AGA Clinical Practice Update on Risk Stratification and Emerging Surveillance Strategies for Hepatocellular...

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in patients with cirrhosis. Although advancements in surgical, locoregional, and systemic therapies have improved outcomes for patients with early-stage HCC, most cases are diagnosed at later stages due to both the limitations of currently recommended surveillance modalities and their underuse, with fewer than 1 in 4 patients with cirrhosis receiving surveillance for this tumor. Current guidelines recommend semiannual surveillance with ultrasound and α-fetoprotein, but this strategy has suboptimal sensitivity, and alternative imaging techniques (eg, computed tomography and magnetic resonance imaging) have their own risks and challenges with implementation. HCC surveillance has established benefits in certain at-risk populations, including patients with cirrhosis (of any etiology) and selected patients with chronic hepatitis B virus. The burden of HCC is rising most rapidly among patients with nonviral liver diseases, including metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease, among whom the annual incidence rate of HCC is significantly lower than was previously observed in patients with viral hepatitis. This underscores the need for better biomarker and risk-stratification tools to detect HCC earlier and improve surveillance efficiency, although integrating them into routine clinical practice presents a significant challenge. This American Gastroenterological Association (AGA) Clinical Practice Update aims to provide Best Practice Advice on emerging strategies for HCC risk stratification and surveillance.

This Expert Review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on this topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external review procedures through the standard review process for Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because a systematic review was not performed, these Best Practice Advice statements do not carry formal ratings of the quality of available evidence or the strength of the presented advice. Best Practice Advice Statements BEST PRACTICE ADVICE 1: The best strategy for reducing hepatocellular carcinoma morbidity and mortality is to prevent cirrhosis. These strategies include vaccination and treatment of viral hepatitis (eg, hepatitis C virus and hepatitis B virus), recognizing and treating alcohol use disorder, managing metabolic syndrome, and addressing liver diseases at early stages. BEST PRACTICE ADVICE 2: The preferred current surveillance strategy for patients at risk of hepatocellular carcinoma is semiannual ultrasound and α-fetoprotein in combination. The benefits of surveillance include a higher likelihood of detecting early-stage hepatocellular carcinoma, access to curative therapy, and improved survival. BEST PRACTICE ADVICE 3: Among patients without cirrhosis, only a subset of those with chronic hepatitis B virus should undergo hepatocellular carcinoma surveillance; surveillance is not advised for those without cirrhosis from other etiologies due to the low annual incidence rate. BEST PRACTICE ADVICE 4: Although the benefits of hepatocellular carcinoma surveillance are well established, it is important for clinicians to consider the potential physical, psychological, and financial harms associated with the process. BEST PRACTICE ADVICE 5: Several novel blood-based biomarkers, such as GALAD, and radiologic biomarkers are undergoing clinical validation. Some are already commercially available, but evidence is insufficient to support their use in routine hepatocellular carcinoma surveillance. These assays should not replace guideline-recommended tests, although their accessibility and potential cost-effectiveness may support broader use once sufficiently validated. BEST PRACTICE ADVICE 6: Multicancer blood-based biomarker detection panels should not be used in the screening or surveillance of patients at risk for hepatocellular carcinoma. BEST PRACTICE ADVICE 7: Many hepatocellular carcinoma risk-stratification scores exist for patients with cirrhosis. However, few scores have undergone sufficient validation to support their use in clinical practice. BEST PRACTICE ADVICE 8: Among patients with chronic hepatitis B virus infection without cirrhosis, PAGE-B and REAL-B scores can stratify patients based on their future risk of hepatocellular carcinoma.