Digestive and Liver Diseases Division, UT Southwestern Medical Center, Dallas, TX 75390-8887, USA.
J Viral Hepat. 2011 Jul;18(7):e167-74. doi: 10.1111/j.1365-2893.2010.01410.x. Epub 2010 Dec 8.
The reason(s) that hepatitis A virus (HAV) infection may progress infrequently to acute liver failure are poorly understood. We examined host and viral factors in 29 consecutive adult patients with HAV-associated acute liver failure enrolled at 10 sites participating in the US ALF Study Group. Eighteen of twenty-four acute liver failure sera were PCR positive while six had no detectable virus. HAV genotype was determined using phylogenetic analysis and the full-length genome sequences of the HAV from a cute liver failure sera were compared to those from self-limited acute HAV cases selected from the CDC database. We found that rates of nucleotide substitution did not vary significantly between the liver failure and non-liver failure cases and there was no significant variation in amino acid sequences between the two groups. Four of 18 HAV isolates were sub-genotype IB, acquired from the same study site over a 3.5-year period. Sub-genotype IB was found more frequently among acute liver failure cases compared to the non-liver failure cases (chi-square test, P < 0.01). At another centre, a mother and her son presented with HAV and liver failure within 1 month of each other. Predictors of spontaneous survival included detectable serum HAV RNA, while age, gender, HAV genotype and nucleotide substitutions were not associated with outcome. The more frequent appearance of rapid viral clearance and its association with poor outcomes in acute liver failure as well as the finding of familial cases imply a possible host genetic predisposition that contributes to a fulminant course. Recurrent cases of the rare sub-genotype IB over several years at a single centre imply a community reservoir of infection and possible increased pathogenicity of certain infrequent viral genotypes.
甲型肝炎病毒 (HAV) 感染很少进展为急性肝衰竭的原因尚不清楚。我们在参与美国急性肝衰竭研究组的 10 个地点连续招募的 29 例成人 HAV 相关性急性肝衰竭患者中，研究了宿主和病毒因素。24 例急性肝衰竭血清中有 18 例 PCR 阳性，6 例无病毒检测。采用系统发生分析确定 HAV 基因型，并将急性肝衰竭血清中的 HAV 全长基因组序列与从疾病预防控制中心数据库中选择的自限性急性 HAV 病例进行比较。我们发现，衰竭病例和非衰竭病例之间核苷酸替换率没有显著差异，两组之间氨基酸序列也没有显著差异。18 例 HAV 分离株中有 4 例为亚基因型 IB，来自同一研究地点，在 3.5 年内获得。与非肝衰竭病例相比，亚基因型 IB 在急性肝衰竭病例中更为常见（卡方检验，P < 0.01）。在另一个中心，一位母亲和她的儿子在彼此相隔 1 个月的时间内出现了 HAV 和肝衰竭。自发生存的预测因素包括可检测到的血清 HAV RNA，而年龄、性别、HAV 基因型和核苷酸替换与结局无关。在急性肝衰竭中，快速病毒清除的更频繁出现及其与不良结局的关联，以及家族性病例的发现，暗示可能存在宿主遗传易感性，导致暴发性病程。在单个中心的几年内，罕见的亚基因型 IB 的复发性病例表明存在社区感染的储库，以及某些罕见病毒基因型可能具有更高的致病性。
