拉米夫定治疗HBeAg阳性慢性乙型肝炎患者血清转换持久性的研究

目的观察拉米夫定长期治疗慢性乙型肝炎(CHB)3年以上患者的血清转换率和停药后持久率,及影响疗效的有关因素.方法167例CHB患者,每天服用拉米夫定100mg,持续3年以上,连续2次以上出现血清转换(间隔3个月),即HBeAg转阴和抗HBe转阳,继续服药6～12个月后,停药并随访1年以上.服药第1年每月,以后第3个月观察临床症状和血清病毒学标志、丙氨酸转氨酶(ALT)、HBV DNA定量及YMDD变异等项目.HBV基因分型应用型特异性PCR方法.结果共有45例患者出现血清转换(27.0%),继续服药6～12个月后停药并随访1年以上,9例出现血清学重新激活,血清转换持久率为80.0%.经单因素统计和Logistic多元回归分析,得出血清转换率和停药后持久率与基线ALT水平呈正相关,与基线HBV DNA水平和治疗后YMDD变异呈负相关.结论CHB患者出现血清转换后继续应用拉米夫定治疗6个月以上,大多数患者可达到持续转换.对血清转换率和持久率有显著影响意义的因子为基线ALT、治疗后YMDD变异.

Durability of seroconversion after long-term lamivudine therapy in HBeAg positive chronic hepatitis B patients

Objective To observe the factors of which may impact the rate of HBeAg seroconversion and its durability after long-term lamivudine therapy in patients with HBeAg positive chronic hepatitis B. Methods 167 patients with HBeAg positive CHB were treated with lamivudine 100 mg daily more than 3 years.Once HBeAg seroconversion occurred more than two times(once every 3 months),the patients continued for 6-12 months,then stopped lamivudine and were followed-up for more than 1 year.The clinical,virological and biochemical observation and tests were performed monthly in the first year,then every 3 months.HBV serologic markers,HBV DNA level,alanine aminotransferase (ALT),and YMDD mutation were tested.HBV genotyping was performed by type-specific PCR.Data were analyzed by Logistic multivariant analysis.Results 45 patients obtained HBeAg sreoconversion(27.0%).The annual accumulative seroconversion rates were 10.2%,16.7%,23.3%,25.1%and 27.0% in 1st,2nd,3rd,4th and 5th years,respectively.9 patients developed reactivation with reappearance of HBeAg and elevation of HBV DNA after more than 1 year followed-up.The 1-year durability of HBeAg seroconversion after discontinuing lamivudine therapy was 80.0%.The single and multivariate analysis showed that the rate of HBeAg seroconversion and its durability were positively corrlated with a high baseline ALT,negatively correlated with a high baseline HBV DNA and YMDD mutation.Conclusion Continuation of lamivudine therapy for more than 6 months after HBeAg seroconversion might increase the durability of response.