Liver transplantation for hepatocellular carcinoma: from patient selection and downstaging to risk stratification and post-transplant surveillance

Liver transplantation (LT) is the most effective curative therapy for selected patients with hepatocellular carcinoma (HCC). However, rising LT demand, limited graft availability, and evolving HCC epidemiology complicate selection of candidate and prediction of pre- and post-LT outcomes. This review summarizes current evidence on patient selection, downstaging strategies, risk stratification, and post-LT surveillance in HCC treated with LT. Recent LT selection criteria increasingly integrate tumor morphology with biological markers and dynamic treatment response. Alpha-fetoprotein (AFP)-based models, such as Metroticket 2.0 and the French AFP criteria, improve prognostication compared with morphology alone. Downstaging using locoregional therapies can effectively decrease a larger tumor burden to LT eligibility criteria, although dropout rates remain higher for patients with larger or 'all-comers' tumors. Immune checkpoint inhibitors (ICIs) show promise for downstaging and may improve post-LT outcomes by eliminating micrometastases, but their rejection risk necessitates a roughly 3-month washout, and further evidence is required before routine use. Risk stratification models combining explant pathology, morphological and biological markers, like RETREAT, MORAL, and emerging tools, like circulating tumor DNA and radiomics/artificial intelligence, allow risk-adaptive surveillance and earlier recurrence detection. Post-LT imaging with AFP monitoring is suggested every 3 to 4 months in year 1, every 6 months in year 2, and every 6 to 12 months in years 3 to 5, with more frequent checks for high-risk patients. Future multicenter prospective studies should standardize downstaging algorithms, establish safe pre-LT ICI protocols, and validate integrated biomarker-imaging surveillance strategies to reduce recurrence and improve graft and patient outcomes.