Walter Thomas, Dumortier Jérôme, Guillaud Olivier, Hervieu Valérie, Scoazec Jean-Yves, Boillot Olivier
Unité de Transplantation Hépatique-Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Lyon, France.
Liver Transpl. 2007 Feb;13(2):294-301. doi: 10.1002/lt.21000.
Recurrent hepatitis C after liver transplantation (LT) is a major problem, since up to 30% of patients develop cirrhosis only 5 years after LT in the absence of antiviral therapy. The aim of this study was to examine the rate of progression of fibrosis and its associated risk factors in patients submitted to an early antiviral treatment post-LT. Included in the study were 105 patients submitted to LT between September 1990 and December 2004, 70 of whom were treated with interferon and/or ribavirin. A total of 939 liver biopsies were studied. The median fibrosis stage was 0.8 after 1 year post-LT, 1.1 after 3 years, 1.3 after 5 years, and 1.5 after 10 years. LT recipients with fibrosis >2 (13% at 10 years) had a significantly reduced survival rate (63% vs. 87% at 10 years, P = 0.03). Univariate analysis disclosed that recipient male gender, antiviral therapy before LT, LT after 1998, induction immunosuppressive regimen including tacrolimus, induction immunosuppressive regimen including mycophenolate (or without azathioprine), and short duration of prednisolone (<12 months) were significantly associated with progression of fibrosis. In a multivariate analysis, recipient male gender (P = 0.04), antiviral treatment before LT (P = 0.001), and initial immunosuppressive regimen without azathioprine (P = 0.03) were associated with progression of fibrosis. In conclusion, our study has documented that fibrosis progression is not linear over time and that occurrence of severe fibrosis is related to previously described factors related to immunosuppressive regimen or donor age and also to a past history of pre-LT antiviral therapy.
肝移植(LT)后丙型肝炎复发是一个主要问题,因为在未进行抗病毒治疗的情况下,高达30%的患者在肝移植后仅5年就会发展为肝硬化。本研究的目的是检查肝移植后接受早期抗病毒治疗的患者的纤维化进展率及其相关危险因素。该研究纳入了1990年9月至2004年12月期间接受肝移植的105例患者,其中70例接受了干扰素和/或利巴韦林治疗。共研究了939次肝活检。肝移植后1年时纤维化阶段的中位数为0.8,3年后为1.1,5年后为1.3,10年后为1.5。纤维化>2的肝移植受者(10年时为13%)的生存率显著降低(10年时为63%对87%,P = 0.03)。单因素分析显示,受者男性性别、肝移植前的抗病毒治疗、1998年后的肝移植、包括他克莫司的诱导免疫抑制方案、包括霉酚酸酯(或无硫唑嘌呤)的诱导免疫抑制方案以及泼尼松龙使用时间短(<12个月)与纤维化进展显著相关。多因素分析中,受者男性性别(P = 0.04)、肝移植前的抗病毒治疗(P = 0.001)以及初始免疫抑制方案中无硫唑嘌呤(P = 0.03)与纤维化进展相关。总之,我们的研究表明,纤维化进展并非随时间呈线性,严重纤维化的发生与先前描述的与免疫抑制方案或供体年龄相关的因素以及肝移植前抗病毒治疗的既往史有关。