肝移植后复发性丙型肝炎的抗病毒治疗：应答预测因子和长期结局。

Antiviral treatment of recurrent hepatitis C after liver transplantation: predictors of response and long-term outcome.

机构信息

Multi-organ Transplant Program, University Health Network, University of Toronto, Toronto, ON, Canada.

出版信息

Transplantation. 2009 Nov 27;88(10):1214-21. doi: 10.1097/TP.0b013e3181bd783c.

DOI:10.1097/TP.0b013e3181bd783c

PMID:19935376

Abstract

BACKGROUND

Efficacy and long-term outcome of antiviral therapy for recurrent hepatitis C after liver transplantation is poorly defined.

AIM

This study aimed at assessing the efficacy of antiviral therapy regarding sustained hepatitis C virus (HCV) clearance, liver histology, and patient survival.

METHODS

We retrospectively reviewed all 446 patients who received a liver allograft at our institution for HCV-related cirrhosis between January 1992 and December 2006. Two hundred thirty-two patients (52%) were eligible for antiviral therapy based on predefined criteria (Metavir stage > or =1 and/or grade > or =2; protocol biopsies). One hundred seventy-two patients (39%) had no contraindication for treatment, received more than or equal to 1 dose of interferon-alpha-based combination therapy, and form the basis of this analysis. Therapy was aimed for 48 weeks; median posttreatment follow-up was 68 months.

RESULTS

The overall sustained virological response (SVR) rate was 50% (genotype 1/4: 40%; genotype 2/3: 76%). SVR was higher on cyclosporine A (CsA) (56%) than on tacrolimus (44%, P=0.05), largely because of a lower relapse rate (6% vs. 19%, P=0.01). In multivariate analysis, genotype 2/3, CsA use, donor age, and pretreatment necroinflammatory activity were independently associated with SVR. SVR significantly improved histology and long-term survival (actuarial 5-year survival 96% vs. 69% in nonresponders, P<0.0001).

CONCLUSION

Antiviral therapy of recurrent hepatitis C after liver transplantation is able to clear HCV in half the patients, more likely on CsA than on tacrolimus, and markedly improves outcome.

摘要

背景

肝移植后复发丙型肝炎的抗病毒治疗效果和长期预后仍不清楚。

目的

本研究旨在评估抗病毒治疗对持续清除丙型肝炎病毒（HCV）、肝组织学和患者生存的疗效。

方法

我们回顾性分析了 1992 年 1 月至 2006 年 12 月期间在我院接受肝移植的 446 例丙型肝炎相关肝硬化患者。根据预先确定的标准（Metavir 分期>或=1 级和/或分级>或=2 级；方案活检），232 例患者（52%）适合抗病毒治疗。172 例患者（39%）无治疗禁忌证，接受了至少 1 剂干扰素-α联合治疗，是本分析的基础。治疗目标为 48 周；中位治疗后随访时间为 68 个月。

结果

总体持续病毒学应答（SVR）率为 50%（基因型 1/4：40%；基因型 2/3：76%）。环孢素 A（CsA）组（56%）的 SVR 高于他克莫司（Tac）组（44%，P=0.05），主要是因为复发率较低（6%对 19%，P=0.01）。多变量分析显示，基因型 2/3、CsA 应用、供者年龄和治疗前坏死性炎症活动与 SVR 独立相关。SVR 显著改善了组织学和长期生存（无应答者的 5 年生存率分别为 96%和 69%，P<0.0001）。