Liver transplantation in Japan: Achievements, limitations, and future perspectives.

Liver cirrhosis (LC) represents a substantial and growing global health burden, driving high mortality through liver failure and hepatocellular carcinoma (HCC), for which liver transplantation (LT) remains the only definitive and life-saving therapy. Despite continuous technical and perioperative advances, a critical unmet need persists due to the imbalance between organ demand and availability. In Japan, the practice of LT is uniquely shaped by the predominance of living donor transplantation and a marked epidemiological transition: the burden of viral hepatitis-related cirrhosis has declined with antiviral therapies, while metabolic dysfunction-associated steatohepatitis (MASH) and alcohol-associated liver disease (ALD) are emerging as leading indications. This paradigm shift necessitates refinement of transplant strategies, including improved candidate selection for HCC through integration of tumor biology and novel biomarkers and careful consideration of immunotherapy-related risks. Moreover, MASH introduces complex challenges related to obesity, disease recurrence, and the role and timing of metabolic interventions, whereas ALD raises ongoing clinical and ethical questions regarding early transplantation and relapse prevention. Future progress will depend on expanding the donor pool through innovations such as machine perfusion and xenotransplantation as well as expanding indications to selected non-HCC malignancies and adopting advanced surgical technologies. Collectively, LT is transitioning toward a precision-based, multidisciplinary, and innovation-driven paradigm.