Faculty, Staff and Student Publications

Publication Date

8-1-2024

Journal

JHEP Reports

Abstract

BACKGROUND & AIMS: The effectiveness of surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is limited, due to inadequate risk stratification and suboptimal performance of current screening modalities.

METHODS: We developed a multicenter prospective cohort of patients with cirrhosis undergoing surveillance with MRI and applied global untargeted metabolomics to 612 longitudinal serum samples from 203 patients. Among them, 37 developed HCC during follow-up.

RESULTS: We identified 150 metabolites with significant abundance changes in samples collected prior to HCC (Cases) compared to samples from patients who did not develop HCC (Controls). Tauro-conjugated bile acids and gamma-glutamyl amino acids were increased, while acyl-cholines and deoxycholate derivatives were decreased. Seven amino acids including serine and alanine had strong associations with HCC risk, while strong protective effects were observed for N-acetylglycine and glycerophosphorylcholine. Machine learning using the 150 metabolites, age, gender, and

CONCLUSIONS: This study identified N-acetylglycine, amino acids, bile acids and choline-derived metabolites as biomarkers of HCC risk, and microbiota-derived metabolites as contributors to HCC development.

IMPACT AND IMPLICATIONS: The effectiveness of surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is limited. There is an urgent need for improvement in risk stratification and new screening modalities, particularly blood biomarkers. Longitudinal collection of paired blood samples and MRI images from patients with cirrhosis is particularly valuable in assessing how early blood and imaging markers become positive during the period when lesions are observed to obtain a diagnosis of HCC. We generated a multicenter prospective cohort of patients with cirrhosis under surveillance with contrast MRI, applied untargeted metabolomics on 612 serum samples from 203 patients and identified metabolites associated with risk of HCC development. Such biomarkers may significantly improve early-stage HCC detection for patients with cirrhosis undergoing HCC surveillance, a critical step to increasing curative treatment opportunities and reducing mortality.

Keywords

Hepatocellular carcinoma, Cirrhosis, Surveillance, Biomarkers, Metabolomics

DOI

10.1016/j.jhepr.2024.101119

PMID

39139459

PMCID

PMC11321296

PubMedCentral® Posted Date

5-15-2024

PubMedCentral® Full Text Version

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Graphical Abstract

Published Open-Access

yes

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