Tacrolimus outclasses cyclosporine after liver transplantation for PSC

Tacrolimus appears to be more effective than cyclosporine in improving patient and graft survival after liver transplantation (LT) for primary sclerosing cholangitis (PSC), results of a study have shown.

“[I]n this large propensity score-matched intention-to-treat study with a long-term follow-up, initial tacrolimus treatment was associated with better patient and graft survival than initial cyclosporine treatment in patients undergoing LT for PSC,” the researchers said. “Therefore, tacrolimus should be the standard calcineurin inhibitor (CNI) used after LT for patients with PSC.”

Using the European Liver Transplant Registry (ELTR) and the Scientific Registry of Transplant Recipients (SRTR), the researchers identified adult patients with PSC undergoing a primary LT between 2000 to 2020. Patients initially treated with cyclosporine (n=399) were matched in a 1:3 ratio with those initially treated with tacrolimus (n=1,197) using propensity score. [J Hepatol 2024;80:99-108]

A total of 480 deaths and 231 re-LTs occurred over a median follow-up of 7.4 years. Initial tacrolimus treatment showed better patient and graft survival than cyclosporine, with 10-year patient survival estimates of 72.8 percent for tacrolimus and 65.2 percent for cyclosporine (p<0.001) and 10-year graft survival estimates of 62.4 percent and 53.8 percent (p<0.001), respectively.

These findings persisted in subgroups according to age, sex, registry (ELTR vs SRTR), time period of LT, MELD score, and diabetes status. No significant difference was seen in acute rejection rates between the two treatment groups.

An earlier study also found a slightly improved survival in LT with tacrolimus. [Cochrane Database Syst Rev 2017;3:CD011639]

The use of cyclosporine following LT in patients with PSC was based on the findings of some studies, which included a perception of a reduced risk of recurrent PSC, improved control of frequently coexisting inflammatory bowel disease (IBD), and the association between IBD activity and increased PSC recurrence risk. [Medicine (Baltimore) 2020;99e20205; Clin Gastroenterol Hepatol 2013;11:517-523; Inflamm Bowel Dis 2020;26:1901-1908; JHEP Rep 2022;4100599]

“Although our study does not exclude such potential benefits of cyclosporine over tacrolimus, any differences in this regard between cyclosporine and tacrolimus are likely small, and the fact remains that both patient and graft survival were better with tacrolimus therapy in our study,” the researchers said.

Steroid use

In multivariate analysis, use of tacrolimus (hazard ratio [HR], 0.72; p<0.001) and mycophenolate (HR, 0.82; p=0.03) reduced risk of graft loss or death, but use of steroid did not show a significant effect.

“In exploratory analyses, we observed no benefit of early post-LT steroid use on long-term outcomes,” the researchers said. This finding was consistent with that of previous studies and provided support for steroid-free immunosuppressive regimens for PSC. [J Hepatol 2015;63:1139-1146; Liver Transpl 2003;9:727-732]

“In contrast, we found reduced risks of death and graft loss with the use of mycophenolate or azathioprine, which aligns with findings in more general LT populations,” they added. [Transplantation 2016;100:382-390; Transplantation 2022;106:2182-2192]

“The use of antimetabolites most likely reflects reduced CNI exposure, which may be beneficial for long-term outcomes,” according to the researchers. [Am J Transpl 2012;12:2797-2814; J Hepatol 2013;58:262-270; Am J Transpl 2022;22:1671-1682]