Hepatocellular carcinoma (HCC) is highly preventable. Overall, 2/3 of HCC cases are attributable to five risk factors: chronic infection with hepatitis C virus (HCV), hepatitis B virus (HBV), excess alcohol associated liver disease (ALD), overweight/obesity associated liver diseases (metabolic dysfunction associated steatotic liver disease or MASLD), and tobacco smoking. HCV and HBV screening and treatment, ALD and MASLD screening with subsequent behavioral and pharmacological interventions hold the promise of reducing HCC incidence and mortality. Notably, the preventable burden differs by race/ethnicity and by sex. The risk factor profile for HCC is changing from less prevalent but highly potent factors (HBV and HCV) to highly prevalent but less potent factors (ALD and MASLD). This shift highlights the crucial role of HCC risk stratification among people with ALD and MASLD. . I present a framework that outlines steps and interfaces along the cancer care continuum that are required for effective HCC prevention. These steps include risk assessment, primary prevention, detection (i.e., screening initiation and follow-up of screening results), diagnosis, and treatment. Each of these steps is prone to failures that are influenced by factors at multiple socioecological levels (i.e., patient, provider, health delivery system, community, and policy levels). Focusing on early steps in the framework, including risk assessment, primary prevention, and early detection may have the greatest potential to reduce HCC mortality.
