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中华实验和临床感染病杂志(电子版)

中华实验和临床感染病杂志(电子版) ›› 2016, Vol. 10 ›› Issue (01) : 31 -35. doi: 10.3877/cma.j.issn.1674-1358.2016.01.007

临床论著

核苷（酸）类药物初始治疗乙型肝炎肝硬化患者的临床疗效比较
阎文昭1, 赵文娟2, 金国华1, 周东方1, 孙慧1, 赵彩彦1,†()   
  1. 1. 050035　石家庄市，河北医科大学第三医院感染科
    2. 050035　石家庄市，河北医科大学第三医院消化科
  • 收稿日期:2015-12-08 出版日期:2016-02-15
  • 通信作者: 赵彩彦
  • 基金资助:
    河北省卫生厅青年科技课题(No. 20100109)

The effect and safety of the different nucleoside analogues for the initial treatment on hepatitis B patients with cirrhosis

Wenzhao Yan1, Wenjuan Zhao2, Guohua Jin1, Dongfang Zhou1, Hui Sun1, Caiyan Zhao1,†()   

  1. 1. Department of Infectious Diseases, The Third Hospital of Hebei Medical University, Shijiazhuang 050035, China
    2. Gastroenterology, The Third Hospital of Hebei Medical University, Shijiazhuang 050035, China
  • Received:2015-12-08 Published:2016-02-15
  • Corresponding author: Caiyan Zhao
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阎文昭, 赵文娟, 金国华, 周东方, 孙慧, 赵彩彦. 核苷（酸）类药物初始治疗乙型肝炎肝硬化患者的临床疗效比较[J]. 中华实验和临床感染病杂志(电子版), 2016, 10(01): 31-35.

Wenzhao Yan, Wenjuan Zhao, Guohua Jin, Dongfang Zhou, Hui Sun, Caiyan Zhao. The effect and safety of the different nucleoside analogues for the initial treatment on hepatitis B patients with cirrhosis[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2016, 10(01): 31-35.

目的

分析不同核苷（酸）类似物初始治疗乙型肝炎肝硬化的临床疗效。

方法

选取2010年8月至2013年8月于河北医科大学第三医院感染科诊断为乙型肝炎肝硬化的患者共218例，随机分为拉米夫定联合阿德福韦酯治疗组（LA组）、替比夫定联合阿德福韦酯组（TA组）、恩替卡韦单药治疗组（EN组）和对照组。分别给予不同抗病毒治疗，持续48周后检测患者相关肝功能以及肝硬化指标并进行综合评价。

结果

经48周的治疗，四组患者的肝功能均有一定程度改善，抗病毒治疗的患者优于对照组，而LA和TA两组联合治疗方式优于EN组单药治疗，差异均有统计学意义（F = 9.775、10.148，P = 0.012、0.008）；四组患者的病毒复制均有所降低，抗病毒治疗的患者优于对照组，而LA组和TA组两组联合治疗方式优于EN组单药治疗，差异均具有统计学意义（F = 11.275、12.198、15.645，P = 0.037、0.016、0.003）；四组患者的肝硬化程度亦有所降低，抗病毒治疗的患者优于对照组，而LA组和TA组两组联合治疗方式优于EN组单药治疗，差异均具有统计学意义（F = 13.534、11.009、12.756，P = 0.015、0.022、0.019）。

结论

使用不同核苷（酸）类似物进行抗病毒治疗后，乙型肝炎肝硬化患者的肝功能以及肝硬化程度有明显改善，且联合用药优于单药治疗。

关键词: 乙型肝炎, 肝硬化, 核苷（酸）类似物, 临床疗效
Objective

To explore the effect and safety of the different nucleos(t)ide analogues for the initial treatment on hepatitis B (HBV) patients with cirrhosis.

Methods

Total of 218 patients diagnosed with HBV with cirrhosis between August 2010 and August 2013 in The Third Hospital of Hebei Medical University were randomly divided into the lamivudine combined with adefovir (LA) group, the telbivudine combined with adefovir (LA) group, entecavir monotherapy (EN) group and the control group. The different antiviral therapy were given among groups for 48 weeks in order to measure the related indexes on the liver cirrhosis.

Results

After the treatment of 48 weeks, the liver function of patients in the four groups were improved to a certain extent, patients with antiviral treatment were better than that of control group, while the liver function of LA group and TA group were superior to the EN group single-agent therapy, with significant differences (F = 9.775, 10.148; P = 0.012, 0.008); the HBV DNA replications were reduced of patients in the four groups, patients with antiviral treatment was better than that of control group, while the reductions of the HBV DNA in LA group and TA group were superior to the EN group single-agent therapy, with significant differences (F = 11.275, 12.198, 15.645; P = 0.037, 0.016, 0.003). The degree of liver cirrhosis of patients in the four groups were improved to a certain extent, patients with antiviral treatment was better than that of control group, while the improvement of the liver’s cirrhosis degree in LA group and TA group were superior to the EN group single-agent therapy, with significant differences (F = 13.534, 11.009, 12.756; P = 0.015, 0.022, 0.019).

Conclusions

The liver function and the degree of cirrhosis improved significantly, and the combination method was superior to the single drug therapy after different nucleotide analogue antiviral treatment.

Key words: Hepatitis B cirrhosis, Nucleos(t)ide analogues, Clinical curative effect
表1 不同联合方案患者的一般情况比较
组别 例数 年龄（岁，±s） 性别（例，男/女） DNA水平（拷贝/ml，±s） Child-Pugh评分（分，±s）
LA组 46 54.2 ± 10.4 30/16 5.2 ± 1.7 7.8 ± 2.5
TA组 32 52.9 ± 8.0 22/10 4.9 ± 1.1 7.8 ± 1.9
EN组 80 53.0 ± 8.2 59/21 5.1 ± 1.2 7.6 ± 1.9
对照组 60 51.0 ± 9.7 42/18 5.0 ± 0.9 8.0 ± 1.2
统计量   F = 0.147 χ2 = 0.217 F = 0.367 F = 1.047
P值   0.821 0.779 0.665 0.209
表2 不同核苷（酸）类似物治疗乙型肝炎肝硬化患者的肝功能改善情况（U/L，±s）
组别 例数 ALT AST
治疗前 治疗后 治疗前 治疗后
LA组 46 135.3 ± 33.4 52.7 ± 9.8 146.3 ± 21.5 59.9 ± 11.1
TA组 32 129.8 ± 29.7 59.7 ± 11.2 143.5 ± 16.8 57.7 ± 10.3
EN组 80 130.5 ± 31.9 73.4 ± 13.2 145.8 ± 12.0 65.7 ± 10.2
对照组 60 131.9 ± 32.7 83.9 ± 12.5 145.7 ± 15.0 89.3 ± 20.6
F值   1.554 9.775 0.975 10.148
P值   0.207 0.012 0.365 0.008
表3 不同核苷类似物治疗乙型肝炎肝硬化患者的病毒复制水平和生化指标（±s）
组别 例数 Child-Pugh评分（分） HBV DNA（拷贝/ml） TBil（μmol/L）
治疗前 治疗后 治疗前 治疗后 治疗前 治疗后
LA组 46 7.8 ± 2.5 6.2 ± 1.2 7.2 ± 1.7 4.1 ± 0.7 52.1 ± 23.1 27.3 ± 4.5
TA组 32 7.8 ± 1.9 6.1 ± 1.4 6.9 ± 1.1 4.2 ± 1.1 50.4 ± 16.9 28.3 ± 3.9
EN组 80 7.6 ± 1.9 6.8 ± 2.0 7.1 ± 1.2 4.5 ± 1.2 52.6 ± 15.0 32.7 ± 7.3
对照组 60 8.0 ± 1.2 9.1 ± 1.8 7.0 ± 0.9 5.8 ± 1.5 51.4 ± 20.3 44.5 ± 11.1
F值   1.047 11.275 0.367 12.198 1.442 15.645
P值   0.209 0.037 0.665 0.016 0.143 0.003
表4 不同核苷（酸）类似物治疗乙型肝炎肝硬化患者的病毒复制水平比较（μg/L，±s）
组别 例数 PC Ⅲ LN HA
治疗前 治疗后 治疗前 治疗后 治疗前 治疗后
LA组 46 275.6 ± 92.4 147.3 ± 65.1 180.1 ± 53.4 121.4 ± 38.5 398.4 ± 121.6 184.4 ± 92.7
TA组 32 281.4 ± 80.9 142.2 ± 67.9 177.3 ± 49.3 118.9 ± 29.9 380.3 ± 119.5 188.4 ± 98.2
EN组 80 286.5 ± 84.7 160.4 ± 55.2 179.3 ± 50.3 132.1 ± 40.2 386.7 ± 110.9 202.7 ± 84.5
对照组 60 279.5 ± 89.5 170.3 ± 49.9 181.5 ± 52.0 150.2 ± 41.2 394.5 ± 117.4 212.8 ± 77.4
F值   0.587 13.534 1.330 11.009 1.006 12.756
P值   0.488 0.015 0.321 0.022 0.378 0.019
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