经拉米夫定治疗后慢性乙肝患者停药变化的规律研究

Follow-up patients with chronic hepatitis B after withdrawal of lamivudine

目的拉米夫定(贺普丁)是一种核苷类似物,对于慢性乙肝患者的治疗已经显示其治疗的有效性;但尚缺乏拉米夫定治疗的慢性乙肝患者在撤药后的长期疗效观察.本文旨在研究其治疗慢性乙肝疗效稳定性及变化规律.方法所有病例均为1999年10月至2001年2月四川大学华西医院、四川省人民医院的门诊或住院患者.慢性乙肝患者治疗初均符合以下标准:HBsAg(+);HBeAg(+);80IU/L≤ALT≤600IU/L并经过拉米夫定100mg/d,口服,疗程1.0～1.5年.每3个月检测肝功能、乙肝病毒血清学标记物(HBVm)、血HBV DNA、血常规等.疗效判断:完全反应,HBV DNA转阴,ALT正常,HBeAg/抗HBeAg血清转换;部分反应,HBV DNA转阴,ALT正常,HBeAg/抗HBeAg未转换;复发,HBV DNA转阳,ALT异常,和/或HBeAg(+);无反应,HBV DNA(+),HBeAg(+),ALT/AST(↑).血HBV DNA定量检测用AB5700定量PCR仪采用基于Taqman技术的荧光定量PCR系统.随访时间2年.结果纳入观察的慢性乙肝患者105例,完全反应15例,部分反应28例,无效62例.15例完全反应患者随访期间,5例出现复发,持续完全反应率降至 66.7% ;其中2例出现血清学转换,持续完全反应率稳定在80%,未观察到病情加重者.28例部分反应患者停药先后16例出现复发,其中5例患者出现病情加重;2例患者出现血清学转换,以后持续反应率稳定在50%.无效患者随访期间,无病情加重者,可以观察到自发的血清转换.女性比男性患者的疗效更为稳定(分别为78.9%,50%, P ＜0.05).结论经过拉米夫定治疗有效的患者中,以完全反应患者的疗效为稳定;部分反应患者出现复发时间更早,并可能出现病情加重.慢性乙肝患者经拉米夫定治疗的有效患者中,女性比男性稳定.

Objective Chronic hepatitis B virus （HBV） infection is a common infectious disease .Lamivudine is a nucleoside analogue with potent inhibitory effects on HBV polymerase/reverse transcriptase activity. It is not clear the changes of patients with chronic hepatitis B （CHB） after lamivudine treated. We aim to follow up these patients to elucidate it. Methods All patients with CHB at initial stage should have serum HBsAg positive, HBeAg positive, HBV DNA positive, elevated alanine aminotransferase （ALT） between 80 to 600 IU/L and had been given lamivudine 100mg daily for 1.0～1.5 years .The criteria for complete response （CR） includes serum HBV DNA negative, ALT normal, HBeAg/Anti-HBeAg seroconversion, partly response （ PR ） includes serum HBV DNA negative, ALT normal, HBeAg negative and Anti-HBeAg negative,no response （NR） includes no improve above mentioned. Relapse serum HBV DNA positive, serum ALT elevated,and HBeAg positive or negative. They were followed up 24 months and every 3 months given testing markers above mentioned. Results Among 105 cases with CHB,15 eases had CR,28 cases had PR,and 62 cases had NR.In CR group,5 cases relapsed;Among them,2 cases had spontaneous seroconversion,only 3 cases left;sustained CR rate was 80% .In PR group, total 16 cases had relapsed. Among them,2 cases had spontaneous seroconversion,5 cases became aggravation, and sustained PR rate was 50% （P〈0.05） . In NR group,we observed cases with spontaneous seroconversion. Among 43 cases with CR or PR,the sustained CR or PR rate in 19 females was 78.9%, the rate in 24 males was 50% （P〈0.05） .Conclusion Patients with CR had more stability compare with patients with PR and later had risk for become aggravation after withdrawal of lamivudine. Females with CR or PR had more sustained rates than males.