Blood Test Marker Helps Identify Fatty Liver Patients at Risk for Cirrhosis
A new study reveals that measuring alkaline phosphatase alongside standard FIB-4 scores helps identify fatty liver patients at high risk of severe complications, improving early detection.
A new study reveals that measuring the alkaline phosphatase (ALK) enzyme in routine blood tests can significantly improve risk assessment for patients with fatty liver disease, particularly when standard scoring yields ambiguous intermediate results. Researchers found that combining ALK levels with the established FIB-4 scarring score helps identify individuals at elevated risk for severe liver complications over a ten-year period.
Understanding Fatty Liver and the FIB-4 Score
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the world's most common chronic liver condition, closely linked to obesity and type 2 diabetes. In its early stages, the accumulation of fat often goes unnoticed, but for some patients, it triggers inflammation and progressive tissue scarring known as fibrosis. To estimate this scarring risk, clinicians routinely rely on the FIB-4 score, which factors in patient age, platelet counts, and two liver enzymes, ALT and AST. While low scores generally indicate minimal risk, intermediate or high scores prompt specialized evaluations, most commonly a FibroScan ultrasound to measure liver stiffness.
Insights from the Beilinson Hospital Study
Published in the journal Digestive and Liver Disease, the large-scale study was initiated by Dr. Or Shemony and Dr. Emma Hajjaj from Department D of Internal Medicine at Beilinson Hospital, alongside Shiri Kushnir and Prof. Amir Shlomai. The research team examined the medical records of 388,933 health fund members aged 35 and older, followed between 2004 and 2025. Approximately 29 percent of participants had a diagnosis of fatty liver disease, while the remainder were included due to type 2 diabetes and a body mass index (BMI) exceeding 27.
During an average follow-up of 7.4 years, researchers tracked the first occurrence of severe liver complications, including cirrhosis, liver cancer, or advanced liver disease manifestations. The data demonstrated that across all FIB-4 risk groups, individuals with elevated ALK levels—defined as 120 units per liter or higher—faced a higher estimated rate of ten-year liver complications. Among participants with intermediate FIB-4 scores, those with high ALK levels exhibited a 2.8 percent complication rate compared to 1.6 percent for those with normal ALK. After adjusting for confounding variables such as age, diabetes, and renal function, the risk profile for intermediate FIB-4 patients with high ALK closely mirrored that of patients with high FIB-4 scores and normal ALK.
Clinical Recommendations and Future Steps
Because alkaline phosphatase originates from both the liver and bones, experts stress that an isolated high reading requires careful interpretation. Clinicians often check an additional enzyme, GGT, to determine if the elevation stems from the hepatic system or bile ducts, while also ruling out bone conditions, vitamin D deficiencies, or medication effects. Prof. Shlomai advises patients with intermediate FIB-4 scores and elevated ALK to undergo a FibroScan and a specialized hepatology evaluation.
"There is no reason for panic, but there is every reason for a proper medical investigation," Prof. Shlomai noted.
Researchers emphasize that while these findings highlight a valuable predictive tool, further prospective studies across broader populations are necessary before ALK can be formally integrated into official clinical guidelines. In the interim, health professionals recommend discussing unexpected ALK elevations with a primary care physician to determine the appropriate diagnostic pathway.
