Screening for Hyperuricemia in Patients With Metabolic Associated Fatty Liver Disease (MAFLD)

Non-alcoholic fatty liver disease (NAFLD) has become increasingly prevalent in recent years and is now considered a leading cause of chronic liver disease worldwide, representing a major global public health challenge.

This growing prevalence is largely attributed to changes in lifestyle and dietary habits, making NAFLD the most common chronic liver condition globally, with an estimated global prevalence of 30.1%.

Recently, an international expert consensus proposed redefining NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD) to better reflect the disease's underlying metabolic basis. The diagnosis of MAFLD is based on the presence of hepatic steatosis in more than 5% of hepatocytes, in the absence of excessive alcohol intake or other causes of chronic liver disease. The diagnosis also requires at least one of the following three criteria: (1) overweight or obesity, (2) type 2 diabetes mellitus, or (3) evidence of metabolic dysregulation. Metabolic dysregulation is defined by the presence of at least two of the following abnormalities: increased waist circumference, elevated blood pressure, dyslipidemia, prediabetes, insulin resistance, or elevated plasma C-reactive protein (CRP) levels.

"Burned-out" NAFLD has been suggested as a potential hidden cause of cryptogenic cirrhosis. Therefore, early detection and management of NAFLD and its metabolic risk factors are critical to prevent disease progression and hepatic failure.

Uric acid (UA) is the final product of purine metabolism in the liver, with xanthine oxidase (XO) catalyzing the conversion of hypoxanthine to xanthine and subsequently to UA.

Abnormal UA metabolism is associated with various systemic diseases, including hypertension, atherosclerosis, diabetes mellitus, and dyslipidemia.

In recent years, increased interest has been directed toward the relationship between serum uric acid (SUA) levels and NAFLD severity. SUA has been identified as an independent risk factor significantly correlated with NAFLD severity, regardless of other metabolic markers. Studies have shown a 21% increase in NAFLD risk for every 1 mg/dL rise in SUA, and hyperuricemia is associated with a higher risk of advanced liver fibrosis in NAFLD patients.

Given the strong association between SUA levels and NAFLD progression, SUA-lowering therapy has emerged as a potential strategy for improving liver outcomes. Xanthine oxidase inhibitors, such as febuxostat and allopurinol, are commonly used to reduce SUA levels and have shown promise in improving liver histology in patients with NAFLD