Substitution of amino acid 70 in the hepatitis C virus core region of genotype 1b is an important predictor of elevated alpha-fetoprotein in patients without hepatocellular carcinoma
Substitution of amino acid 70 in the hepatitis C virus core region of genotype 1b is an important predictor of elevated alpha-fetoprotein in patients without hepatocellular carcinoma
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DOI：
10.1002/jmv.21202
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发表时间：
2008-08-01
影响因子：
12.7
通讯作者：
Kumada, Hiromitsu
中科院分区：
文献类型：
--
作者：
Akuta, Norio;Suzuki, Fumitaka;Kumada, Hiromitsu
先前的研究发现基因型1b丙型肝炎病毒核心区域（HCV-1b核心区域）的氨基酸（aa）替换和血清甲胎蛋白（AFP）水平升高是聚乙二醇化干扰素（PEG-IFN）加利巴韦林（RBV）病毒学反应差的预测因素，也是肝癌发生的危险因素。本研究在569例日本HCV-1b患者中，评估了作为肝癌发生替代标志物的HCV-1b核心区aa替代对AFP水平的影响，并探讨了AFP升高的预测因素（>= 11 μ g/L）。27.4%的患者检测到高AFP水平。在109例接受干扰素单药治疗并随访15年的患者中，AFP异常患者的肝癌发生率明显高于正常患者。569例患者的多因素分析发现，纤维化分期（f3,4）、天冬氨酸转氨酶（>= 76 IU/L）、aa 70替代（谷氨酰胺或组氨酸）和血小板计数（< 15.0 × 10(4)/ μ L）是AFP升高的重要决定因素。在49例AFP水平异常和aa - 70替代的患者中，接受PEG-IFN+RBV治疗的患者中，非病毒学应答者的AFP正常化率（28.6%）明显低于短暂（71.4%）和持续（100%）病毒学应答者。结果表明，HCV-1b核心区a70的替换是非hcc患者AFP升高的重要预测因子，根除突变病毒可使AFP恢复正常。这些结果强调了根除a70突变型病毒对降低肝癌发生风险的重要性。
Previous studies identified amino acid (aa) substitutions of the, hepatitis C virus core region of genotype 1b (HCV-1b core region) and elevated serum alpha-fetoprotein (AFP) levels as predictors of poor virologic response to pegylated interferon (PEG-IFN) plus ribavirin (RBV), and also as risk factors for hepatocarcinogenesis. The present study evaluated the impact of aa substitutions of HCV-1b core region on AFP, as a surrogate marker of hepatocarcinogenesis, on AFP levels in 569 Japanese patients with HCV-1b but without HCC, and investigated the predictive factors of elevated AFP (>= 11 mu g/L). High AFP levels were detected in 27.4% of the patients. The rate of hepatocarcinogenesis in a group of 109 patients who received IFN monotherapy and followed-up for 15 years, was significantly higher in patients with abnormal than normal AFP. Multivariate analysis of 569 patients identified fibrosis stage (F3,4), aspartate aminotransferase (>= 76 IU/L), substitution of aa 70 (glutamine or histidine), and platelet count (< 15.0 x 10(4)/mu l) as significant determinants of elevated AFP. In 49 patients with abnormal AFP levels and substitutions at aa 70 who were treated with PEG-IFN+RBV, the rate of normalization of AFP was significantly lower in non-virological responders (28.6%) than in transient (71.4%) and sustained (100%) virological responders. The results indicated that substitution of aa 70 of HCV-1b core region is an important predictor of elevated AFP in non-HCC patients, and that eradication of the mutant virus normalizes AFP. The results highlight the importance of eradication of mutant type virus of aa 70 for reducing the risk of hepatocarcinogenesis.