title: A retrospective 15-year review: survival advantage after switching to sirolimus in hepatitis C virus infected liver graft recipients.
abstract: BACKGROUND
  The 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.
  
  
  OBJECTIVE
  To review the impact of switching to sirolimus monotherapy in HCV-infected liver recipients with respect to survival, graft loss and hepatic fibrosis.
  
  
  METHODS
  A retrospective review of 190 patients from a single centre undergoing first liver transplantation for HCV over 15 years. 113 patients were switched from calcineurin inhibitor (CNI)-based therapy to low-dose sirolimus monotherapy at a median of 15 months after transplantation for HCV-related fibrosis (72%), renal impairment (14%) or high-risk HCC (5%).
  
  
  RESULTS
  Patients 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. 16 months). Patients switched for renal dysfunction showed improvement in serum creatinine (140-108 μmol/L, P = 0.001). Those remaining on CNI-therapy were more likely to develop post-transplant diabetes (P = 0.03).
  
  
  CONCLUSIONS
  These data suggest selective switching to low-dose sirolimus monotherapy in HCV-positive liver recipients improves clinical outcome.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge University Hospitals, Cambridge, UK.
authors.forename: M
authors.initials: M
authors.lastname: Shah
authors.forename: A
authors.initials: A
authors.lastname: Shankar
authors.forename: I
authors.initials: I
authors.lastname: Gee
authors.forename: K
authors.initials: K
authors.lastname: Nash
authors.forename: M
authors.initials: M
authors.lastname: Hoare
authors.forename: P
authors.initials: P
authors.lastname: Gibbs
authors.forename: S
authors.initials: S
authors.lastname: Davies
authors.forename: G J M
authors.initials: GJ
authors.lastname: Alexander
mesh_terms: D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control; D015897:Comorbidity; D018450:Disease Progression; D005260:Female; D016174:Hepacivirus; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000517:prevention & control; D008113:Liver Neoplasms / Q000517:prevention & control; D016031:Liver Transplantation / Q000379:methods* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000139:chemically induced; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D020123:Sirolimus