Background: Serial surveillance biopsies demonstrate post-transplant inflammation and fibrosis in long-surviving liver allografts. These findings can lead to cirrhosis and graft failure. We compared two immunosuppressant medications, rapamycin (RAPA) a mTOR inhibitor, and tacrolimus (TAC), a calcineurin inhibitor in a pediatric liver transplant (LTx) population. Recent evidence suggests that RAPA may abrogate liver fibrosis. We hypothesized that mTOR inhibition with RAPA is safe and effective and may improve clinical measures of fibrosis in pediatric LTx recipients.

Methods: Patients who received liver transplants at our institution between 2007 and 2010 were retrospectively identified. Demographics, medications, co-morbities, and laboratory reports from transplant until June 2015 were evaluated. Patients were grouped into those taking TAC and those converted from TAC to RAPA. The reason(s) for conversion and any complications after starting RAPA were noted. For-cause and surveillance liver biopsies were analyzed for rejection using the rejection activity index. Fibrosis score was determined using the METAVIR scoring system.

Results: Of the 20 LTx patients that were evaluated, 12 remained on TAC while 8 underwent conversion from TAC to RAPA. The most common reasons for conversion were renal insufficiency (n=3) and increasing fibrosis (n=2). Of those that remained on TAC, half showed increasing fibrosis since transplant (n=6). Of the patients converted from TAC to RAPA , the majority had decreasing fibrosis after conversion (n=6). In the TAC group, there was an average of 1.1 rejection episodes per 1,000 patient days of therapy. In the RAPA group, there were 0.9 rejection episodes per 1,000 patient days. The most common complications on TAC therapy were infections (n=8) including reactive lymphoid hyperplasia/tonsillitis without PTLD (n=7). The most common complications seen while on RAPA were infections (n=5) and aphthous stomatitis (n=3).

Conclusions: RAPA use may abrogate liver allograft fibrosis over time when compared to TAC maintenance therapy. Patients on RAPA did not experience more rejection episodes than those on TAC after conversion. While a small, heterogenous population of patients makes firm interpretation difficult, we would suggest that RAPA therapy is effective and that future well-controlled trials are necessary.

CITATION INFORMATION: Fischer R, Foster S, Kats A, Andrews W, Hendrickson R, Daniel J. Effect of Conversion to mTOR Inhibition on Allograft Fibrosis in Pediatric Liver Transplantation. Am J Transplant. 2016;16 (suppl 3).

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