Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
Department of Gastroenterology and Hepatology, University Hospital of Essen, Essen, Germany.
Hepatology. 2019 Mar;69(3):993-1003. doi: 10.1002/hep.30279. Epub 2019 Feb 11.
Acute hepatitis B virus (HBV) infection remains a frequent cause of acute liver failure (ALF) worldwide. ALF occurs in 0.1%-0.5% of infected patients. The aim of this study was to scrutinize the outcome of patients with HBV-induced ALF and mutational patterns of HBV variants, which might contribute to ALF. From 2005 to 2016, 42 patients were treated for HBV-induced ALF in the University Hospital Essen, Germany. Clinical and virological data from these patients were collected. As a control, 38 patients with acute hepatitis B (AHB) without liver failure were included. The HBV genome was sequenced by next-generation sequencing (NGS). Mutations that were found by NGS were analyzed in vitro. Of 42 patients, 8 had ALF without spontaneous recovery (NSR): Seven patients underwent liver transplantation (LT) and one patient died before LT. Of 42 patients, 34 (81%) had spontaneous recovery (SR) and cleared the infection, achieving either anti-HBs seroconversion or hepatitis B surface antigen (HBsAg) loss. HBV genotype (GT)-D was the most frequent GT in patients with ALF. Mutations in HBV core, preS2, and small hepatitis B surface antigen (SHB) were more frequent in patients with ALF-NSR compared with those with ALF-SR or AHB. Amino acid deletions (del; 16-22 and 20-22) in preS2 and SHB mutation L49R were exclusively detected in patients with ALF-NSR. In vitro analyses reveal that these mutations did not influence HBsAg secretion or infectivity. Conclusion: HBV GT-D and increased variability in HBV core, preS2 region, and SHB are associated with a worse clinical outcome of acute HBV infection.
急性乙型肝炎病毒 (HBV) 感染仍然是全球急性肝衰竭 (ALF) 的常见原因。ALF 发生在 0.1%-0.5%的感染患者中。本研究旨在探讨 HBV 诱导的 ALF 患者的结局和可能导致 ALF 的 HBV 变异的突变模式。2005 年至 2016 年，德国埃森大学医院治疗了 42 例 HBV 诱导的 ALF 患者。收集了这些患者的临床和病毒学数据。作为对照，纳入了 38 例无肝衰竭的急性乙型肝炎 (AHB) 患者。通过下一代测序 (NGS) 对 HBV 基因组进行测序。通过 NGS 发现的突变在体外进行了分析。在 42 例患者中，8 例无自发恢复 (NSR) 的 ALF：7 例患者接受了肝移植 (LT)，1 例患者在 LT 前死亡。在 42 例患者中，34 例 (81%) 有自发恢复 (SR) 并清除了感染，实现了抗-HBs 血清转换或乙型肝炎表面抗原 (HBsAg) 丢失。ALF 患者中最常见的 HBV 基因型 (GT) 是 GT-D。与 ALF-SR 或 AHB 患者相比，ALF-NSR 患者的 HBV 核心、前 S2 和小乙型肝炎表面抗原 (SHB) 中突变更为频繁。前 S2 和 SHB 突变 L49R 中的氨基酸缺失 (del; 16-22 和 20-22) 仅在 ALF-NSR 患者中检测到。体外分析表明，这些突变不会影响 HBsAg 分泌或感染性。结论：HBV GT-D 和 HBV 核心、前 S2 区和 SHB 中的变异性增加与急性 HBV 感染的临床结局较差相关。
