Work

An evaluation of the safety and preliminary efficacy of peri‐ and post‐operative treprostinil in preventing ischemia and reperfusion injury in adult orthotopic liver transplant recipients

Year: 2021

Type: article

Abstract: Background Orthotopic liver transplantation (OLT) is the only treatment option for various end‐stage liver diseases. Ischemia and reperfusion (I/R) injury is one of the unavoidable complications/conditions in OLT. In 2019, a total of 8896 livers were transplanted of which >94% organs were procured from deceased donors. An increase in the use of extended criteria donor (ECD) livers for transplantation further unraveled the role of hepatic I/R injury on short‐term and long‐term graft outcomes. Despite promising outcomes with the use of antioxidants, free radical scavengers, and vasodilators; I/R‐mediated liver injury persists and significantly influences the overall clinical outcomes. Treprostinil, a synthetic prostacyclin I2 (PGI2) analog, due to its vasodilatory property, antiplatelet activity, and its ability to downregulate pro‐inflammatory cytokines can potentially minimize I/R injury. Aim We investigated the safety and preliminary efficacy of continuous intravenous infusion of treprostinil in liver transplant recipients in a prospective, single‐center, non‐randomized, interventional study. Material and methods This was a dose escalation (3 + 3 design) phase 1/2 study. Deceased donor liver transplant recipients received 5 ng/kg/min for two days, or 2.5, 5, and 7.5 ng/min/kg for 5 days as a continuous infusion. Multiple blood samples were collected for biochemical parameter assessment and for measuring treprostinil levels. Indocyanine green plasma disappearance rate was used as a measure of hepatic functional capacity. Results Subjects tolerated continuous infusion of treprostinil up to 5 ng/kg/min for 120 h with no occurrence of primary graft non‐function (PNF), minimized need for ventilation support, reduced hospitalization time, 100% graft and patient survival, and improved hepatobiliary excretory function comparable to normal healthy adults. Discussion Treprostinil can be administered to liver transplant patients safely during the perioperative period. Conclusion Based on this phase 1/2 study, further efficacy studies of treprostinil in preventing I/R injury of liver should be conducted to potentially increase the number of livers available for transplantation.

Source: Clinical Transplantation

DOI: 10.1111/ctr.14298