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Minimal immunosuppression recommended in transplant setting

AMSTERDAM — Understanding the impacts of fibrosis, drug–drug interactions with direct-acting antiviral therapies, and the pitfalls of immunosuppression can aid clinicians in treating liver transplantation candidates or recipients, according to data presented at the International Liver Congress.

Michael Charlton, MD, a transplant hepatologist and director of the Intermountain Transplant and Regenerative Medicine Center, said that the frequency of wait-listing for transplantation for patients with HCV has decreased considerably in recent years. “The indication is now highest for alcohol use,” he said. “The indications for NASH have remained relatively stable.”

Charlton reviewed data from the SOLAR-1 and SOLAR-2 studies, which included transplant and non-transplant patients. The findings indicated a decline in SVR with the increase in Child-Pugh score. “Child-Pugh A and B were fine, but not Child-Pugh C,” he said. “I don’t think we will see another study like it in the post-transplant setting.”

He noted that levels of triphosphate forged by sofosbuvir may be associated with progression of disease.

Findings from the ASTRAL study showed that the lowest relapse rates were reported in the ribavirin-containing arm, according to Charlton. “The transplant setting behaves similarly as the relapse setting,” he said.

An important take-home message from the LONESTAR study is that sofosbuvir plus an NS5A inhibitor and ribavirin may be an optimal regimen after transplantation, according to Charlton.

He added that while novel DAA therapies are not known for drug–drug interactions, one particular association involves OATP1B1/3 and CYP2C8. DAA’s may be the “victims” or the “culprits” in DAA-associated drug–drug interactions, and Charlton recommended that clinicians be aware of potential concerns. “Overall, [drug–drug interactions] with these drugs are numerous and complex, but the most important one is simeprevir and cyclosporine, and possibly sofosbuvir and cyclosporine,” he said.

Regarding the choice between tacrolimus and cyclosporine, Charlton suggested there was no difference in terms of overall survival for all transplant patients, but that tacrolimus had superior survival in HCV patients compared with cyclosporine. He stressed that clinicians should be aware of calcineurinia after SVR. “Tacrolimus may be the optimal calcineurin inhibitor for HCV,” he said. “A minimally necessary approach to overall immunosuppression should be considered.” – by Rob Volansky

Reference: Charlton M. PGC on Liver Transplantation: Liver transplantation for viral hepatitis. Presented at: International Liver Congress; April 19-24, 2017; Amsterdam.

Disclosure: Charlton reports receiving grant or research support from AbbVie, Gilead Sciences, Intercept, Janssen, Merck and Novartis as well as consulting for Gilead Sciences.