拉米夫定联合日达仙治疗慢性乙型肝炎患者三年随访研究

A Long-term Observation and Follow-up for Patients with Chronic Hepatitis B after Treatment of Lamivudine with ZADAXIN(thymosinα1)

目的观察拉米夫定(LAM)和日达仙(ZADAX IN,Tα1)联合治疗慢性乙型肝炎的长期疗效和安全性。方法选择50例HBV-DNA、HBeAg阳性的慢性乙型肝炎患者,按成组配对原则分为两组,拉米夫定治疗组(LAM组)和联合治疗组(LAM+Tα1组),每组各25例。结果治疗1年时,LAM+Tα1组HBeAg血清转换率为45.8%明显高于LAM组9.5%(P<0.01);LAM+Tα1组HBV-DNA阴转率、ALT复常率和YMDD变异发生率分别为83.3%,91.7%,0,LAM组HBV-DNA阴转率、ALT复常率和YMDD变异发生率分别为61.9%,90.5%,4.8%(P>0.05)。治疗2年时LAM+Tα1组HBeAg血清转换率、HBV-DNA阴转率、ALT复常率和YMDD变异发生率分别为62.5%,79.2%,83.3%和8.3%;LAM组分别为28.6%,47.6%,52.4%和33.3%(P<0.05)。治疗3年时LAM+Tα1组HBeAg血清转换率、HBV-DNA阴转率、ALT复常率和YMDD变异发生率分别为45.8%,62.5%,70.8%和16.7%;LAM组分别为14.3%,23.8%,38.1%和52.4%(P<0.05;P<0.01)。治疗1、2和3年后LAM+Tα1组的完全应答率分别为45.8%,58.3%和41.7%明显高于LAM组的9.5%,28.6%和14.3%(P<0.05;P<0.01);两组部分应答率无明显差异(P>0.05)。LAM+Tα1组中1例出现一过性轻度血清淀粉酶升高,LAM组中1例出现皮疹,其余均未出现无明显的不良反应。结论拉米夫定与日达仙联合治疗慢性乙型肝炎,疗效优于单一用药组,且非常安全。

OBJECTIVE Current treatments for chronic hepatitis B are suboptimal. In the search for improved therapies, we compared the long-term efficacy and safety of Lamivudine （LAM） plus thymosin α1 （ZADAXIN, Tα1） with lamivudine alone for the patients with chronic hepatitis B. METHODS 50 patients with HBeAg-positive chronic hepatitis B was divided into two groups,and received either Lamivudine （ 100mg daily ） plus Tα1 （ 1.6 mg twice weekly ） or Lamivudine alone. Patients were treated for 2 years and followed by an additional one year. RESULTS 45.8 percent of the patients achieved HBeAg seroconversion in combination group while 9.5 percent of the patients in LAM group achieved HBeAg seroconversion at the first year（ P 〈 0.01 ）, however,HBV DNA lead and ALT levels decreased rapidly in two groups（ P 〉 0. 05 ）. After 2 years follow-up, the patients received Tctl plus lamivudine got higher HBeAg seroconversion than those received lamivudine monotherapy [ 62.5 percent vs. 28.6 percent （ P 〈 0. 05 ） and 45.8 percent vs. 14.3 percent （ P 〈0.05 ）, respectively]. The ALT normalization was 83.3 percent vs. 52.4 percent （ P 〈0. 05 ） and 70. 8 percent vs. 38.1 percent （ P 〈0. 05 ）, respectively. And the HBV DNA levels below 1 000 copies per milliliter was 79.2 percent vs. 47.6 percent （P〈0.05） and 62.5 percent vs. 23.8 percent （P〈0.01）, respectively. In the meantime, the patients received Tctl plus lamivudine had less than those YMDD mutant received lamivudine monotherapy [ 8.3 percent vs. 33.3 percent （ P 〈 0. 05 ） and 16.7percent vs. 52.4 percent （P 〈0.05）, respectively]. 45.8 percent of patients receiving Tctl plus lamivudine achieved complete response, as compared with 9.5 percent in the group receiving lamivudine alone at the first year, and the sustained response rates were 58.3% and 41.7% vs. 28.6% and 14.3%, respectively （ P 〈 0.01 ）. No serious adverse events were recorded in the two groups. CONCLUSION In patients with HBeAg-positive chronic hepatitis B, Lamlvudine plus thymosinctl offers superior efficacy over lamivudine alone, on the basis of HBeAg seroconversion, HBV DNA suppression, ALT normalization and YMDD mutant.