Risk Factors of Hepatocellular Carcinoma for Precision Personalized Care

Chronic fibrotic liver disease caused by viral or metabolic etiologies is a high-risk condition for developing hepatocellular carcinoma (HCC). Even after complete HCC tumor resection or ablation, the carcinogenic tissue microenvironment in the remnant liver can give rise to recurrent HCC tumors, which progress into incurable, advanced-stage disease in most patients. Thus, early detection and prevention of HCC development will be the most impactful strategy to improve the dismal HCC prognosis. However, practice-guideline-recommended “one-size-fits-all” HCC screening (or interchangeably, “surveillance”) for early tumor detection is utilized in less than 20% of the target population, and performance of screening modalities is suboptimal. Furthermore, optimal screening strategies for emerging at-risk patient populations such as chronic hepatitis C after viral cure and noncirrhotic nonalcoholic fatty liver disease are yet to be established. Clinical and molecular HCC risk prediction will enable precise HCC risk estimation followed by tailored HCC screening for individual patients to maximize its cost-effectiveness and optimize allocation of limited resources for the screening. Biomarker development can be facilitated by utilizing unified framework (e.g., PRoBE design) and resources (e.g., Early Detection Research Network and Texas Hepatocellular Carcinoma Consortium biorepositories).