Liver parenchymal quality stratifies outcomes after hepatic resection for hepatocellular carcinoma

Hepatic resection (HR) and liver transplantation (LT) are curative-intent treatments for hepatocellular carcinoma (HCC). Patients without cirrhosis are typically analyzed as a single group, obscuring potentially important differences between those with histologically normal liver and those with non-cirrhotic parenchymal disease. We aimed to characterize long-term outcomes following HR stratified by underlying parenchymal quality, with a contemporary LT cohort as an external benchmark. Retrospective cohort study of 662 adults undergoing curative-intent surgery for HCC at 2 tertiary centers (2010-2024). Resection patients (n=380) were stratified by non-tumor parenchymal histology into HR-Normal (n=84), HR-Diseased non-cirrhotic (n=159), and HR-Cirrhotic (n=137). A total of 282 LT recipients served as an external reference but were not entered into comparative models. Overall survival (OS) was analyzed by Kaplan-Meier and multivariable Cox regression, and recurrence by Fine-Gray competing-risks regression. Ninety-day mortality was low across resection strata (1.2%-3.2%). OS differed significantly across parenchymal groups (log-rank p =0.01), driven by superior outcomes in HR-Normal patients compared with both HR-Cirrhotic ( p =0.008) and HR-Diseased ( p =0.005). HR-Cirrhotic and HR-Diseased did not differ ( p =0.97). Five-year OS was 74.4%, 59.8% and 57.2%, respectively. On multivariable Cox regression, both cirrhosis (HR 2.03, 95% CI 1.16-3.54, p =0.01) and diseased non-cirrhotic parenchyma (HR 2.04, 95% CI 1.21-3.43, p =0.008) independently predicted death versus normal liver. Fine-Gray analysis confirmed higher recurrence risk in cirrhotic (sHR 2.09, p =0.01) and diseased non-cirrhotic (sHR 1.80, p =0.04) groups. The LT benchmark cohort achieved a 5-year OS of 82.4%. Histologically normal liver identifies a distinct HR subgroup with favorable oncologic outcomes. The conventional cirrhotic/non-cirrhotic dichotomy underestimates the prognostic impact of underlying parenchymal disease.