A retrospective 15-year review: survival advantage after switching to sirolimus in hepatitis C virus infected liver graft recipients

BackgroundThe use of sirolimus-based immune suppression in liver transplantation, particularly in hepatitis C virus (HCV)-infected recipients, remains contentious. There is some evidence that sirolimus retards hepatic fibrosis, is renal sparing and may be of benefit in preventing hepatocellular carcinoma (HCC) recurrence. Sirolimus has not been adopted by many transplant centres because of persistent concerns regarding an increased risk of hepatic artery thrombosis, graft loss and death with de novo sirolimus. AimTo review the impact of switching to sirolimus monotherapy in HCV-infected liver recipients with respect to survival, graft loss and hepatic fibrosis. MethodsA retrospective review of 190 patients from a single centre undergoing first liver transplantation for HCV over 15years. 113 patients were switched from calcineurin inhibitor (CNI)-based therapy to low-dose sirolimus monotherapy at a median of 15months after transplantation for HCV-related fibrosis (72%), renal impairment (14%) or high-risk HCC (5%). ResultsPatients switched to sirolimus had improved survival (P<0.001) and slower progression to cirrhosis (P=0.001). In patients with HCC (n=91), sirolimus duration rather than strategy was an independent predictor of survival (P=0.001) and extended time to HCC recurrence (33 vs. 16months). Patients switched for renal dysfunction showed improvement in serum creatinine (140-108mol/L, P=0.001). Those remaining on CNI-therapy were more likely to develop post-transplant diabetes (P=0.03). ConclusionThese data suggest selective switching to low-dose sirolimus monotherapy in HCV-positive liver recipients improves clinical outcome.