恩替卡韦治疗104例乙型肝炎肝硬化患者96周的疗效观察

Antiviral effects of entecavir in patients with hepatitis B virus-related cirrhosis

目的观察恩替卡韦治疗乙型肝炎肝硬化的临床疗效。方法随机选择就诊于长春市中日联谊医院消化内科未经过抗病毒治疗的乙型肝炎肝硬化患者104例，给予恩替卡韦0．5mg，每日1次口服，连续口服96周时总结临床疗效。观察患者治疗前、后血清HBV DNA水平、肝功能及HBV标志物，其中37例患者治疗前及治疗96周后行肝组织学检查。率的比较采用Х^2检验，相关性分析采用Pearson相关系数。结果恩替卡韦治疗4周时，HBV DNA水平平均下降3．1log10，至96周时平均下降幅度达到5．1log10，HBVDNA不可测率达到98．1％，ALT复常率达到80．7％；72例HBeAg阳性患者96周时HBeAg／抗HBe血清转换率为13．9％。104例乙型肝炎肝硬化患者中，C基因型HBV感染者64例，占61．5％，B基因型28例，占26．9％。不同基因型HBV感染者患者接受恩替卡韦治疗后的HBV DNA不可测率、ALT复常率以及HBeAg血清转换率差异无统计学意义。Child-Pugh C级2例（2／21，9．5％），Child—Pugh B级1例（1／52，1．9％）出现疾病进展，Child—Pugh A级患者31例，未出现疾病进展。37例行肝组织学检查的乙型肝炎肝硬化患者治疗96周时，肝组织学改善者ChildPughA级17例（17／21，81．0％），B级6例（6／9，66．7％），C级3例（3／7，42．9％）。治疗前HBVDNA水平越高，Knodell HAI评分越高，r=0．80。抗病毒治疗96周后血清HBVDNA下降水平与Knodell HAI评分下降水平仍呈正相关，r=0．93。结论恩替卡韦抗病毒治疗乙型肝炎肝硬化患者疗效显著，可延缓及阻止肝硬化患者的疾病进展。

Objective To analyze antiviral effects of entecavir in patients with hepatitis B virusrelated cirrhosis. Method 104 patients of hepatitis B virus-related cirrhosis with no previous history of antiviral therapy were treated with entecavir 0.5 mg once daily. 37 patients were taken hepatic histologic examination before and after the treatment. Results Mean reductions of serum HBV DNA was 5.1 log10 96 weeks after the treatment, HBV DNA became undetectable in 98.1% patients, and ALT became normal in 80.7% patients; HBeAg seroconversion occurred in 13.9% of the 72 HBeAg positive patients; 61.5% of these patients were infected with genotype C HBV, and 26.9% were infected with genotype B HBV. The genotype of HBV was not assocaited with the therapeutical effect. Child-pugh score was assocatied with the progression of the disease： the proportion of patients with disease progression was highest in Child-Pugh C grade patients and lowest in Child-Pugh A grade patients. The level of the HBV DNA load was positively correlated with Knodell HA1 score at the baseline and 96 weeks after the treatment. Conclusion Entecavir treatment results in suppression of HBV replication and delayed progression of fibrosis in patients with hepatitis B virusrelated cirrhosis.