Liver transplantation is the treatment of choice for patients with acute and chronic end-stage liver disease including acute liver failure, decompensated cirrhosis and hepatocellular carcinoma (HCC) (Lucey et al., 2013).
Cirrhosis is the leading indication for liver transplantation as shown in the figure below. The most common causes of liver cirrhosis are viruses (40%) and alcohol (33%) (European Association for the Study of the Liver (EASL), 2013).
Meanwhile, in the U.S., the most common indications for adult liver transplantation in 2015 were hepatitis C virus (22.7%), alcoholic liver disease (21.0%) and malignancy (18.7%) (Kim et al., 2017).
Improvements in immunosuppressive regimens and surgical techniques has substantially improved transplant outcomes. Between 1987 and 2013 there was a two-fold decrease in 1-year graft loss and a 1.6-fold decrease in 5-year graft loss (Stepanova et al., 2015). Calcineurin inhibitors were a key development in the improvement of graft survival, however, their long-term use is also associated with significant complications – in particular CNI-related nephrotoxicity leading to progressive renal deterioration (Morard et al., 2006). Calcineurin-inhibitor sparing regimens are being investigated as an alternative treatment option that maintain immunosuppression, but with reduced renal damage.