纤维化进展受环境和宿主因素影响，是慢性丙型肝炎（CHC）肝脏疾病结局的主要决定因素。最近提出一项由7个单核苷酸基因多态性组成的肝硬化危险评分（CRS）作为丙型肝炎后肝硬化的基因预测因子。为了评估CRS在预测无纤维化、轻度或中度纤维化患者的纤维进展中的作用，我们调查了271例未经治疗的CHC患者，他们初始肝活检显示其METAVIR分期为F0（n=104）、F1（n=101）和F2（n=59）,并且他们至少60个月内未行抗病毒治疗（平均108.5±71.5个月），在此项观察结束时再次行肝活检。24.2%的人未显示组织学进展，75.6%的人进展至少一个METAV2R分期，45.0%的人进展至少两个分期，10.3%的人进展两个分期以上。有纤维化进展的患者平均CRS分数比没有纤维化进展的明显增高（p=0.005），并且这种差异在初始肝活检为F0期的患者中尤为明显。平均CRS分数与纤维化进展程度不相关。纤维化进展的相对危险随着CRS分数增加而增加。这种相关性在女性中不显著，在男性中显著，在初始肝活检为F0期的高CRS分值的男性患者中最为显著（OR=16.5,95%CI 1.6-166；p=0.02）。多因素分析证实了CRS分值与纤维化进展的显著关系。CRS在摄入大量酒精的CHC患者中的预测价值也得到证实。结果：CRS相关宿主基因可预测初始轻度CHC男性患者的纤维化进展，并且可能成为预后评估和治疗决策的有用参数。
吉林大学第一医院肝胆胰内科 陈林娇 摘译
本文首次发表于[Hepatology, 2009, 50(4):1038-1044]
A Seven-Gene Signature (Cirrhosis Risk Score) Predicts Liver Fibrosis Progression in Patients with Initially Mild Chronic Hepatitis C
Abstract：Fibrosis progression is the main determinant of liver disease outcome in chronic hepatitis C, being influenced by environmental and host factors. Recently, a cirrhosis risk score (CRS) based on seven single-nucleotide polymorphisms was proposed as genetic predictor of cirrhosis in hepatitis C. To assess the role of CRS in predicting fibrosis progression in patients with initially no or minimal to moderate fibrosis, we investigated 271 untreated patients with chronic hepatitis C having initial liver biopsy showing METAVIR stage F0 (n = 104), F1 (n = 101), or F2 (n = 59) who had been followed up without antiviral therapies for at least 60 months (mean 108.5 +/- 71.5 months) and had a liver biopsy at the end of this observation period. Of these, 24.4% showed no histologic progression, 75.6% progressed by at least one stage, 45.0% progressed by at least two stages, and 10.3% progressed by more than two stages. The mean CRS was significantly higher (P = 0.005) in patients with fibrosis progression compared with those without progression, and this difference was particularly evident (P = 0.002) with F0 on initial biopsy. Mean CRS scores were not associated with degree of fibrosis progression. The relative risk of fibrosis progression increased with increasing CRS values. This association was significant in males but not in females and was most evident in males with F0 at initial biopsy (odds ratio 16.5, 95% confidence interval 1.6-166; P= 0.02) in the presence of high CRS. Multivariate analysis confirmed the significant association of CRS score with fibrosis progression. The predictive value of CRS was confirmed in hepatitis C virus patients admitting significant alcohol intake. Conclusion: Host genetics defined by CRS predict fibrosis progression in males with initially mild chronic hepatitis C and may become a useful parameter for prognostic evaluation and treatment decision.
