A multinational research team including researchers at Severance Hospital has found that liver cancer risk in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) can be accurately predicted using a simple, non-invasive, two-step evaluation approach.

Severance Hospital collaborated with the Chinese University of Hong Kong and 16 institutions across the U.S., Europe, and Asia to validate the clinical utility of the method.

MASLD, previously known as non-alcoholic fatty liver disease (NAFLD), is characterized by fat accumulation in the liver in individuals who consume little or no alcohol. Closely linked to metabolic disorders such as diabetes, hypertension, and obesity, the disease affects roughly 30 percent of the global population.

In the study, the research team, participated by Professors Kim Seung-up and Lee Hye-won of the Department of Internal Medicine at Severance Hospital, assessed a two-step screening strategy recommended by the American Association for the Study of Liver Diseases (AASLD).

The first step involves calculating the fibrosis index (FIB-4) through a blood test.

Patients with elevated FIB-4 scores then undergo vibration-controlled transient elastography (VCTE), a non-invasive ultrasound technique that measures liver stiffness.

Tracking 12,950 MASLD patients over an average of 47 months, the team found that those with an FIB-4 score of 3.25 or higher or a liver stiffness measurement of 20 kPa or more had an annual liver cancer incidence exceeding one percent -- a threshold for initiating regular cancer surveillance. Patients with high FIB-4 scores and stiffness values above 15 kPa were also classified as high risk, regardless of cirrhosis status.

In contrast, patients with high FIB-4 but low liver stiffness had less than a 0.3 percent chance of developing liver cancer within three years, suggesting they could be safely excluded from routine surveillance.

The approach demonstrated strong predictive performance, with an area under the receiver operating characteristic curve (AUROC) of 0.733, a positive predictive value of 7.9 percent, a negative predictive value of 99.7 percent, and an overall accuracy exceeding 93 percent.

“This study presents a practical and simple clinical strategy for predicting disease progression in MASLD patients,” Professor Kim said. “Importantly, the two-step method can be applied regardless of cirrhosis status, helping to overcome limitations of current liver cancer surveillance guidelines.”

Professor Lee also said, “Given that MASLD patients can develop liver cancer even without cirrhosis, this validated strategy could contribute to establishing tailored surveillance systems.”

It ensures high-risk patients are not overlooked while sparing low-risk individuals from unnecessary testing, Lee added.

The findings were published in the latest issue of Gut.