The incidence of liver diseases, including hepatobiliary cancers, acute liver failure (ALF), and acute-on-chronic liver failure (ACLF), is steadily increasing. Liver transplantation (LT) remains a highly effective treatment for advanced liver disease and liver cancer, but its impact is constrained by graft scarcity and a six-month post-transplant mortality of approximately 10%. Graft allocation relies on statistical models designed to ensure fairness among candidates, yet evolving clinical profiles increasingly challenge their accuracy.

ACLF patients now account for a growing proportion of transplant candidates and are frequently prioritized on waiting lists. However, this population is highly heterogeneous: some patients experience prohibitive short-term mortality despite transplantation, whereas others may recover without LT. These uncertainties raise critical questions regarding transplantation futility and emphasize the need for improved predictive tools to better evaluate individual benefit–risk balance. This challenge is further amplified by expanding LT indications, including the demonstrated survival benefit in patients with colorectal cancer liver metastases reported in the first international randomized trial (Adam, Lancet 2024).

In liver oncology, surgical resection remains the reference treatment, while advances in interventional radiology and medical oncology increasingly promote minimally invasive strategies that aim to improve both survival and quality of life. Across transplantation and cancer care, personalized medicine is essential to identify patients with rapid disease progression, refine surveillance strategies, and optimize treatment timing.

Importantly, liver disease is a systemic condition that frequently affects other organs, particularly the heart and lungs. Liver dysfunction can induce or worsen cardiac and pulmonary impairment, thereby influencing eligibility, peri-procedural risk, and long-term outcomes of liver-directed therapies. Cardiac function is a critical determinant in surgical, radiological, and transplant decision-making, yet predicting cardiac complications related to liver disease or its treatments remains challenging. Conversely, patients with primary cardiac disorders, including congenital heart disease, often develop secondary liver pathology.

These complex liver–heart–lung interactions highlight the need for a holistic, multi-organ approach to personalized liver medicine. Within this framework, temporal regulation also plays a role: disruptions of circadian rhythms have been associated with poorer outcomes in large cancer cohorts, supporting the integration of circadian biomarkers through monitoring. Together, multi-organ integration and time-aware assessment offer a more comprehensive strategy to improve outcomes and reduce complications, particularly in the context of liver transplantation.