The C-reactive protein-albumin-lymphocyte index: a novel biomarker for metabolic dysfunction-associated fatty liver disease across three ethnic cohorts

Background Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as a widespread chronic hepatic disorder worldwide. Early identification of individuals at elevated likelihood of MAFLD is crucial for preventing disease progression. The C-reactive protein-albumin-lymphocyte (CALLY) index, a novel composite biomarker reflecting systemic inflammation, nutritional status, and immune competence, offers potential utility in risk stratification. This study analyzed the relationship between the CALLY index and MAFLD prevalence utilizing cross-sectional data from three ethnically diverse cohorts in the U.S., the U.K and China. Methods This cross-sectional study employed data from the US NHANES (2017–2020), the UK Biobank, and a Chinese hospital cohort. MAFLD was diagnosed via ultrasound-based controlled attenuation parameter (CAP) or the fatty liver index (FLI). The CALLY index was calculated from serum albumin, lymphocyte count, and CRP, and was natural log-transformed (ln-CALLY). Its association with prevalent MAFLD was assessed using multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals, with restricted cubic splines (RCS) and subgroup analyses used to evaluate robustness and potential non-linearity. Results In NHANES, a per standard deviation (SD) increment in ln-CALLY was inversely associated with the odds of having MAFLD, corresponding to 24% lower odds (OR = 0.76, 95% CI: 0.64–0.90, p = 0.009). Similarly, in the UK Biobank cohort, each SD increase in ln-CALLY corresponded to 33% lower odds of MAFLD (OR = 0.67, 95% CI: 0.67–0.68, p < 0.001). A more pronounced risk reduction was observed in the Chinese population, where each SD rise in ln-CALLY was linked to 40% lower odds of MAFLD (OR = 0.60, 95% CI: 0.51–0.71, p < 0.001). The RCS analysis confirmed a non-linear inverse correlation between ln-CALLY and the odds of MAFLD, validating the dose-response protection identified through logistic regression. The area under the curve (AUC) of the ROC curve was 0.650 (95% CI: 0.636–0.665), indicating modest discriminative ability for identifying prevalent MAFLD. Conclusion The CALLY index demonstrates an inverse relationship with MAFLD prevalence. This biomarker may help identify individuals with a higher likelihood of MAFLD, which could inform screening and risk assessment in clinical and population settings.