Department of Hepatology, Toranomon Hospital, Tokyo 105-0001, Japan.
Intervirology. 2013;56(1):13-21. doi: 10.1159/000339993. Epub 2012 Aug 16.
Substitution of amino acid 70 and/or 91 in the core region of hepatitis C virus (HCV) genotype 1b (HCV-1b) is an important predictor of hepatocellular carcinoma (HCC), but its impact on HCC in nonresponders to interferon (IFN) and ribavirin (RIB) combination therapy is not clear.
A total of 292 patients with HCV-1b-related chronic liver disease who did not achieve a sustained virological response to 24-48 weeks of IFN+RIB combination therapy were included in a follow-up study to investigate the risk factors for HCC.
Sixteen patients developed HCC during the follow-up. The cumulative HCC rates were 5.0, 13.1 and 16.9% at the end of 3, 5 and 7 years, respectively. Multivariate analysis identified substitution of core amino acid 70 (Gln70/His70; hazard ratio 4.64, p = 0.018) and low serum levels of high-density lipoprotein cholesterol (<50 mg/dl; hazard ratio 9.35, p = 0.041) as determinants of HCC. Gender, stage of fibrosis and interleukin-28B showed no such relationship.
Amino acid substitution in the core region of HCV-1b and low serum levels of high-density lipoprotein cholesterol are significant and independent predictors of HCC in nonresponders to IFN+RIB combination therapy. These results emphasize the importance of viral and lipid metabolic factors in the development of HCC after combination therapy.
丙型肝炎病毒（HCV）基因型 1b（HCV-1b）核心区氨基酸 70 和/或 91 的取代是肝细胞癌（HCC）的一个重要预测因子，但它对干扰素（IFN）和利巴韦林（RIB）联合治疗无应答者 HCC 的影响尚不清楚。
共纳入 292 例 HCV-1b 相关慢性肝病患者，这些患者对 24-48 周 IFN+RIB 联合治疗未能获得持续病毒学应答，对其进行了随访研究，以探讨 HCC 的危险因素。
16 例患者在随访期间发生 HCC。3、5 和 7 年末的累积 HCC 发生率分别为 5.0%、13.1%和 16.9%。多因素分析确定核心氨基酸 70（Gln70/His70；危险比 4.64，p=0.018）和血清高密度脂蛋白胆固醇水平低（<50mg/dl；危险比 9.35，p=0.041）是 HCC 的决定因素。性别、纤维化分期和白细胞介素-28B 则与 HCC 无相关性。
HCV-1b 核心区氨基酸取代和血清高密度脂蛋白胆固醇水平低是 IFN+RIB 联合治疗无应答者 HCC 的显著且独立的预测因子。这些结果强调了病毒和脂质代谢因素在联合治疗后 HCC 发生中的重要性。
