Weighing HCC Surveillance for Patients With MASLD and F3 Fibrosis

In an interview with CancerNetwork® at The Liver Meeting® 2026, Hashem B. El-Serag, MD, MPH, vice president of the Learning Health System and chair and professor of the Department of Medicine at Baylor College of Medicine in Houston, Texas, discussed how clinicians should approach hepatocellular carcinoma (HCC) surveillance in patients with metabolic dysfunction–associated steatotic liver disease (MASLD) and advanced (F3) fibrosis.

Approximately one-fourth to one-third of MASLD-related HCC occurs in the absence of cirrhosis, yet current American Association for the Study of Liver Diseases (AASLD) guidance recommends against routine surveillance in patients with advanced fibrosis but no cirrhosis.¹ El-Serag, who presented on hepatic and extrahepatic cancer risk in MASLD at the meeting, noted that surveilling every patient with MASLD who does not have cirrhosis is not feasible.² In his view, patients with F3 fibrosis who have additional metabolic risk factors and a good life expectancy may merit surveillance, and emerging genetic testing and risk calculators may help identify those at highest risk.

Transcript:

CancerNetwork: Up to 30% of MASLD-related HCC may arise without recognized cirrhosis. How should teams approach patients with F3 fibrosis, and which markers could help decide who needs surveillance?

El-Serag: This is an important and difficult question, because a third of all MASLD-related liver cancers do not arise in the typical high-risk group we focus on for surveillance, which is patients with cirrhosis. The converse of that argument is that patients with MASLD and no cirrhosis number in the hundreds of millions globally, so it is impossible, inefficient, and ineffective to perform surveillance on all of them. F3 is the subgroup of patients without cirrhosis that has acquired the most attention, because their risk of liver cancer, while not elevated to the degree seen in cirrhosis, is higher than the rest.

In my opinion, which is not currently based on solid data, F3 coupled with additional risk factors for MASLD and a good life expectancy may merit surveillance. These additional risk factors are metabolic. If someone with F3 has diabetes, overweight or obesity, high blood pressure, and dyslipidemia, that would move me toward surveillance.

There are tools being studied that may soon become part of routine practice, like genetic testing panels. A patient who has the high-risk variants of PNPLA3 might sway me toward surveillance. We are also eagerly awaiting risk calculators that many groups are developing, which put in numbers what I just said in words: combining age, genetics, metabolic risk factors, and alcohol in 1 equation for patients with F3, dividing them into higher- and lower-risk groups, and focusing on the higher-risk group.

In summary, this is still a difficult area. It is reasonable to perform surveillance, particularly in the presence of additional risk factors, with an individualized discussion with the patient and their family about the benefits and risks.

References

1. Singal AG, Llovet JM, Yarchoan M, et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023;78(6):1922-1965. doi:10.1097/HEP.0000000000000466
2. El-Serag HB. MASLD and cancer risk—hepatic and extrahepatic malignancies: what clinicians need to know. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.