Assessment of chronic rejection in liver graft recipients receiving immunosuppression with low-dose calcineurin inhibitors

Abstract

Background & aims: Calcineurin inhibitors represent the cornerstone immunosuppressants after liver transplantation despite their side effects. As liver graft is particularly well tolerated, low doses may be proposed. The aim of this study was to assess the prevalence of chronic rejection in patients with low calcineurin inhibitors regimen and to compare their characteristics with patients under standard doses.

Methods: All patients with liver transplantation between 1997 and 2004 were divided into two groups. Low-dose patients (n=57) had tacrolimus baseline levels <5ng/ml or cyclosporine levels <50ng/ml at t0 or <100ng/ml at t+2h and were prospectively proposed a liver biopsy, searching for chronic rejection according to Banff criteria. The remaining patients constituted the standard-doses group (n=40).

Results: Among the low-dose group, 36 patients in the low-dose group were assessed by biopsy. No chronic rejection was found. Fifty-six percent had only calcineurin inhibitors and 8% received other immunosuppressants only. The median time between liver transplantation and biopsy was 90 months (64-157) and between IS regimen decrease and biopsy was 41 months (11-115). Liver tests were normal in 72% of the patients. Low-dose patients had more often hepatitis B (p=0.045), less past acute rejection episodes (p=0.028), and better renal function (p=0.040). Decrease of calcineurin inhibitors failed in 15% of standard-dose patients without impacting the graft function. In the low-dose group, co-prescription of other immunosuppressants facilitated the decrease (p=0.051).

Conclusions: The minimization, or even cessation, of calcineurin inhibitors may be an achievable goal in the long term for most of the liver graft recipients.

Keywords: Biopsy; CNI; Graft rejection; HBV; HCV; Immunosuppressive agents; LD; LFT; LT; Liver transplantation; MMF; SD; Transplantation tolerance; calcineurin inhibitors; hepatitis B virus; hepatitis C virus; liver function test; liver transplantation; low-dose; mTOR; mammalian target of rapamycin; mycophenolate mofetil; standard-dose.