Guillaud O, Gurram K C, Puglia M, Lilly L, Adeyi O, Renner E L, Selzner N
Multiorgan Transplant Program, and Department of Pathology, University Health Network, University of Toronto, Toronto, ON, Canada.
Transplant Proc. 2013 Jul-Aug;45(6):2331-6. doi: 10.1016/j.transproceed.2013.01.067.
Liver transplantation (LT) for hepatitis C virus (HCV)-related end-stage liver disease is impaired by universal disease recurrence and suboptimal response to antiviral therapy. Inhibition of angiotensin-II signalling by angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin-II receptor blockers (ARB) decreases hepatic stellate cell activation in vitro and hepatic fibrogenesis in animal models. A single-center retrospective analysis suggested that angiotensin blockade (AB) inhibits fibrosis progression in recurrent HCV post-LT. This study assessed the effect of AB on fibrosis progression in an independent patient cohort.
Chart review of all patients who underwent transplantation in our institution for HCV-related ESLD between January 2000 and February 2008 revealed 109 patients with ≥2 protocol liver biopsies and free of antiviral therapy post-LT up to the last biopsy analyzed; 27 of 109 patients were treated with ACE-I/ARB for ≥12 months, 82 were not. Fibrosis was staged using METAVIR.
Live-donor LT was more frequent in controls than in the AB group (25% vs 11%; P < .05). However, parameters known to affect outcome of recurrent HCV, including donor age, prevalence of diabetes, acute cellular rejection, and immunosuppression, were similar in both groups. Time between first and last biopsy (median, 23 months), stage of fibrosis, fibrosis progression rates (median 0.47 vs 0.45 unit/y; P = .46), and time to develop fibrosis stage ≥2 did not differ between groups. Results held true if deceased-donor LT were analyzed separately.
Our study does not support the contention of a previous report that use of AB reduces fibrosis progression in recurrent HCV post-LT.
丙型肝炎病毒（HCV）相关终末期肝病的肝移植（LT）受到普遍的疾病复发和对抗病毒治疗反应欠佳的影响。血管紧张素转换酶抑制剂（ACE-I）或血管紧张素-II受体阻滞剂（ARB）对血管紧张素-II信号传导的抑制作用可在体外降低肝星状细胞的活化，并在动物模型中减少肝纤维化。一项单中心回顾性分析表明，血管紧张素阻断（AB）可抑制LT后复发性HCV的纤维化进展。本研究评估了AB对独立患者队列中纤维化进展的影响。
对2000年1月至2008年2月在本机构接受HCV相关终末期肝病移植的所有患者进行病历审查，发现109例患者有≥2次方案肝活检，且在最后一次分析的活检之前未接受LT后的抗病毒治疗；109例患者中有27例接受ACE-I/ARB治疗≥12个月，82例未接受。使用METAVIR对纤维化进行分期。
活体供肝LT在对照组中比AB组更常见（25%对11%；P <.05）。然而，已知影响复发性HCV结局的参数，包括供体年龄、糖尿病患病率、急性细胞排斥反应和免疫抑制，在两组中相似。两组之间首次和最后一次活检的时间（中位数，23个月）、纤维化分期、纤维化进展率（中位数0.47对0.45单位/年；P =.46）以及发展为纤维化≥2期的时间没有差异。如果对尸体供肝LT进行单独分析，结果仍然成立。
我们的研究不支持先前报告中关于使用AB可降低LT后复发性HCV纤维化进展的观点。
