干扰素 lambda-3 与 HCV 诱导的代偿性肝硬化患者的临床结局无关：一项长期队列研究。

Interferon lambda-3 is not associated with clinical outcome in patients with HCV-induced compensated cirrhosis: a long-term cohort study.

机构信息

Department of Internal Medicine, A.O. Fatebenefratelli e Oftalmico, Milan, Italy.

Department of Gastroenterology, St Vincent's Hospital, The University of Melbourne, VIC, Australia; Department of Medicine, St Vincent's Hospital, The University of Melbourne, VIC, Australia; Duke Clinical Research Institute and Department of Gastroenterology, Duke University, Durham, NC, USA.

出版信息

Antiviral Res. 2015 Jan;113:27-32. doi: 10.1016/j.antiviral.2014.11.002. Epub 2014 Nov 11.

DOI:10.1016/j.antiviral.2014.11.002

PMID:25446338

Abstract

BACKGROUND

Interferon Lambda-3 (IFN-λ3) gene polymorphism is associated with spontaneous clearance of hepatitis C virus (HCV) and response to IFN-based therapy (IFN). However, very few data are available about its value in predicting sustained virologic response (SVR) in patients with cirrhosis, and whether IFN-λ3 genotype influences liver disease progression remains unclear.

METHODS

We determined IFN-λ3 genotype by PCR in a cohort of patients with compensated HCV-related cirrhosis, enrolled between 1989 and 1992. Person-years follow-up was calculated for each individual from the date of enrolment to the development of first episode of decompensation, HCC, liver transplant, death or end of follow-up. The follow-up of patients who achieved SVR was censored at the time of IFN initiation. Kaplan-Meier curves and Cox regression analyses were used to assess the association between IFN-λ3 genotype and clinical outcome.

RESULTS

IFN-λ3 was determined in 264 patients (52% males, mean age 57±8 years, 67% HCV genotype (G)1, while CC, CT and TT genotypes were 36%, 50% and 14%, respectively. During a median follow-up of 14.8 years, 149 (56%) patients received IFN. Overall, SVR was achieved in 31 (21%) patients, 40% among those with CC genotype (22% in G1 and 61% in G2, respectively) compared to 10% and 13% among patients with CT and TT genotypes (p<0.0001). Univariate and multivariate analyses found no association between IFN-λ3 (CC vs. non-CC genotype) and disease progression.

CONCLUSION

IFN-λ3 determination is fundamental for allocating cirrhotic patients to be treated with IFN, while it has no value in predicting the outcome of the disease.

摘要

背景

干扰素 Lambda-3（IFN-λ3）基因多态性与丙型肝炎病毒（HCV）的自发清除和基于干扰素的治疗（IFN）反应有关。然而，关于其在预测肝硬化患者持续病毒学应答（SVR）中的价值以及 IFN-λ3 基因型是否影响肝病进展的数据非常有限。

方法

我们通过聚合酶链反应（PCR）在 1989 年至 1992 年间招募的代偿性 HCV 相关肝硬化患者队列中确定了 IFN-λ3 基因型。从每位患者的入组日期到首次失代偿、肝细胞癌（HCC）、肝移植、死亡或随访结束，计算个体的人年随访时间。达到 SVR 的患者的随访时间在开始 IFN 治疗时截止。使用 Kaplan-Meier 曲线和 Cox 回归分析评估 IFN-λ3 基因型与临床结局之间的关系。

结果

在 264 例患者（52%为男性，平均年龄 57±8 岁，67%为 HCV 基因型（G）1，而 CC、CT 和 TT 基因型分别为 36%、50%和 14%。在中位随访 14.8 年期间，149 例（56%）患者接受了 IFN。总的来说，31 例（21%）患者获得了 SVR，CC 基因型患者的 SVR 率为 40%（G1 为 22%，G2 为 61%），而 CT 和 TT 基因型患者的 SVR 率分别为 10%和 13%（p<0.0001）。单因素和多因素分析均未发现 IFN-λ3（CC 与非 CC 基因型）与疾病进展之间存在关联。