Hepatitis delta-associated mortality in HIV/HBV-coinfected patients
Hepatitis delta-associated mortality in HIV/HBV-coinfected patients
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DOI：
10.1016/j.jhep.2016.10.007
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发表时间：
2017-02-01
影响因子：
25.7
通讯作者：
Wandeler, Gilles
中科院分区：
文献类型：
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作者：
Beguelin, Charles;Moradpour, Darius;Wandeler, Gilles
背景与目的：丁型肝炎病毒（HDV）感染可加速B型肝炎病毒（HBV）相关性肝病的进展。我们评估了HDV感染的流行病学特征，在全国范围内的瑞士艾滋病毒队列研究，并评估其对临床outcomes.Methods的影响：所有的HIV感染的患者与阳性B表面抗原检测被认为是抗HDV抗体和测试。在抗HDV阳性患者中进行HDV扩增和测序。采用描述性统计方法比较了HDV阳性和HDV阴性个体在开始抗逆转录病毒治疗时的人口统计学和临床特征，以及死亡原因。采用Kaplan-Meier和考克斯多因素回归分析HDV感染与总死亡率、肝脏相关死亡率以及肝细胞癌（HCC）发生率的关系。HDV感染率为15.4%（119/771，95%CI：12.9-18.0），HDV阳性者中有HDV复制者占62.9%（73/116）。与未感染HDV的患者相比，感染HDV的患者更可能是注射毒品的人（60.6%对9.1%）和具有阳性丙型肝炎病毒（HCV）血清学（73.1%对17.8%）。HDV感染与总死亡率（调整后的风险比2.33，95%CI 1.41-3.84）、肝脏相关死亡率（7.71，3.13-18.97）和HCC发生率（9.30，3.03-28.61）密切相关。当注射毒品的人或HCV合并感染的患者被排除在分析之外时，结果相似。结论：在瑞士HIV队列研究（SHCS）中，B型肝炎表面抗原阳性患者中HDV的患病率很高，HDV感染与死亡率和肝脏相关事件（包括HCC）独立相关。丁型肝炎病毒（HDV）感染加速了B型肝炎病毒（HBV）相关肝病的进展。在瑞士全国范围内的HIV感染者队列中，15%的HBV合并感染患者具有HDV感染的抗体，其中大多数具有活跃的HDV复制。与未感染HDV的人相比，HDV感染者死亡的可能性高2.5倍，死于肝脏相关原因的可能性高8倍，患肝癌的可能性高9倍。我们的研究结果强调了预防计划（包括HBV疫苗接种），系统筛查高危人群以及密切监测的必要性，并强调了开发慢性HDV感染新疗法的重要性。(C)2016年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background & Aims: Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. We assessed the epidemiological characteristics of HDV infection in the nationwide Swiss HIV Cohort Study and evaluated its impact on clinical outcomes.Methods: All HIV-infected patients with a positive hepatitis B surface antigen test were considered and tested for anti-HDV antibodies. HDV amplification and sequencing were performed in anti-HDV-positive patients. Demographic and clinical characteristics at initiation of antiretroviral therapy, as well as causes of death were compared between HDV-positive and HDV-negative individuals using descriptive statistics. Kaplan-Meier and multivariable Cox regression analyses were used to evaluate the association between HDV infection and overall mortality, liver-related mortality as well as incidence of hepatocellular carcinoma (HCC).Results: Of 818 patients with a positive hepatitis B surface antigen tests, 771 (94%) had a stored serum sample available and were included. The prevalence of HDV infection was 15.4% (119/771, 95% CI: 12.9-18.0) and the proportion of HDV-positive patients with HDV replication 62.9% (73/116). HDV-infected patients were more likely to be persons who inject drugs (60.6% vs. 9.1%) and to have a positive hepatitis C virus (HCV) serology (73.1% vs. 17.8%) compared to HDV-uninfected ones. HDV infection was strongly associated with overall death (adjusted hazard ratio 2.33, 95% CI 1.41-3.84), liver-related death (7.71, 3.13-18.97) and with the occurrence of HCC (9.30, 3.03-28.61). Results were similar when persons who inject drugs or HCV-coinfected patients were excluded from the analyses.Conclusions: The prevalence of HDV in hepatitis B surface antigen-positive patients in the Swiss HIV Cohort Study (SHCS) is high and HDV infection is independently associated with mortality and liver-related events, including HCC.Lay summary: Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. In a nationwide cohort of HIV-infected individuals in Switzerland, 15% of HBV-coinfected patients had antibodies to HDV infection, of which a majority had active HDV replication. HDV-infected individuals were 2.5 times more likely to die, eight times more likely to die from a liver-related cause and nine times more likely to develop liver cancer compared to HDV-uninfected ones. Our results emphasize the need for prevention programs (including HBV vaccination), the systematic screening of at risk populations as well as close monitoring, and underline the importance of developing new treatments for chronic HDV infection. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.