American Journal of Transplantation, 2011. McKenna et al.
Sirolimus is used in post-transplant immunosuppression. Since it is not part of the calcineurin inhibitor (CNI) family like tacrolimus and cyclosporin, it is often used in cases of CNI nephrotoxicity or intolerance. Furthermore, it is thought to have properties that delay progression of fibrosis in HCV and prevent neoangiogenesis in cases of hepatocellular carcinoma.
This article followed two arms of liver transplant recipients: control arm with a cacineurin inhibitor (n=282) and a study arm (n=173) with early sirolimus initiation. It is readily apparent that the two arms are not equal from the outset: the control arm had a significantly higher MELD score (ie. sicker patient) and far fewer patients with hepatocellular carcinoma.
The authors designed the figures in such a way that demonstrated a central theme- that after two years of follow-up, cumulative fibrosis is inversely correlated with the total duration of sirolimus exposure. This finding, however, was misleading. If one were to re-analyze the data and group sirolimus-exposed patients into discrete groups (ie. received the drug for 0-3 months, 3-12 months, >12 months) the cumulative rate of fibrosis remains statistically unchanged.
Therefore, while sirolimus may have beneficial effects on fibrosis progression in HCV (and perhaps even HCC recurrence), this article did not convince us of such.