From the Liver to Heart in Nonalcoholic Fatty Liver Disease: Single-Cell and Serum Evidence for Cytokeratin 18 in Predicting Cardiovascular Risk.

BACKGROUND

This study is aimed at measuring the expression of serum cytokeratin 18 (CK18) in patients with nonalcoholic fatty liver disease (NAFLD) and at evaluating its ability to discriminate NAFLD patients with and without coronary heart disease (CHD), thereby elucidating its potential role in reflecting the link between NAFLD and increased cardiovascular involvement.

METHODS

A total of 127 patients diagnosed with NAFLD and treated between September 2022 and July 2024 were enrolled in this cross-sectional study. Based on the presence or absence of CHD, they were divided into two subgroups: a CHD-present group (n = 79) and a CHD-absent group (n = 48). In addition, a control group consisting of 100 age-matched and sex-matched healthy individuals undergoing routine physical examinations during the same period was included for comparison.

RESULTS

Compared with the control group, patients with NAFLD showed significantly higher levels of alanine aminotransferase (ALT), serum CK18-M65 and CK18-M30 levels, body mass index (BMI), homeostasis model assessment of insulin resistance index (HOMA-IR), triglyceride (TG), total cholesterol (TC), aspartate aminotransferase (AST), and waist-to-hip ratio (p < 0.05). Multivariate logistic regression analysis identified serum CK18-M65, CK18-M30, TC, ALT, AST, and HOMA-IR as independent factors in NAFLD patients (p < 0.05). The combination of CK18-M65 and CK18-M30 yielded an area under the curve of 0.843, with a sensitivity of 87.34% and a specificity of 75.00%. Functional enrichment analysis revealed that CK18-related genes were involved in inflammatory signaling and cardiovascular regulatory pathways, supporting a mechanistic role for CK18 in the liver-heart axis.

CONCLUSION

Serum CK18 may serve as a useful biomarker for identifying NAFLD patients with concurrent CHD, offering diagnostic value in clinical assessment.