Heringlake S, Osterkamp S, Trautwein C, Tillmann H L, Böker K, Muerhoff S, Mushahwar I K, Hunsmann G, Manns M P
Department of Gastroenterology and Hepatology, Medical University Hannover, Germany.
Lancet. 1996 Dec 14;348(9042):1626-9. doi: 10.1016/S0140-6736(96)04413-3.
The GB virus C (GBV-C) and the hepatitis G virus (HGV) have been detected in patients with acute indeterminant hepatitis and post-transfusion hepatitis. However, the role of the new hepatitis viruses in the aetiology of fulminant hepatitis is little understood. We investigated the presence of GBV-C/HGV in patients with fulminant hepatic failure.
Serum samples from 22 German patients with fulminant hepatic failure and 106 symptom-free blood donors (controls) were studied for presence of GBV-C RNA by seminested reverse transcriptase PCR. Primer sequences were derived from the published gene sequences of the conserved NS3 region of the GBV-C prototype and the published isolates. Nucleotide and amino acid sequences of GBV-C-positive isolates, the control RNA, and the published HGV and GBV-C prototype sequences were compared by multiple sequence alignment. We also compared the GBV-C sequences of virus-positive patients who had fulminant hepatic failure with those of 19 patients with chronic hepatitis from our centre. In addition, we searched databases and published papers for further GBV-C helicase sequences in patients with non-fulminant hepatitis.
GBV-C RNA was detected in 11 (50%) of the 22 patients with fulminant hepatic failure and in five (4.7%) of 106 control-group blood donors. Among the patients with fulminant hepatic failure, six of seven with fulminant hepatitis B and five of ten with fulminant non-A-E hepatitis were positive for GBV-C RNA. Analysis of nucleic acid sequences showed six mutations at defined positions in all 11 patients with fulminant hepatic failure who were positive for GBV-C. None of these mutations were found in the five GBV-C-positive control-group blood donors. Of the six nucleotide changes, four caused no amino acid changes, whereas two mutations at position 100 (G to T) and 102 (T to C) led to an alanine to serine change in the predicted translation product. However, comparison with GBV-C sequences of patients with non-fulminant hepatitis showed that this amino acid mutation was not specific for fulminant hepatic failure. The sequence-motif containing the six nucleotide mutations detected in all patients with fulminant hepatic failure was found in only two of 19 German patients with chronic hepatitis from our centre, and in only one of 88 GBV-C sequences from non-fulminant patients reported by others.
The frequency of GBV-C RNA is higher in fulminant hepatic failure than in any other group of patients with hepatitis, particularly in patients with fulminant hepatitis B or fulminant non-A-E hepatitis. A specific strain of GBV-C may occur in serum of German patients with fulminant hepatic failure.
在急性不明原因肝炎患者和输血后肝炎患者中已检测到GB病毒C（GBV-C）和庚型肝炎病毒（HGV）。然而，人们对这些新型肝炎病毒在暴发性肝炎病因学中的作用了解甚少。我们调查了暴发性肝衰竭患者中GBV-C/HGV的存在情况。
采用半巢式逆转录聚合酶链反应（seminested reverse transcriptase PCR）研究了22例德国暴发性肝衰竭患者和106例无症状献血者（对照组）的血清样本中GBV-C RNA的存在情况。引物序列来源于已发表的GBV-C原型保守NS3区域的基因序列和已发表的分离株。通过多序列比对比较GBV-C阳性分离株、对照RNA以及已发表的HGV和GBV-C原型序列的核苷酸和氨基酸序列。我们还比较了暴发性肝衰竭病毒阳性患者与本中心19例慢性肝炎患者的GBV-C序列。此外，我们在数据库和已发表的论文中搜索非暴发性肝炎患者中更多的GBV-C解旋酶序列。
22例暴发性肝衰竭患者中有11例（50%）检测到GBV-C RNA，106例对照组献血者中有5例（4.7%）检测到。在暴发性肝衰竭患者中，7例暴发性乙型肝炎患者中有6例，10例暴发性非甲-戊型肝炎患者中有5例GBV-C RNA呈阳性。核酸序列分析显示，在所有11例GBV-C阳性的暴发性肝衰竭患者中，特定位置有6个突变。在5例GBV-C阳性的对照组献血者中未发现这些突变。在6个核苷酸变化中，4个未引起氨基酸变化，而在第100位（G到T）和第102位（T到C）的两个突变导致预测翻译产物中的丙氨酸变为丝氨酸。然而，与非暴发性肝炎患者的GBV-C序列比较显示，这种氨基酸突变并非暴发性肝衰竭所特有。在本中心19例德国慢性肝炎患者中，只有2例以及在其他人报道的88例非暴发性患者的GBV-C序列中，只有1例发现了所有暴发性肝衰竭患者中检测到的含有6个核苷酸突变的序列基序。
暴发性肝衰竭患者中GBV-C RNA的频率高于任何其他肝炎患者组，尤其是暴发性乙型肝炎或暴发性非甲-戊型肝炎患者。德国暴发性肝衰竭患者血清中可能出现一种特定的GBV-C毒株。
