Hepatocellular Carcinoma Screening: From Current Standard of Care to Future Directions

Hepatocellular carcinoma (HCC) represents a significant portion of global cancer incidence and mortality. Screening with ultrasound with or without alpha-fetoprotein is recommended for those at high-risk. Although screening can lead to earlier treatment and better outcomes, existing screening paradigms have several flaws. Ultrasound does not capture all early lesions and has lower efficacy in specific populations such as patients with obesity or those with metabolic dysfunction-associated steatotic liver disease (MASLD). Additionally, individuals with noncirrhotic MASLD and chronic hepatitis C also develop HCC, although not at high enough rates to justify screening based on current standards. These individuals, however, represent a substantial proportion of new HCC cases given rising MASLD rates and the endemic nature of hepatitis C in certain regions. Risk-stratifying these populations may reveal subsets that are higher risk and warrant screening. Several imaging advances, including contrast-enhanced ultrasound and abbreviated MRI protocols, may improve detection compared with the current approach. Evaluation of risk stratification and validation of these new imaging methods via clinical trials would likely lead to adjusting screening guidelines. This narrative review provides a diagnostic and interventional radiology-focused summary of the HCC screening guidelines and their recent evolution and highlights emerging imaging methods as potential screening tools of the future.