Concept, Diagnosis, and Treatment in Steatotic Liver Disease (SLD)

Abstract

 Steatotic liver disease (SLD) encompasses metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), drug-induced liver injury, and metabolic dysfunction-associated alcohol-related liver disease (MetALD), which represents an intermediate condition between MASLD and ALD. Significant progress has been made in the development of non-invasive diagnostic methods. In 2024, serum CK-18F was approved for insurance coverage in Japan as an adjunctive diagnostic tool for metabolic dysfunction-associated steatohepatitis (MASH). The CLIONE study demonstrated that the degree of liver fibrosis is a critical factor in predicting the occurrence of liver disease-related events. For non-invasive assessment of liver fibrosis, the FIB-4 index is recommended as a first-step screening tool. For second-step evaluations, imaging techniques such as ultrasound elastography or magnetic resonance elastography, as well as fibrosis biomarkers, are considered useful. Among fibrosis biomarkers, type IV collagen 7S and Mac-2 binding protein glycosylation isomer have proven utility. Additionally, the globally standardized ELF (enhanced liver fibrosis) test received insurance coverage in 2024. The Nara Declaration 2023 was issued with the aim of early detection of chronic liver diseases, but it has not been approved by all stakeholder. Regarding pharmacological therapy, the U.S. Food and Drug Administration (FDA) approved the thyroid hormone receptor-beta agonist resmetirom; however, it has not yet been approved in Japan. The GLP-1 receptor agonist semaglutide demonstrated significant improvements in MASH or liver fibrosis compared to placebo in the Phase 3 ESSENCE trial, raising expectations for its approval in Japan. Other promising antidiabetic agents include SGLT2 inhibitors and the dual GLP-1/GIP receptor agonist tirzepatide. In cases of hypertriglyceridemia with MASLD, pemafibrate is recommended based on findings from the PORTRAIT trial, which showed its superiority over DHA/EPA in patients with elevated triglycerides.