Serum Cytokeratin 18 Fragment Is an Indicator for Treating Metabolic Dysfunction-Associated Steatotic Liver Disease

Background and Aims: Although numerous noninvasive diagnostic methods have been developed to predict liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD), they lack markers for predicting lobular inflammation, hepatocellular ballooning, or changes related to metabolic dysfunction-associated steatohepatitis (MASH). We examined serum cytokeratin 18 fragment (CK18F) as a noninvasive marker for predicting treatment response and “at-risk MASH” and “MASH resolution” in patients with MASLD. Methods: One-hundred-and-ten patients with MASLD who underwent repeated biopsy were enrolled (age, 4 [0.5–21] years) in this retrospective study. We investigated associations among serum CK18F levels, liver histology, and blood tests and compared them with changes in serum CK18F levels and liver histology and the resolution of MASH. Additionally, 565 biopsy-proven patients were analyzed for associations among serum CK18F levels, liver histology, and blood tests. Moreover, the Fibrosis-4 (FIB-4) index and CK18F were examined for their usefulness in predicting ''at-risk MASH.'' Results: CK18F changes were strongly correlated with changes in lobular inflammation, hepatocellular ballooning, and nonalcoholic fatty liver disease activity score. Multiple regression analysis showed that contributing to “MASH resolution” was associated with changes in CK18F levels as independent factors. Patients diagnosed with MASLD and an FIB-4 index >2.67, or those with an FIB-4 index ≤2.67 and CK18F > 200 U/L, were at high risk of developing MASH and should be referred to a hepatologist. Conversely, those with an FIB-4 index ≤2.67 and CK18F ≤ 200 U/L were effectively managed through regular follow-up appointments. Conclusion: CK18F changes are associated with nonalcoholic fatty liver disease activity score changes and are a promising noninvasive diagnostic marker for ''at risk MASH'' and ''MASH resolution.''