两种恩替卡韦片剂治疗慢性乙型肝炎患者的肝纤维化动态观察

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目的评价慢性乙型肝炎(CHB)患者接受抗病毒治疗后肝纤维化指标的变化。方法选择2008年10月至2014年4月接受马来酸恩替卡韦或者恩替卡韦治疗的CHB患者作为研究对象。患者随机分为两组,A组给予0.5 mg/d恩替卡韦片,B组给予0.5 mg/d马来酸恩替卡韦片治疗,共48周。此后所有患者均给予0.5 mg/d马来酸恩替卡韦片治疗,共24周。于基线和治疗72周后进行透明质酸(HA)、肝纤维化指数(Fibroindex)、血清HBV标志物检测和分析,比较两组肝纤维化的变化情况。结果共184例患者纳入,男134例(72.8%),女50例(27.2%),HBe Ag阳性146例(79.3%)。A组和B组基线血清HBV DNA分别为7.7(6.5,8.2)log10IU/ml,7.6(6.5,8.2)log10IU/ml(Z=0.078,P=0.938);72周HBV DNA分别为1.3(1.3,1.9)log10IU/ml和1.3(1.3,2.1)log10IU/ml(Z=0.066,P=0.947),组内前后比较差异均有统计学意义(P<0.001)。A、B组基线HA分别为37.4(20.7,55.0)μg/L和34.0(22.2,56.5)μg/L(Z=0.161,P=0.872);72周时HA分别为24.7(17.9,36.6)μg/L和25.8(20.0,35.1)μg/L(Z=0.519,P=0.603),组内前后比较差异均有统计学意义(P<0.001)。A、B组基线Fibroindex分别为1.7(0.6,3.6)和1.7(0.6,4.1)(Z=0.073,P=0.941);72周时Fibroindex分别为0.5(0.2,1.1)和0.5(0.1,1.2)(Z=0.143,P=0.887),组内前后比较差异均有统计学意义(P<0.001)。基线和72周Fibroindex均与基线体重和年龄呈正相关(P<0.05),与性别、基线HBV DNA、基线HBe Ag状态呈负相关(P<0.05)。结论马来酸恩替卡韦和恩替卡韦治疗CHB患者可降低血清HBV DNA水平,还可使血清HA和Fibroindex指数较快下降,改善肝纤维化。男性、基线体重大、基线年龄大、基线HBe Ag阴性、基线HBV DNA低者的肝纤维化较重。 Objective To evaluate the changes of liver fibrosis indexes in patients with chronic hepatitis B (CHB) receiving antiviral therapy. Methods CHB patients treated with entecavir maleate or entecavir from October 2008 to April 2014 were selected as the study subjects. Patients were randomized into two groups: 0.5 mg / d entecavir in group A and 0.5 mg / d entecavir maleate in group B for 48 weeks. All patients were then given 0.5 mg / day entecavir maleate for 24 weeks. At baseline and 72 weeks after treatment, HA, Fibroindex and serum HBV markers were detected and analyzed. The changes of liver fibrosis were compared between the two groups. Results A total of 184 patients were included, 134 (72.8%) were male, 50 (27.2%) were female, and 146 (79.3%) were positive for HBeAg. The baseline serum HBV DNA of group A and group B were 7.7 (6.5,8.2) log10 IU / ml and 7.6 (6.5,8.2) log10 IU / ml respectively (Z = 0.078, P = 0.938) 1.9), and the difference was statistically significant before and after treatment (P <0.001). The HA of group A and group B were 37.4 (20.7,55.0) μg / L and 34.0 (22.2,56.5) μg / L respectively (Z = 0.161, P = 0.872) / L and 25.8 (20.0, 35.1) μg / L respectively (Z = 0.519, P = 0.603). There were significant differences between before and after treatment (P <0.001). The Fibroindex of group A and group B were 1.7 (0.6,3.6) and 1.7 (0.6,4.1) respectively (Z = 0.073, P = 0.941). The Fibroindex of group A and group B were 0.5 (0.2,1.1) and 0.5 (Z = 0.143, P = 0.887). There was significant difference between the two groups before and after treatment (P <0.001). Baseline and Fibroindex at 72 weeks were positively correlated with baseline weight and age (P <0.05), and negatively correlated with gender, baseline HBV DNA and baseline HBe Ag status (P <0.05). Conclusion Treatment of patients with CHB with entecavir maleate and entecavir can reduce the level of serum HBV DNA and also decrease the serum HA and Fibroindex index rapidly and improve liver fibrosis. Men, with a large baseline body mass, large baseline age, baseline HBeAg-negative, and severe liver fibrosis with low baseline HBV DNA.
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