Molecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease.

ABSTRACT: Prediction of hepatocellular carcinoma (HCC) risk is an urgent unmet need in patients with nonalcoholic fatty liver disease (NAFLD). In cohorts of 409 patients with NAFLD from multiple global regions, we defined and validated hepatic transcriptome and serum secretome signatures predictive of long-term HCC risk in patients with NAFLD. A 133-gene signature, prognostic liver signature (PLS)-NAFLD, predicted incident HCC over up to 15 years of longitudinal observation. High-risk PLS-NAFLD was associated with IDO1⁺ dendritic cells and dysfunctional CD8⁺ T cells in fibrotic portal tracts along with impaired metabolic regulators. PLS-NAFLD was validated in independent cohorts of patients with NAFLD who were HCC naïve (HCC incidence rates at 15 years were 22.7 and 0% in high-

SUBMITTER: Fujiwara N 

PROVIDER: S-EPMC9236162 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature