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乙型肝炎 delta 病毒感染的抗病毒治疗与肝脏相关并发症

Antiviral treatment and liver-related complications in hepatitis delta.

机构信息

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.

German Center for Infection Research (DZIF), Partner Side Hannover Medical School, Hannover, Germany.

出版信息

Hepatology. 2017 Feb;65(2):414-425. doi: 10.1002/hep.28876. Epub 2016 Nov 30.

Abstract

UNLABELLED

Hepatitis delta virus (HDV) is the most severe form of viral hepatitis. Pegylated interferon alfa (PEG-IFNα) is effective in only 25%-30% of patients and is associated with frequent side effects. The aim of this study was to analyze the clinical long-term outcome of hepatitis delta in relation to different antiviral treatment strategies. We studied 136 anti-HDV-positive patients who were followed for at least 6 months in a retrospective single-center cohort (mean time of follow-up, 5.2 years; range, 0.6-18.8). Liver cirrhosis was already present in 62 patients at first presentation. Twenty-nine percent of patients did not receive any antiviral treatment, 38% were treated with interferon alfa (IFNα)-based therapies, and 33% received nucleos(t)ide analogues (NAs) only. Clinical endpoints defined as hepatic decompensation (ascites, encephalopathy, and variceal bleeding), hepatocellular carcinoma, liver transplantation, and liver-related death developed in 55 patients (40%). Patients who received IFNα-based therapies developed clinical endpoints less frequently than those treated with NA (P = 0.02; HR, 4.0) or untreated patients (P = 0.05; HR, 2.2; 17%, 64%, and 44%), respectively, which was significant in both chi-square and Kaplan-Meier analysis. In addition, considering various clinical and virological parameters, IFNα therapy was independently associated with a more benign clinical long-term outcome in multivariate logistic regression analysis (P = 0.04; odds ratio, 0.25; 95% confidence interval, 0.07-0.9). Loss of HDV RNA during follow-up was more frequent in IFNα-treated patients and strongly linked with a lower likelihood to experience liver-related complications.

CONCLUSION

IFNα-based antiviral therapy of hepatitis delta was independently associated with a lower likelihood for clinical disease progression. Durable undetectability of HDV RNA is a valid surrogate endpoint in the treatment of hepatitis delta. (Hepatology 2017;65:414-425).

摘要

目的

分析不同抗病毒治疗策略与乙型肝炎 delta 病毒(HDV)感染临床长期结局的关系。

方法

我们对在回顾性单中心队列中接受至少 6 个月随访的 136 例抗-HDV 阳性患者进行了研究(平均随访时间为 5.2 年,范围为 0.6-18.8 年)。初次就诊时已有 62 例患者存在肝硬化。29%的患者未接受任何抗病毒治疗,38%的患者接受干扰素α(IFNα)为基础的治疗,33%的患者仅接受核苷(酸)类似物(NAs)治疗。55 例患者(40%)出现了肝性失代偿(腹水、肝性脑病和静脉曲张出血)、肝细胞癌、肝移植和与肝脏相关的死亡等临床终点。与接受 NAs 治疗的患者相比,接受 IFNα 为基础治疗的患者发生临床终点的频率较低(P=0.02;HR=4.0),与未治疗的患者相比,差异亦有统计学意义(P=0.05;HR=2.2;17%、64%和 44%),卡方检验和 Kaplan-Meier 分析均显示该差异有统计学意义。此外,在考虑了各种临床和病毒学参数后,多变量逻辑回归分析显示 IFNα 治疗与临床长期结局的改善独立相关(P=0.04;比值比,0.25;95%可信区间,0.07-0.9)。在随访期间,HDV RNA 丢失在 IFNα 治疗患者中更为常见,与发生肝相关并发症的可能性降低密切相关。

结论

HDV 感染的 IFNα 为基础的抗病毒治疗与临床疾病进展的可能性降低独立相关。HDV RNA 持续不可检测是乙型肝炎 delta 病毒治疗的有效替代终点。

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