Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
German Center for Infection Research (DZIF), Partner Side Hannover Medical School, Hannover, Germany.
Hepatology. 2017 Feb;65(2):414-425. doi: 10.1002/hep.28876. Epub 2016 Nov 30.
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.
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).
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。
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。
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。