Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, Chiba City, Chiba 260-8670, Japan.
J Hepatol. 2010 Jan;52(1):72-8. doi: 10.1016/j.jhep.2009.10.001. Epub 2009 Oct 23.
BACKGROUND & AIMS: To determine whether amino acid mutations in the core region of hepatitis C virus (HCV) genotype 1 are associated with response to interferon (IFN) therapy and development of hepatocellular carcinoma (HCC).
We followed up 361 patients (median duration, 121 months), and IFN monotherapy was administered to 275 (76%) [sustained virological response (SVR) rate, 26.5%]. Using pretreatment sera, mutations at core residues 70 and 91 were analyzed [double wild (DW)-type amino acid pattern: arginine, residue 70; leucine, residue 91].
A low aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and low HCV load were independently associated with SVR, but core mutations were not. During follow-up, 12 of 81 (14.8%) patients with the DW-type pattern and 52 of 216 (24.1%) patients with non-DW-type pattern developed HCC (p=0.06, Breslow-Gehan-Wilcoxon test). Multivariate analysis with the Cox proportional-hazards model revealed the following independent risk factors for HCC: male gender [p<0.0001; risk ratio (RR), 3.97], older age (p<0.05; RR, 2.08), advanced fibrosis (p<0.0001; RR, 5.75), absence of SVR (p<0.01; RR, 10.0), high AST level (p<0.01; RR, 2.08), high AST/ALT ratio (p<0.01; RR, 2.21), and non-DW-type pattern (p<0.05; RR, 1.96). In patients with F0-F2 fibrosis at entry, non-DW-type was likely to lead to cirrhosis (p=0.051).
In HCV genotype 1 patients, HCC risk could be predicted by studying core mutations, response to IFN, and host factors like age, gender, and liver fibrosis.
确定丙型肝炎病毒 (HCV) 基因型 1 核心区的氨基酸突变是否与干扰素 (IFN) 治疗反应和肝细胞癌 (HCC) 的发生有关。
我们对 361 例患者（中位随访时间 121 个月）进行了随访，275 例（76%）患者接受了 IFN 单药治疗（持续病毒学应答 (SVR) 率为 26.5%）。使用治疗前血清，分析了核心残基 70 和 91 处的突变[双野（DW）型氨基酸模式：精氨酸，残基 70；亮氨酸，残基 91]。
低天冬氨酸转氨酶 (AST)/丙氨酸转氨酶 (ALT) 比值和低 HCV 载量与 SVR 独立相关，但核心突变无相关性。随访期间，81 例 DW 型患者中有 12 例（14.8%）和 216 例非 DW 型患者中有 52 例（24.1%）发生 HCC（p=0.06，Breslow-Gehan-Wilcoxon 检验）。Cox 比例风险模型多变量分析显示 HCC 的独立危险因素如下：男性（p<0.0001；风险比 [RR]，3.97）、年龄较大（p<0.05；RR，2.08）、纤维化程度较重（p<0.0001；RR，5.75）、无 SVR（p<0.01；RR，10.0）、AST 水平较高（p<0.01；RR，2.08）、AST/ALT 比值较高（p<0.01；RR，2.21）和非 DW 型模式（p<0.05；RR，1.96）。在基线纤维化程度为 F0-F2 的患者中，非 DW 型更可能导致肝硬化（p=0.051）。
在 HCV 基因型 1 患者中，通过研究核心突变、IFN 治疗反应以及年龄、性别和肝纤维化等宿主因素，可预测 HCC 风险。
