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[用于乙型肝炎病毒感染相关慢加急性肝衰竭的核苷类似物:一项24个月生存分析]

[Nucleoside analogues for acute-on-chronic liver failure associated with hepatitis B virus infection: a 24-month survival analysis].

作者信息

Gao Haibin, Lin Minghua, Pan Chen, Lin Taijie, Wang Xiangmei, Zhou Rui, Li Xiaolou

机构信息

Department of severe Liver Diseases, Fuzhou Municipal Infectious Disease Hospital, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2015 Jan;23(1):17-22. doi: 10.3760/cma.j.issn.1007-3418.2015.01.006.

DOI:10.3760/cma.j.issn.1007-3418.2015.01.006
PMID:25751381
Abstract

OBJECTIVE

To investigate the effect of different nucleoside analogues on the long-term survival rate of patients with acute-on-chronic liver failure (ACLF) associated with hepatitis B virus (HBV) infection.

METHODS

One hundred and eighty patients with HBV-related ACLF were enrolled in this prospective cohort study and divided into a basic treatment group (n=30) and an antiviral treatment group, the latter of which was further subdivided into the lamivudine treatment group (n=66), telbivudine treatment group (n=38) and entecavir treatment group (n=46) according to voluntary choice by the patient.All study participants were followed-up for 24 months. The Kaplan-Meier method was applied for survival analysis.

RESULTS

The patients in the four antiviral treatment groups had statistically similar baseline clinical characteristics and 1-month survival rates (Breslow =4.475, P=0.215).However, the basic treatment group had a significantly lower survival rate than the antiviral treatment groups that received lamivudine, telbivudine, or entecavir (all P less than 0.05) at the treatment periods of 2, 3, 6, 12 and 18-months; however, these three treatment groups showed no significant differences in survival rates. At the time point of 24 months of treatment, the basic treatment group retained its lower rate of survival than the three antiviral treated groups (lamivudine:Breslow =5.604, P=0.018; telbivudine:Breslow =5.621, P=0.018; entecavir:Breslow =14.701, P less than 0.001); while the survival rates were similar for the lamivudine treatment group and the telbivudine treatment group at this time point, their survival rates were significantly lower than that of the entecavir treatment group (Breslow =4.010, P=0.045; Breslow =4.307, P=0.038).Stratification analysis showed that when the baseline was 30 less than PTA less than or equal to 40 or MELD less than or equal to 29 or HBV DNA more than or equal to 5 log10 IU/mL, the cumulative survival rates of the basic treatment group and antiviral treatment group were statistically similar even though the patients had completed 1 month of treatment After being treated for 2, 3, 6, 12, 18 and 24 months, the cumulative survival rates of the basic treatment group were consistently below those of the overall antiviral treatment group (P less than 0.05). The cumulative survival rate of the basic treatment group followed-up for 1 to 24 months, with PTA values between 20 and 30, was lower than that of the overall antiviral treatment group (P less than 0.05); two groups of patients with PTA less than or equal to 20 or MELD more than or equal to 30 were followed-up for 1 months to 24 months, and their cumulative survival rates showed no significant difference (P more than 0.05). Among the patients whose baseline was HBV DNA less than 5 log10 IU/mL, the comparison of survival rates between the basic treatment group and the overall antiviral treatment group showed no significant differences after treatment for 1, 2, 3, 6, 12 or 18 months, and the survival rate was lower than that of the overall antiviral treatment group (Breslow =4.055, P=0.044) after 24 months.

CONCLUSION

Nucleoside analogues can improve the long-term survival rate of HBV-related ACLF patients.Entecavir is preferred for the long-term treatment of these patients.Patients in the early and middle stages of this disease and HBV DNA-positive patients should adopt antiviral treatment as early as possible.

摘要

目的

探讨不同核苷类似物对乙型肝炎病毒(HBV)感染所致慢加急性肝衰竭(ACLF)患者长期生存率的影响。

方法

本前瞻性队列研究纳入180例HBV相关ACLF患者,分为基础治疗组(n = 30)和抗病毒治疗组,后者根据患者自愿选择进一步分为拉米夫定治疗组(n = 66)、替比夫定治疗组(n = 38)和恩替卡韦治疗组(n = 46)。所有研究参与者均随访24个月。采用Kaplan-Meier法进行生存分析。

结果

四个抗病毒治疗组患者的基线临床特征和1个月生存率在统计学上相似(Breslow = 4.475,P = 0.215)。然而,在治疗2、3、6、12和18个月时,基础治疗组的生存率显著低于接受拉米夫定、替比夫定或恩替卡韦治疗的抗病毒治疗组(均P < 0.05);然而,这三个治疗组的生存率无显著差异。在治疗24个月时,基础治疗组的生存率仍低于三个抗病毒治疗组(拉米夫定:Breslow = 5.604,P = 0.018;替比夫定:Breslow = 5.621,P = 0.018;恩替卡韦:Breslow = 14.701,P < 0.001);此时拉米夫定治疗组和替比夫定治疗组的生存率相似,但显著低于恩替卡韦治疗组(Breslow = 4.010,P = 0.045;Breslow = 4.307,P = 0.038)。分层分析显示,当基线为30 < PTA ≤ 40或MELD ≤ 29或HBV DNA ≥ 5 log10 IU/mL时,即使患者完成1个月治疗,基础治疗组和抗病毒治疗组的累积生存率在统计学上相似。在治疗2、3、6、12及18和24个月后时,基础治疗组的累积生存率始终低于整体抗病毒治疗组(P < 0.05)。基础治疗组随访1至24个月且PTA值在20至30之间的患者累积生存率低于整体抗病毒治疗组(P < 0.05);两组PTA ≤ 20或MELD ≥ 30的患者随访1至24个月,其累积生存率无显著差异(P > 0.05)。在基线HBV DNA < 5 log10 IU/mL的患者中,基础治疗组与整体抗病毒治疗组在治疗1、2、3、6、12或18个月后的生存率比较无显著差异,而在24个月时生存率低于整体抗病毒治疗组(Breslow = 4.055,P = 0.044)。

结论

核苷类似物可提高HBV相关ACLF患者的长期生存率。恩替卡韦是这些患者长期治疗的首选药物。本病早期和中期患者以及HBV DNA阳性患者应尽早采取抗病毒治疗。

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引用本文的文献

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The Comparative Efficacy and Safety of Entecavir and Lamivudine in Patients with HBV-Associated Acute-on-Chronic Liver Failure: A Systematic Review and Meta-Analysis.恩替卡韦与拉米夫定治疗HBV相关慢加急性肝衰竭患者的疗效与安全性比较:一项系统评价和Meta分析
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