Metabolic-associated fatty liver disease (MAFLD) 2024–2026: modern approaches to diagnosis and treatment — a practical guide for a clinician

Abstract

Metabolic-associated fatty liver disease (MAFLD) is a systemic metabolic disorder inextricably linked with obesity, type 2 diabetes mellitus and cardiovascular diseases. The pathology is associated with an increased risk of cardiovascular mortality, the development of extrahepatic malignancies, as well as the progression of fibrosis to cirrhosis and hepatocellular carcinoma. The diagnostic algorithm begins with calculating the FIB-4 index in all patients with type 2 diabetes, obesity, identified steatosis, or elevated transaminases. For FIB-4 values of 1.30–2.67, elastography or ELF test is indicated (in the Russian Federation analogues FibroMax, NES-Fibrotest). It is important that normal transaminase levels do not exclude steatohepatitis: up to 30–40% of patients with histologically verified steatohepatitis have normal ALT and AST. In turn, an increase in ALT/AST is not a hallmark for the diagnosis of steatohepatitis. Liver biopsy remains the “gold standard” but is not routine due to invasiveness and sampling error. Biopsy is indicated only when the results of non-invasive tests are inconclusive, as well as when there is a suspicion of concomitant pathology. The basis of treatment is weight loss of ≥7–10%, a Mediterranean diet and physical activity ≥150/min/week. Resmetirom and semaglutide are FDA-approved for the treatment of metabolic-associated steatohepatitis (MASH), but these drugs are not registered for this indication in the Russian Federation as of 2026. Semaglutide is registered in Russia for the treatment of diabetes and obesity, allowing for its off-label use in MASH. Along with it, liraglutide, SGLT2 inhibitors and pioglitazone in combination with SGLT2 inhibitors are used off-label. Monitoring after 6–12 months: decrease in liver stiffness ≥20%, decrease in ALT ≥20%, decrease in CAP ≥30 dB/m, decrease in FIB-4 ≥0.5, decrease in body weight ≥7–10% from baseline.