Seiz Pia L, Slanina Heiko, Ziebuhr John, Gerlich Wolfram H, Glebe Dieter, Schüttler Christian G
Institute of Medical Virology, Justus Liebig University Giessen, National Reference Center for Hepatitis B and D Viruses, German Center for Infection Research, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany.
Institute of Medical Virology, Justus Liebig University Giessen, National Reference Center for Hepatitis B and D Viruses, German Center for Infection Research, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany.
Int J Med Microbiol. 2015 Oct;305(7):663-72. doi: 10.1016/j.ijmm.2015.08.016. Epub 2015 Aug 21.
Hepatitis B virus (HBV) causes acute or chronic hepatitis B. Local outbreaks of HBV infections in skilled nursing facilities is a matter of growing concern in developed countries. Here, we investigated two outbreaks of hepatitis B that recently occurred in nursing homes in Germany. The outbreak at location A was associated with acute fulminant hepatitis with fatal outcome in several cases, while individuals infected at location B developed asymptomatic or mild hepatitis B. Sequence analysis of viruses involved in these outbreaks revealed different, but unique HBV strains for each location. Each of the strains produced high viremia of more than 10(9) virions/mL serum. We found that the mild course of hepatitis B at location B was caused by a circulating wild-type HBV genotype A2 strain, which is commonly found in Central Europe. Complete genome sequences of isolates obtained from infected patients revealed nearly 100% sequence identity at the nucleotide level as well as expression of HBV e protein (HBeAg), a known T cell tolerogen in the incubation or chronic phases of HBV infection. By contrast, the outbreak at location A was associated with an HBV genotype D2 variant that lacked HBeAg expression, suggesting that immunopathology and selection of specific HBV variants played a major role in the severe (or even fulminant) acute hepatitis observed at location A. Importantly, all patients were diagnosed with type 2 diabetes mellitus, a known risk factor for healthcare-associated transmission of HBV. The study leads us to suggest that, besides strict adherence to hygiene standards, additional efforts are required to reduce the risk of HBV transmission and fulminant disease progression in healthcare settings and nursing homes. In this context, a general screening for HBsAg and active hepatitis B vaccination should be considered for people living in nursing homes, especially for those with diagnosed diabetes or other predisposing factors for HBV transmission.
乙型肝炎病毒（HBV）可引发急性或慢性乙型肝炎。在发达国家，专业护理机构中局部爆发的HBV感染问题日益受到关注。在此，我们调查了德国养老院近期发生的两起乙型肝炎疫情。地点A的疫情与急性暴发性肝炎相关，数例患者出现致命后果，而在地点B感染的个体则发展为无症状或轻度乙型肝炎。对这些疫情中涉及的病毒进行序列分析发现，每个地点的病毒株不同但具有独特性。每个毒株均产生了超过10⁹病毒颗粒/毫升血清的高病毒血症。我们发现，地点B的乙型肝炎病程较轻是由一种在中欧常见的循环野生型HBV基因型A2毒株引起的。从感染患者分离出的病毒株的完整基因组序列在核苷酸水平上显示出近100%的序列同一性，并且表达了HBV e抗原（HBeAg），这是一种在HBV感染的潜伏期或慢性期已知的T细胞耐受原。相比之下，地点A的疫情与一种缺乏HBeAg表达的HBV基因型D2变体相关，这表明免疫病理学和特定HBV变体的选择在地点A观察到的严重（甚至暴发性）急性肝炎中起了主要作用。重要的是，所有患者均被诊断为2型糖尿病，这是已知的与医疗保健相关的HBV传播风险因素。该研究促使我们提出，除了严格遵守卫生标准外，还需要做出额外努力，以降低医疗保健机构和养老院中HBV传播及暴发性疾病进展的风险。在此背景下，应考虑对养老院中的居民进行HBsAg普遍筛查和积极的乙型肝炎疫苗接种，特别是对于那些已诊断患有糖尿病或其他HBV传播易感因素的人群。
