Warning over sirolimus in HCV-positive liver transplantation

Sirolimus, whether given at the time of liver transplantation (LT) or after, is associated with poorer outcomes in patients with hepatitis C virus (HCV) infection compared with those who do not take the immunosuppressant, shows a US study.

The findings help provide important information on the controversial use of mammalian target of rapamycin (mTOR) inhibitors as primary immunosuppressants after LT.

"The results of this analysis suggest that mTOR inhibitors should be used with great caution in LT recipients with HCV infections," write Michael Charlton (Mayo Clinic and Foundation, Rochester, Minnesota, USA) and colleagues in Liver Transplantation.

The study included 26,414 transplant patients, included in the Scientific Registry of Transplant Recipients. Overall, 12,589 had an underlying HCV infection and sirolimus was prescribed at discharge in 1685 patients. Patients were followed up at 6 months and annually thereafter.

Multivariate analysis showed that patients with HCV were 26% more likely to die within 3 years if they were given sirolimus at discharge compared with those who were not. However, in HCV-negative patients, there was no significant association between sirolimus and risk for mortality.

In comparison, the calcineurin inhibitor, tacrolimus was associated with a 26% reduction in the risk of 3-year mortality in HCV-positive patients and a 44% reduction in HCV-negative patients.

To minimize the likelihood that their findings were due to sirolimus being prescribed in the most high-risk patients, the authors conducted a propensity analysis, controlling for factors known to affect posttransplant survival. However, the influence of sirolimus on 3-year mortality persisted.

The authors also found that patients taking sirolimus for longer than a year and those that began treatment more than a year after surgery had reduced survival compared with those who took the immunosuppressant immediately after surgery but for less than a year.

In an accompanying editorial, Parul Agarwal and Michael Lucey (University of Wisconsin, Madison, USA) say that the study "sounds an important note of warning regarding the use of mTOR inhibitors in HCV-infected LT recipients."

However, they caution that the study has significant limitations and say that further research is needed.

"A greater understanding of the relative impact of available immunosuppressive agents on key posttransplant outcomes is one of the most pressing needs of the LT community," the authors concur.

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