ABSTRACT Background and Aims Hepatic steatosis often diminishes as metabolic dysfunction–associated steatotic liver disease (MASLD) progresses, leading to a so‐called ‘burnt‐out’ state. Whether this phenotype simply reflects advanced liver injury or represents a biologically distinct condition with prognostic relevance after hepatocellular carcinoma (HCC) development remains unclear. We evaluated the clinical significance of burnt‐out MASLD in patients undergoing curative resection for MASLD‐related HCC. Methods In this retrospective, pathology‐confirmed cohort of patients who underwent curative‐intent hepatectomy for MASLD‐related HCC ( n = 931), concurrent histologic assessment of steatosis (S) and fibrosis (F) was used to define four phenotypes: S > 1/F 1/F ≥ 3 and burnt‐out MASLD (S ≤ 1/F ≥ 3). Postoperative complications, recurrence‐free survival and overall survival were evaluated using multivariable Cox proportional hazards models. Paired pathologic reassessment was performed in patients undergoing repeat resection for recurrent HCC. Results Burnt‐out MASLD exhibited the most adverse oncologic phenotype. Relative to the reference phenotype (S > 1/F < 3), burnt‐out MASLD was not associated with increased perioperative morbidity but was independently associated with a higher recurrence risk (HR 1.87, 95% CI 1.10–3.17; p = 0.020) and markedly reduced overall survival (HR 3.38, 95% CI 1.57–7.28; p = 0.002). In contrast, steatosis loss without advanced fibrosis and advanced fibrosis with preserved steatosis were not independently associated with recurrence. Paired histologic analysis ( n = 39) demonstrated relative stability of steatosis after tumour development, whereas fibrosis progression was observed in a substantial subset. Conclusions Burnt‐out MASLD represents a distinct histologic phenotype prognostically relevant after curative resection for HCC. Recognition of this entity may refine postoperative risk stratification and inform surveillance strategies in MASLD‐related HCC.
Watanabe et al. (Fri,) studied this question.