The Emerging Challenge of Non-Cirrhotic MASLD-Related Hepatocellular Carcinoma: Etiology, Immunopathology, and Precision Oncology

Non-cirrhotic MASLD-HCC is a distinct oncogenic entity driven by metabolic-immune interplay. Its recognition necessitates a shift in clinical paradigm: (1) surveillance strategies must incorporate metabolic and genetic risk factors beyond cirrhosis; (2) the unique TME may predict immunotherapy efficacy, urging etiology-specific trial design; and (3) a precision oncology framework integrating molecular subtyping and biomarker profiling is essential for early detection and tailored management of this growing patient population.