HBVDNA保持阴转。血清转换 19例 (2 5 .33% ) ,8例 (10 .6 6 % )HBeAg已转阴 ,抗 HBe还未转阳。在治疗前ALT值为 <1ULN、>1～ 2ULN、>2～ 5ULN、>5ULN的病人中 ,血清转换率和e抗原转阴率分别为 5例 (13 .15 % )、6例 (33 .33% )、5例 (38.46 % )、3例(5 0 % )和 6例 (15 .78% )、6例 (33 .33% )、11例 (84.6 0 % )、4例 (6 6 .6 6 % )。治疗前和 10 4周时的ALT中位值分别为(71.82 7± 71.6 2 7)U/L和 (34.2 6 7± 31.415 )U/L(P <0 .0 1)。 36例发生YMDD变异 ,总变异率为 48%。变异和非变异者的ALT中位值分别为 (4 5 .0 5 6± 40 .90 3)U/L和 (2 3.6 2 7± 12 .6 9)U/L(P <0 .0 1)。HBVDNA中位值分别为 (2 86 .6 2 5± 482 .877)和 (10 2 .44 8± 380 .2 5 )mEq/ml。血清HBeAg转阴分别为 10和

Objective To evaluate 2 years trial of lamivudine therapy in chronic hepatitis B patients.Methods 88 patients were enrolled and randomized into lamivudine and placebo groups according 3∶1 ratio, they received lamivudine 100mg daily and placebo for 12 weeks respectively. Then all patients were given lamivudine 100mg daily up to 104 weeks. The efficacy and safety were evaluated with clinical, biochemical, hematological and virological parameters. HBV YMDD mutation were assayed by PCR and sequencing methods each year.Results 75 patients completed the study. At the 12 week, 47(80%) of lamivudine treated patients became HBV DNA negative (below 1.6pg/ml) compared with only 4(21%) of those recciving placebo. At the 104 week, the sustained negative patients for HBV DNA were 48(64%). Lamivudine therapy resulted in increased hepatitis B e antigen loss and seroconversion in patients with high baseline serum ALT concentrations. At 2 years loss of HBeAg was achieved by 6(15.78%), 6(33.33%),11(84.60%),4(66.66%) and seroconversion was achieved by 5(13.15%), 6(33.33%), 5(38.46%), 3(50%) of patients with baseline serum ALT concentrations of <1×upper limit of normal (ULN), >1～2ULN, >2～5ULN and 5ULN respectively. Before lamivudine treatment and at the 104 week, the serum ALT median were 71.827±71.625U/L and 34.267±31.415U/L respectively. At 104 week, YMDD mutations developed in 36 patients, the mutation rate was 48%. In YMDD mutation patients and non mutation patients, the serum ALT median were 45.056±40.903U/L and 23.627±12.69U/L respectively ( P <0.01). The HBV DNA median were 286.625± 482.877 mEq/ml(bDNA) and 102.448±380.25mEq/ml respectively. The numbers of loss HBeAg were 10 and 17. The incidence of platelet decrease (below 10×10 9/L×2 times) was 10(13.33%). The other incidence of adverse events were similar to that of the placebo.Conclusion Oral lamivudine effectively suppressed HBV replication, decreased ALT level and improved serum conversion. It was well tolerated, incidence of adverse events was low and partial patients occured YMDD mutation.