Tanaka Yasuhito, Mukaide Motokazu, Orito Etsuro, Yuen Man-Fung, Ito Kiyoaki, Kurbanov Fuat, Sugauchi Fuminaka, Asahina Yasuhiro, Izumi Namiki, Kato Michio, Lai Ching-Lung, Ueda Ryuzo, Mizokami Masashi
Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
J Hepatol. 2006 Nov;45(5):646-53. doi: 10.1016/j.jhep.2006.06.018. Epub 2006 Aug 10.
BACKGROUND/AIMS: Hepatitis B virus genotype C (HBV/C) has been classified into two geographically distinct subgenotypes; HBV/C1/Cs (Southeast Asia) and HBV/C2/Ce (East Asia).
Viral differences in enhancer II/core promoter and precore regions between the subgenotypes and their association with hepatocellular carcinoma (HCC) were assessed in a matched cross-sectional control study of 118 carriers (from Hong Kong) with HBV/C1/Cs (48.0 years, 81% male, 40% HBeAg+, 44% HCC) and 210 HBV/C2/Ce (172 from Japan, 38 from Hong Kong) (50.2 years, 78% male, 30% HBeAg+, 46% HCC).
Univariate analyses showed that mutation V1753 was predictive for HCC among HBeAg-positive-C1/Cs-carriers (P=0.0055), and T1653 among HBeAg-positive-C2/Ce-carriers (P=0.018), and T1653 or V1753 or T1762/A1764 among HBeAg-negative-C2/Ce-carriers (P<0.05). In the multivariate analysis on all HBV/C subjects, independent predictive factors for HCC were subgenotype C2/Ce (odds ratio, 4.21; 95% confidence interval, 1.07-16.23), T1653 (3.64; 1.93-6.86), V1753 (3.07; 1.66-5.65) and T1762/A1764 (2.58; 1.21-5.49) mutations, age (50 years), gender (male) and HBeAg (positive).
Our data indicate that T1653 and/or V1753 mutations in addition to T1762/A1764 are differently associated with HCC in context of HBeAg status among HBV/C1/Cs and C2/Ce-carriers. HBV/C subgenotypes have specific mutation patterns, which is probably responsible for increased carcinogenesis of HBV/C2/Ce.
背景/目的：乙型肝炎病毒C基因型（HBV/C）已被分为两种在地理上不同的亚基因型；HBV/C1/Cs（东南亚）和HBV/C2/Ce（东亚）。
在一项匹配的横断面对照研究中，评估了118例HBV/C1/Cs携带者（来自香港）（48.0岁，81%为男性，40%HBeAg阳性，44%有肝细胞癌）和210例HBV/C2/Ce携带者（172例来自日本，38例来自香港）（50.2岁，78%为男性，30%HBeAg阳性，46%有肝细胞癌）亚基因型之间增强子II/核心启动子和前核心区的病毒差异及其与肝细胞癌（HCC）的关联。
单因素分析显示，V1753突变在HBeAg阳性的C1/Cs携带者中对肝细胞癌具有预测性（P=0.0055），T1653在HBeAg阳性的C2/Ce携带者中具有预测性（P=0.018），T1653或V1753或T1762/A1764在HBeAg阴性的C2/Ce携带者中具有预测性（P<0.05）。在对所有HBV/C受试者的多因素分析中，肝细胞癌的独立预测因素为亚基因型C2/Ce（比值比，4.21；95%置信区间，1.07 - 16.23）、T1653（3.64；1.93 - 6.86）、V1753（3.07；1.66 - 5.65）和T1762/A1764（2.58；1.21 - 5.49）突变、年龄（50岁）、性别（男性）和HBeAg（阳性）。
我们的数据表明，除了T1762/A1764之外，T1653和/或V1753突变在HBV/C1/Cs和C2/Ce携带者的HBeAg状态背景下与肝细胞癌的关联不同。HBV/C亚基因型具有特定的突变模式，这可能是HBV/C2/Ce致癌性增加的原因。
