HBeAg阴性的肝硬化抗病毒治疗的疗效观察

摘要

Objective To investigate the efficacy of nucleot (s)ide analogues therapy in patients with HBeAg-negative cirrhosis in China. Methods 111 patiens with HBeAg-negative cirrhosis were divided into antiviral group (58 cases, 25 entecavir, 19 adefovir dipivoxil, 13 lamivudine, 1 telbivudine) and control group (53 cases, supportive and symptomatic treatment). These two groups were matched for demography, liver function and Child-Push score. Results At the 96th week, the rate of ALT normalization and HBV DNA drop (lg copies/ml) in antiviral group were higher than those in control group(P<0.05). The rates of HBV DNA negative (< 500copies/ml) were 88.7% (47/53) and 32.5% (13/40) , respectively (P < 0.05). There were no differences in the rates of developing HCC and undergoing variceal bleeding between antiviral group and control group (P>0.05 ). 15.4% patients with lamivudine treatment emerged YMDD mutations. 10.5% patients with adefovir dipivoxil treatment emerged virologic breakthrough and hepatitis flare during the second year. 2 patients (3.5%) in treatment group and 6 patients (11.5%) in control group died of liver failure or variceal bleeding or HCC (P>0.05). Conclusions Neucleot (s) ide analogues are effective in suppressing HBV replication in patients with HBeAg-negative cirrhosis, but the impact of which on the mortality and complications of cirrhosis should be prolongly observed. For continuing treatment, the neucleot(s) ide analogues with strong effective and low resistance are the first choices to prevent viral mutation and drug resistance.%目的 观察核苷类药物对HBeAg阴性的乙型肝炎肝硬化患者的抗病毒疗效.方法 采用队列研究,将111例患者分为治疗组58例和对照组53例,两组患者的人口学、肝功能及Child-Pugh评分相当.治疗组在常规治疗的基础上加用核苷类药物抗病毒治疗,其中恩替卡韦25例、阿德福韦酯19例、拉米夫定13例、替比夫定1例;对照组给予支持对症治疗.结果 随访96周后,治疗组的ALT复常率和HBV DNA下降幅度均高于对照组(P<0.05).两者的HBV DNA转阴率(<500拷贝/ml)分别为88.7%(47/53)及32.5%(13/40),差异有统计学意义(P<0.05).13例拉米夫定治疗者中,有2例出现YMDD变异;19例阿德福韦酯治疗者中,有2例在第二年出现病毒学突破和肝炎发作.两组的原发性肝细胞癌和消化道出血的发生率比较差异无统计学意义(P>0.05).治疗组共有2例(3.5%)死亡,对照组6例(11.5%)死亡,两组病死率比较差异无统计学意义(P>0.05).结论 核苷类药物对HBeAg阴性的肝硬化能有效抑制HBV复制,但对降低消化道出血及肝癌的发生及病死率还需要进一步观察.避免病毒变异和耐药,应首选强效和低耐药的核苷类药物.