Manzia Tommaso Maria, Angelico Roberta, Ciano Paolo, Mugweru Jon, Owusu Kofi, Sforza Daniele, Toti Luca, Tisone Giuseppe
Tommaso Maria Manzia, Roberta Angelico, Paolo Ciano, Daniele Sforza, Luca Toti, Giuseppe Tisone, Department of Experimental Medicine and Surgery, Section of Transplantation, Tor Vergata University of Rome, 00133 Rome, Italy.
World J Gastroenterol. 2014 Sep 14;20(34):12217-25. doi: 10.3748/wjg.v20.i34.12217.
To investigate the effects of different immunosuppressive regimens and avoidance on fibrosis progression in hepatitis C virus (HCV) liver transplant (LT) recipients.
We retrospectively compared the liver biopsies of well-matched HCV LT recipients under calcineurin inhibitors (CNI group, n = 21) and mycophenolate (MMF group, n = 15) monotherapy, with those patients who successfully withdrawn immunosuppression (IS) therapy from at least 3 years (TOL group, n = 10). To perform the well-matched analysis, all HCV transplanted patients from December 1993 were screened. Only those HCV patients who reached the following criteria were considered for the analysis: (1) at least 3 years of post-operative follow-up; (2) patients with normal liver graft function under low dose CNI monotherapy (CNI group); (3) patients with normal liver graft function under antimetabolite (Micophenolate Mofetil or coated mycophenolate sodium) monotherapy (MMF group); and (4) recipients with normal liver function without any IS. We excluded from the analysis recipients who were IS free or under monotherapy for < 36 mo, recipients with cirrhosis or with unstable liver function tests.
Thirty six recipients were enrolled in the study. Demographics, clinical data, time after LT and baseline liver biopsies were comparable in the three groups. After six years of follow-up, there was no worsening of hepatic fibrosis in the MMF group (2.5 ± 1.5 Ishak Units vs 2.9 ± 1.7 Ishak Units, P = 0.5) and TOL group (2.7 ± 10.7 vs 2.5 ± 1.2, P = 0.2). In contrast, a significant increase in the fibrosis score was observed in the CNI group (2.2 ± 1.7 vs 3.9 ± 1.6, P = 0.008). The yearly fibrosis progression rate was significantly worse in the CNI group (0.32 ± 0.35) vs MMF group (0.03 ± 0.31, P = 0.03), and TOL group (-0.02 ± 0.27, P = 0.02). No differences have been reported in grading scores for CNI group (2.79 ± 1.9, P = 0.7), MMF group (3.2 ± 1.5, P = 0.9) and TOL group (3.1 ± 1.4, P = 0.2). Twenty four patients were treated with low dose ribavirin (8 TOL, 7 MMF, 9 CNI). The hepatitis C titers were comparable in the three groups. No episodes of rejection have been reported despite differences of liver function test in the three groups during the observational period.
IS withdrawal and MMF monotherapy is safe and seems to be associated with the slowest fibrosis progression in HCV LT recipients.
研究不同免疫抑制方案及停用免疫抑制剂对丙型肝炎病毒（HCV）肝移植（LT）受者纤维化进展的影响。
我们回顾性比较了接受钙调神经磷酸酶抑制剂治疗（CNI组，n = 21）和霉酚酸治疗（MMF组，n = 15）的匹配良好的HCV LT受者的肝活检情况，以及那些成功停用免疫抑制（IS）治疗至少3年的患者（TOL组，n = 10）。为进行匹配良好的分析，我们筛查了1993年12月以来所有的HCV移植患者。只有达到以下标准的HCV患者才被纳入分析：（1）术后至少随访3年；（2）低剂量CNI单药治疗下肝移植功能正常的患者（CNI组）；（3）抗代谢药物（吗替麦考酚酯或肠溶型霉酚酸钠）单药治疗下肝移植功能正常的患者（MMF组）；（4）无任何IS且肝功能正常的受者。我们将未使用IS或单药治疗时间<36个月的受者、患有肝硬化或肝功能检查不稳定的受者排除在分析之外。
36名受者被纳入研究。三组在人口统计学、临床数据、肝移植后时间和基线肝活检方面具有可比性。随访6年后，MMF组（2.5±1.5 Ishak单位 vs 2.9±1.7 Ishak单位，P = 0.5）和TOL组（2.7±10.7 vs 2.5±'1.2'，P = 0.2）的肝纤维化没有恶化。相比之下，CNI组的纤维化评分显著增加（2.2±1.7 vs 3.9±1.6，P = 0.008）。CNI组的年度纤维化进展率明显高于MMF组（0.32±0.35 vs 0.03±0.31，P = 0.03）和TOL组（-0.02±0.27，P = 0.02）。CNI组（2.79±1.9，P = 0.7）、MMF组（'3.2±1.5'，P = 0.9）和TOL组（3.1±1.4，P = 0.2）的分级评分没有差异。24名患者接受了低剂量利巴韦林治疗（8名TOL组患者、7名MMF组患者、9名CNI组患者）。三组的丙型肝炎病毒滴度具有可比性。尽管观察期内三组的肝功能检查存在差异，但均未报告排斥反应事件。
停用IS和MMF单药治疗是安全的，并且似乎与HCV LT受者中最慢的纤维化进展相关。
