Lower creatinine to cystatin C ratio is associated with an increased risk of MAFLD: A cross-sectional and prospective study of 368,634 UK Biobank participants

Background: & Aims: Metabolic associated fatty liver disease (MAFLD) affects about a quarter of the world's adults, and screening out the high-risk population with at an early stage is a challenge. As a sarcopenia index, the relationship between creatinine to cystatin C ratio (CCR) and MAFLD remains unclear. This cross-sectional, prospective study aimed to explore the relationship between CCR and MAFLD. Methods: : This study included 368,634 participants from the UK Biobank for cross-sectional and prospective analyses. MAFLD was diagnosed according to international expert consensus, and mild and severe liver fibrosis were defined by FIB-4. Univariate and multivariate logistic regression analyses were used to calculate odds ratios (ORs) to evaluate the association between CCR levels and MAFLD. Cox regression models were used to determine the association between CCR and MAFLD-related severe liver disease (SLD). Results: : We grouped the study participants according to CCR tertiles. In cross-sectional and prospective analyses, participants in CCR tertile 1 had the highest MAFLD risk (OR 1.075, 95%CI 1.058-1.093, P <0.001, and OR 1.340, 95%CI 1.077-1.669, P =0.009). In males, CCR was significantly associated with severe liver fibrosis (OR 1.657, 95%CI 1.476-1.859, P <0.001). Cox analyses showed that participants in CCR tertile 1 had the highest risk of MAFLD-related SLD (HR 4.23, 95%CI 3.54-4.05, P <0.001), and the SLD cumulative incidence during follow-up was obviously higher than others. Conclusion: Our results indicated that lower CCR was significantly associated with higher risk of MAFLD. Moreover, CCR can predict the risk of MAFLD-related SLD and severe liver fibrosis, which can potentially be used as a large-scale non-invasive tool to dynamically monitor the occurrence and development of MAFLD.