基线HBV DNA水平对代偿期乙型肝炎肝硬化患者抗病毒治疗后临床转归的影响

Influence of baseline HBV DNA level on the clinical outcome of patients with compensated hepatitis B cirrhosis after antiviral therapy

目的分析基线HBV DNA水平对代偿期乙型肝炎肝硬化患者抗病毒治疗后临床转归的影响。方法选取首都医科大学附属北京友谊医院肝病中心2005年-2015年代偿期乙型肝炎肝硬化患者106例,给予核苷和核苷酸类药物抗病毒治疗,对患者进行前瞻性随访观察3年。按治疗前HBV DNA水平将患者分为3组,即HBV DNA<105IU/ml组、105~107IU/ml组和>107IU/ml组。比较3组患者基线特征、抗病毒治疗疗效及肝脏相关终点事件(LREs)发生率。组间比较采用重复测量资料的方差分析或Friedman Test检验;计数资料组间比较采用χ~2检验。采用Kaplan-Meier法计算LREs发生率并绘制生存曲线,各组之间的比较采用log-rank对数秩检验。结果 3组患者在年龄、性别、HBeAg、生化指标、肝脏硬度及CTP评分上差异均无统计学意义(P值均>0.05)。HBV DNA水平随时间的变化趋势差异有统计学意义(F=8.35,P<0.05);3组间比较HBV DNA水平的变化差异也有统计学意义(F=13.95,P<0.05)。3组患者在治疗6个月时HBV DNA水平较基线都显著下降,其中HBV DNA<105IU/ml组和105~107IU/ml组患者实现中位HBV DNA低于检测限,而HBV DNA>107IU/ml组在治疗12个月后实现中位HBV DNA低于检测限。在治疗12个月及24个月时,3组HBV DNA阴转率差异无统计学意义(χ~2值分别为5.97、6.84,P值均>0.05),在治疗36个月时,3组HBV DNA阴转率分别为95.7%、88.0%和77.8%,差异有统计学意义(χ~2=12.75,P<0.05)。3组LREs发生率差异无统计学意义(P>0.05)。结论乙型肝炎肝硬化患者抗病毒治疗后HBV DNA水平显著下降,高水平复制的患者病毒学应答速度较慢,但基线HBV DNA水平对抗病毒治疗后3年内LREs的发生率无显著影响。

Objective To investigate the influence of baseline HBV DNA level on the clinical outcome of patients with compensated hepatitis B cirrhosis after antiviral therapy. Methods A total of 106 patients with compensated hepatitis B cirrhosis who were treated in Liver Research Center,Beijing Friendship Hospital,Capital Medical University from 2005 to 2015 were enrolled and were given antiviral therapy with nucleos（ t） ide analogues. A three-year prospective follow-up was performed for all patients. According to the baseline HBV DNA level,the patients were divided into HBV DNA 105 IU/ml group,105-107 IU/ml group,and 107 IU/ml group. The three groups were compared in terms of baseline characteristics,outcome of antiviral therapy,and incidence rate of liver-related events（ LREs）. A repeated-measures analysis of variance or the Friedman rank sum test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to calculate the incidence rates of LREs and plot survival curves,and the log-rank test was used for comparison between groups. Results There were no significant differences between the three groups in age,sex,HBeAg,biochemical parameters,liver stiffness,and Child-Turcotte-Pugh score（ all P 〉0. 05）. There were significant differences between the three groups in the change trend of HBV DNA level（ F = 8. 35,P〈 0. 05） and the degree of such change（ F = 13. 95,P 〈0. 05）. At 6 months of treatment,all three groups had a significant reduction in HBV DNA level,and the HBV DNA 〈105 IU/ml group and the 105-107 IU/ml group achieved a median HBV DNA level of below the limit of detection,while the HBV DNA 〉107 IU/ml group achieved such a level at 12 months of treatment. At 12 and 24 months of treatment,there was no significant difference in HBV DNA clearance rate between the three groups（ χ~2= 5. 97 and 6. 84,both P 〉0. 05）; at 36 months of treatment,there was a significant difference in HBV DNA clearance rate between the three groups（ 95. 7% vs 88. 0% vs 77. 8%,χ~2= 12. 75,P〈0. 05）. There was no significant difference in the incidence rate of LREs between the three groups（ P 〉0. 05）. Conclusion Patients with compensated hepatitis B cirrhosis have a significant reduction in HBV DNA level after antiviral therapy. Although patients with a high level of replication have slow virologic response,baseline HBV DNA level has no influence on the incidence rate of LREs within 3 years of antiviral therapy.