New England Research Institutes, Inc., Watertown, Massachusetts 02472, USA.
Pharmacogenet Genomics. 2011 Dec;21(12):851-60. doi: 10.1097/FPC.0b013e32834c3e74.
Genetic factors may play a role in fibrosis progression in patients with chronic hepatitis C (CHC). A cirrhosis risk score (CRS7) with seven single nucleotide polymorphisms was previously shown to correlate with cirrhosis in patients with CHC. This study aimed to assess the validity of CRS7 as a marker of fibrosis progression and cirrhosis and as a predictor of clinical outcomes in patients with CHC.
A total of 938 patients (677 Caucasians, 165 African-Americans, and 96 Hispanic/Other) in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial were studied. CRS7 was categorized a priori as high risk (n=440), medium risk (n=310), or low risk (n=188). Patients were assessed for four possible outcomes: fibrosis progression, cirrhosis, clinical outcomes [decompensation or hepatocellular carcinoma (HCC)], or HCC alone.
Twenty-nine percent (142/493) developed an increase in fibrosis score by greater than or equal to 2 points on follow-up biopsies, 58% had cirrhosis on one or more biopsies, 35% developed at least one clinical outcome, and 13% developed HCC. CRS7 (trend test) was associated with risk for fibrosis progression (P=0.04) with adjusted hazard ratio of 1.27 (95% confidence interval: 1.01-1.58) and with cirrhosis (P=0.05) with adjusted odds ratio of 1.19 (1.00-1.41). Rates of HCC and clinical outcomes were increased in patients with higher CRS7 scores, but were not statistically significant (P=0.12 clinical outcomes, and P=0.07 HCC). A single nucleotide polymorphism in AZIN1 was significantly associated with fibrosis progression.
CRS7 was validated as a predictor of fibrosis progression and cirrhosis among Hepatitis C Antiviral Long-term Treatment against Cirrhosis patients, who all had advanced fibrosis. CRS7 was not predictive of clinical outcome.
遗传因素可能在慢性丙型肝炎（CHC）患者的纤维化进展中发挥作用。先前已证明，包含七个单核苷酸多态性的肝硬化风险评分（CRS7）与 CHC 患者的肝硬化相关。本研究旨在评估 CRS7 作为纤维化进展和肝硬化标志物以及 CHC 患者临床结局预测因子的有效性。
对慢性丙型肝炎抗病毒长期治疗预防肝硬化试验中的 938 例患者（677 例白种人、165 例非裔美国人、96 例西班牙裔/其他族裔）进行了研究。CRS7 预先分为高危（n=440）、中危（n=310）和低危（n=188）。评估患者的四种可能结局：纤维化进展、肝硬化、临床结局（失代偿或肝细胞癌（HCC））或 HCC 单独发生。
29%（493 例中有 142 例）在随访活检中纤维化评分增加≥2 分，58%在一次或多次活检中出现肝硬化，35%出现至少一种临床结局，13%发生 HCC。CRS7（趋势检验）与纤维化进展风险相关（P=0.04），调整后的危险比为 1.27（95%置信区间：1.01-1.58），与肝硬化相关（P=0.05），调整后的比值比为 1.19（1.00-1.41）。高 CRS7 评分患者的 HCC 和临床结局发生率增加，但无统计学意义（P=0.12 临床结局，P=0.07 HCC）。AZIN1 中的一个单核苷酸多态性与纤维化进展显著相关。
CRS7 在慢性丙型肝炎抗病毒长期治疗预防肝硬化试验中得到验证，可预测纤维化进展和肝硬化，所有患者均有晚期纤维化。CRS7 不能预测临床结局。
