What are the major challenges in liver transplantation today?

The demand for organs far outstrips the donation rates in liver transplantation. The costs are high, and there are significant regional disparities, leading to delayed referral and inequity in access to transplant programs and post-operative care. The burden of liver diseases includes the need for transplantation for very sick patients at risk of high short-term mortality, such as acute-on-chronic liver failure (ACLF), which remains a major cause of death while on the waitlist. Liver transplantation is the only curative treatment for patients with ACLF. However, its applicability is challenging due to the timely selection of candidates, high short-term risks, and the limited accuracy of the model for end-stage liver disease (MELD) score in predicting mortality related to multiple organ failures. Furthermore, organ allocation policies and regulations vary across the world, with marked regional differences. In addition, current criteria do not take into account variations in mortality related to racial and genetic ancestry, as recently demonstrated in the ACLARA study. Despite these drawbacks, ACLF, and particularly ACLF-3, should not be considered a contraindication for liver transplantation. Recent studies have demonstrated that ACLF patients have good post-transplant survival rates. However, ACLF-3 patients were shown to have greater use of hospital resources and a longer hospital stay. Clearly, there is room for more studies and granular data. In the era of precision medicine, it is hoped that new markers may help improve the criteria for patient selection.