阿德福韦酯治疗乙型肝炎肝硬化失代偿期患者96周的临床观察

A clinical study of adefovir dipivoxil treatment for chronic hepatitis patients with cirrhosis in their decompensation period

目的研究阿德福韦酯和拉米夫定治疗乙型肝炎肝硬化失代偿期患者96周的疗效和不良反应。方法乙型肝炎肝硬化失代偿期患者随机分为阿德福韦酯组和拉米夫定组，分别口服阿德福韦酯10mg／d和拉米夫定100mg／d，并均给予常规护肝及对症、支持治疗，疗程96周。观察48、72、96周时，两组患者的肝功能、HBeAg、HBVDNA、肝纤维化指标、病毒耐药突变率、Child—Pugh分级及并发症情况。两组问均数比较采用f检验，多组问均数比较采用方差分析，计数资料比较采用x^2检验。结果治疗48周时，ALT、AST、白蛋白及总胆红素复常率，阿德福韦酯组分别为82．8％、86．2％、37．9％和82．8％，拉米夫定组分别为71．4％、85．7％、50．0％和75．0％，但两组间差异无统计学意义（x^2值分别为0．495、0．107、0．424和0．155，P值均〉0．05），且随着疗程的延长，患者肝功能指标复常率无明显变化。治疗48周时，两组患者的HBVDNA水平均较治疗前明显下降（f值分别为19．298和20．787，尸值均〈0．01），但差异无统计学意义（P〉0．05）。随着疗程的延长，阿德福韦酯组HBVDNA水平不断降低（F=6．34，P〈0．01），拉米夫定组无明显差异（F=1．10，P〉0．05）。患者血清HBeAg转阴率及HBeAg／抗HBe转换率随着治疗疗程的延长均增加，但两组间差异无统计学意义。96周时的病毒耐药突变率，拉米夫定组为25．0％，明显高于阿德福韦酯组的3．4％（x^2=3．843，P〈0．05）。两组患者血清肝纤维化指标随着疗程的延长均维持较低水平，Child-Pugh分级在治疗至96周时均有所提高。治疗中的并发症发生率，阿德福韦酯组34．5％，拉米夫定组为28．6％，差异无统计学意义（x^2=0．038，P〉0．05）。结论阿德福韦酯对乙型肝炎肝硬化失代偿期患者的抗病毒疗效与安全性好，病毒耐药突变率低。

Objective To evaluate the efficacy and safety of 96 weeks adefovir dipivoxil （ADV） treatment for chronic hepatitis patients with cirrhosis in their decompensation period. Methods Chronic hepatitis patients with cirrhosis in their decompensation period were randomly divided into two groups. An ADV group： patients treated with 10 mg ADV per day; a lamivudine （LMV） group： patients treated with 100mg LMV per day. The course of treatment lasted 96 weeks. Serum levels ofALT, AST, Alb, Tbil, HbeAg, HBV DNA, PCIII, IVC, LN and HA, renal function, Child-Pugh scores, drug adverse reactions and complication during the treatment of the two groups were analyzed. Results During the two-year treatment, the proportions of patients with a return to normal liver function were similar in both groups. With the treatment prolonged, serum HBV DNA levels of the patients in adefovir dipivoxil group decreased gradually. The HBV DNA level in some lamivudine-treated patients was increased. The sero-conversion rate of HBeAg/HBeAb of the patients in the two groups was increased with the prolongation of the treatment. At 96 weeks, the ratio of emerging virus-resistant strains was lower in the adefovir dipivoxil group than in the lamivudine group. The levels of the serum markers of hepatic fibrosis of the patients in the two groups remained low. Child-Pugh scores of the patients in the two groups were significantly improved. No significant difference in the total incidence of complications between the two groups was noticed. Each of the two groups had a patient with liver-kidney syndrome and other serious complications. Conclusion The efficacy and safety of adefovir dipivoxil and lamivudine treatment for the above patients are similar, but the ratio of emerging virus-resistant strains of the adefovir dipivoxil treatment group is lower than that of lamivudine treatment group.