Machine learning predicts hepatocellular carcinoma risk from routine clinical data: a large population-based multicentric study
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
Hepatocellular carcinoma (HCC) is a highly fatal tumor, for which risk stratification is crucial, yet remains challenging. Here, we develop an interpretable machine-learning framework for HCC risk stratification based on routinely collected clinical data. We utilize prospectively collected multimodal data from over 900,000 individuals and 983 cases of HCC across two population-scale cohorts: the "UK Biobank study" (development) and the "All of Us Research Program" (external testing). We assess individual and cumulative contributions of data modalities including demographics, lifestyle, health records, blood, genomics, and metabolomics. Our final, random-forest-based models significantly outperform all publicly available state-of-the-art risk-scores on both internal and external test sets. We demonstrate robustness across ethnic subgroups, provide comprehensive interpretability and release all code, model weights and a web-calculator for external validation and agentic integration. Our study presents PRE-Screen-HCC, a robust and interpretable machine-learning framework for HCC risk stratification and early detection.
Details
| Original language | English |
|---|---|
| Pages (from-to) | 1304–1322 |
| Journal | Cancer discovery |
| Volume | 16 |
| Issue number | 7 |
| Early online date | 26 Mar 2026 |
| Publication status | Published - 1 Jul 2026 |
| Peer-reviewed | Yes |
External IDs
| ORCID | /0000-0002-3730-5348/work/212492328 |
|---|---|
| ORCID | /0009-0000-2447-2959/work/212492469 |
| unpaywall | 10.1158/2159-8290.cd-25-1323 |
Keywords
Keywords
- Risk Assessment, Humans, Liver Neoplasms/epidemiology, Middle Aged, Risk Factors, Carcinoma, Hepatocellular/epidemiology, Female, Male, Predictive Learning Models, Aged, Machine Learning