Impact of immunosuppression minimization and withdrawal in long-term hepatitis C virus liver transplant recipients

AIM: To investigate the effects of different immunosuppressive regimens and avoidance on fibrosis progression in hepatitis C virus (HCV) liver transplant (LT) recipients. METHODS: 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inhibitors (CNI group, n = 21) and mycophenolate (MMF group, n = 15) monotherapy, with those patients who successfully withdrawn immunosuppression (IS) therapy from at least 3 years (TOL group, n = 10).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. RESULTS: 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. CONCLUSION: IS withdrawal and MMF monotherapy is safe and seems to be associated with the slowest fibrosis progression in HCV LT recipients. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.