Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide and a major cause of death among patients with cirrhosis.¹ The growing burden of metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease has reshaped the epidemiology of chronic liver disease, including cirrhosis and HCC.¹ Although advances in surgical, locoregional, and systemic therapies have improved outcomes, many cases are still diagnosed late because of limitations and underutilization of current surveillance approaches, leading to poor outcomes.¹ This highlights the need for more precise HCC risk stratification and biomarker-based surveillance.¹ In response, the American Gastroenterological Association (AGA) developed a Clinical Practice Update to provide practical guidance on HCC risk stratification and surveillance, with emphasis on emerging biomarkers, risk prediction models, and strategies to improve early detection.¹

Commissioned by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board, the AGA Clinical Practice Update was developed by hepatology experts based on a review of the available evidence and expert interpretation of the literature.¹ The update presents eight Best Practice Advice statements on HCC prevention, surveillance eligibility, risk stratification, and emerging surveillance technologies.¹ The document underwent internal peer review by the Clinical Practice Updates Committee and external review through the standard review process before publication, providing practical guidance for clinicians managing patients at risk of HCC.¹

Prevention of cirrhosis remains the cornerstone of reducing HCC morbidity and mortality, while semiannual ultrasound combined with α-fetoprotein (AFP) continues to be the preferred surveillance strategy for patients at risk of HCC.¹ Surveillance should be targeted at individuals most likely to benefit, particularly patients with cirrhosis and selected patients with chronic hepatitis B virus (HBV) without cirrhosis, while balancing potential physical, psychological, and financial harms through individualized decision-making.¹

The update also highlights emerging strategies that may improve HCC surveillance, including blood-based biomarkers such as GALAD and GAAD, liquid biopsy technologies, circulating tumor-derived markers, and abbreviated magnetic resonance imaging (MRI) protocols.¹ Although these approaches have shown promising performance, more evidence is required to support their routine clinical use, and ultrasound + AFP remains the standard of care.¹ The update also emphasizes the importance of risk stratification, noting that most prediction models require further validation, while PAGE-B and REAL-B are currently the best-validated tools to guide surveillance decisions in patients with chronic HBV infection.¹

Collectively, these developments reflect a shift toward more risk-adapted and personalized HCC surveillance strategies, although further validation is required before integration into routine clinical practice.¹ The key Best Practice Advice statements from the AGA update are summarized in table 1.

No.	Summary of the Best Practice Advice statements
Prevention of HCC
1	Prevent HCC morbidity and mortality through vaccination, antiviral therapy (HBV and HCV), alcohol-use management, metabolic risk control, and early liver disease intervention
Standard surveillance
2	Semiannual ultrasound + AFP remains the preferred surveillance strategy for patients at risk of HCC, enabling earlier HCC detection, access to curative therapies, and improved survival. Populations recommended for HCC surveillance include: Child-Pugh class A or B cirrhosis, regardless of etiology, including: Hepatitis C (viremic and post SVR) Hepatitis B Alcohol-associated liver disease MASLD Other etiologies (e.g. primary biliary cholangitis and autoimmune liver disease) Child-Pugh class C cirrhosis, if transplant candidate Chronic hepatitis B without cirrhosis Men aged >40 years from endemic countries Women aged >50 years from endemic countries Patients from Africa at an earlier age Family history of HCC PAGE-B score ≥10
Surveillance in non-cirrhotic patients
3	In patients without cirrhotic, HCC surveillance is indicated only for a subset of those with chronic HBV infection and is not advised for other etiologies due to low annual incidence
Surveillance harms
4	Potential physical, psychological, and financial harms should be considered despite established benefits of HCC surveillance
Novel biomarkers
5	Novel blood-based (e.g. GALAD) and radiologic biomarkers are undergoing clinical validation, but evidence is insufficient to support their use in routine HCC surveillance and should not replace guideline-recommended tests at present
Multicancer detection panels
6	Multicancer blood-based biomarker detection panels should not be used in the screening or surveillance of patients at risk for HCC
Risk stratification in cirrhosis
7	Multiple HCC risk-stratification scores exist for patients with cirrhosis. However, few scores have undergone sufficient external validation to support routine clinical implementation
Risk stratification in chronic HBV infection
8	PAGE-B and REAL-B scores may be used to stratify future HCC risk among patients with chronic HBV infection Model Components Risk groups and cutoffs PAGE-B Age, sex, platelet count Low risk: <10 Intermediate risk: 10-17 High risk: ≥18 REAL-B Age, male, alcohol use, cirrhosis, diabetes, platelet, AFP Low risk: <4 Intermediate risk: 4-7 High risk: 8-13

 

Table 1. Summary of the AGA Clinical Practice Update Best Practice Advice statements HCC prevention, surveillance, and risk stratification

AFP: α-fetoprotein; AGA: American Gastroenterological Association; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; MASLD: metabolic dysfunction-associated steatotic liver disease; SVR: sustained virologic response.

 

In an interview with Omnihealth Practice, Prof. Chan Wah Kheong, Consultant Hepatologist and Gastroenterologist from Malaysia, discussed the evolving landscape of hepatocellular carcinoma (HCC), the importance of early surveillance, and the need for collaborative efforts to improve patient outcomes.

 

Q1. How has the landscape of HCC changed in Malaysia, and where do you see the greatest opportunity to reduce its burden?

Prof. Chan: The epidemiology of HCC in Malaysia has changed considerably over the past decade, with metabolic dysfunction-associated steatotic liver disease (MASLD) overtaking chronic hepatitis B as the leading cause of HCC. This shift reflects rising obesity, diabetes, and other cardiometabolic risk factors, underscoring the need for earlier identification and management of chronic liver disease.

Our greatest opportunity to reduce the HCC burden lies in prevention. Clinicians play a pivotal role in promoting healthy lifestyle modifications, optimizing metabolic risk factors, and ensuring appropriate antiviral treatment for chronic hepatitis B and C to prevent progression to cirrhosis. Early identification of advanced liver fibrosis is also essential to enable appropriate monitoring and intervention. By addressing underlying liver disease and identifying advanced fibrosis early, we can reduce progression to cirrhosis and ultimately the risk of HCC.

Q2. How can clinicians optimize HCC surveillance in patients at risk, and what challenges remain in the Malaysian healthcare landscape?

Prof. Chan: Early detection begins with identifying patients with advanced liver fibrosis before HCC develops. Malaysia was among the first countries to incorporate liver assessment into its type 2 diabetes clinical practice guideline using a two-step risk stratification pathway. Patients are initially assessed using the FIB-4 score, followed by liver stiffness measurement for those with elevated scores to enable timely specialist referral and HCC surveillance. Automated FIB-4 reporting by hospitals and private laboratories has further simplified routine implementation. For high-risk patients, semiannual ultrasound and AFP remain the mainstay of HCC surveillance. However, disparities in healthcare access, limited availability of trained personnel and liver stiffness measurement, and logistical barriers continue to limit surveillance uptake.

Q3. How can a multidisciplinary team approach improve HCC prevention and surveillance in Malaysia?

Prof. Chan: Given the growing burden of MASLD, effective HCC prevention cannot be achieved by hepatologists alone. The Malaysian consensus is developed with input from hepatologists, endocrinologists, family medicine specialists, and radiologists to establish a coordinated approach to risk identification and timely referral. Within this collaborative care model, primary care physicians and endocrinologists play a central role in identifying at-risk individuals, initiating fibrosis risk stratification, and managing lifestyle and cardiometabolic risk factors. Patients with advanced fibrosis can then be referred for specialist assessment and HCC surveillance, ensuring timely access to care while optimizing healthcare resources. Ultimately, HCC prevention requires a coordinated effort across healthcare professionals and society.