Current Status and Evolving Selection Criteria for Liver Transplant in Treatment of HCC

Liver transplantation (LT) remains the most definitive curative treatment for carefully selected patients with hepatocellular carcinoma (HCC) because it simultaneously removes macroscopic tumor and the cirrhotic field in which de novo carcinogenesis, portal hypertension, and hepatic failure are embedded. The discipline has, however, moved decisively beyond a purely morphometric paradigm. Milan criteria remain the benchmark for transplant legitimacy, but modern selection increasingly integrates alpha-fetoprotein (AFP), AFP kinetics, des-gamma-carboxy prothrombin (DCP/PIVKA-II), AFP-L3, fluorodeoxyglucose positron-emission tomography (FDG-PET), inflammatory indices, response to locoregional therapy (LRT), and emerging radiomic and liquid-biopsy surrogates of occult biologic aggressiveness. Downstaging has similarly evolved from a strategy for list access into a structured biologic stress test. Tumors that can be reduced, stabilized, and biochemically quieted over time are biologically distinct from those that re-progress rapidly despite technical response. This distinction is especially relevant in living donor liver transplantation (LDLT), where reduced waitlist attrition must be balanced against healthy-donor risk and the loss of a prolonged 'test of time'. Contemporary evidence therefore supports a personalized transplant oncology model in which candidacy is judged not by lesion size and number alone but by integrated estimates of recurrence risk, survival benefit, and donor or graft ethics. In parallel, selected patients with portal vein tumor thrombus (PVTT) may now be considered after successful downstaging in expert programs, whereas hepatic vein tumor thrombus (HVTT) remains investigational. The future of LT for HCC will likely be defined by continuous risk modeling that combines morphology, biomarkers, metabolic imaging, molecular residual disease assays, and artificial intelligence within a maturing specialty of transplant oncology.