Association of the Platelet-to-Neutrophil Ratio With Metabolic Dysfunction-Associated Steatotic Liver Disease and Liver Fibrosis in U.S. Adults: NHANES 2017-March 2020.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease that is not related to alcohol and is characterized by excessive accumulation of fat within liver cells. As one of the most common chronic liver diseases worldwide, MASLD affects about a quarter of the world's population and is expected to become a leading indication for liver transplantation by 2030. The disease not only increases the risk of cirrhosis and hepatocellular carcinoma, but also is closely associated with a variety of extra-hepatic complications such as type 2 diabetes and cardiovascular disease. Although many biomarkers such as N-terminal type III collagen propeptide (PRO-C3), enhanced liver fibrosis (ELF), and Fibrosis-4 Score (FIB-4) have been used to identify and predict MASLD and metabolic dysfunction-associated steatohepatitis (MASH), their clinical utility remains limited. Recent studies have shown that neutrophils and platelets play a crucial role in the progression of MASLD. The platelet-to-neutrophil ratio (PNR), a novel biomarker, has shown predictive value in ovarian cancer and myocardial infarction. However, PNR has not been fully studied in MASLD. The aim of this study was to investigate the association between PNR and MASLD and to explore its relationship with hepatic steatosis and fibrosis. Methods: This cross-sectional study included participants from the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020 pre-pandemic dataset. Hepatic steatosis was defined as a controlled attenuation parameter (CAP) ≥ 274 dB/m, and MASLD was defined as hepatic steatosis plus at least one cardiometabolic criterion according to the 2023 multisociety steatotic liver disease (SLD) nomenclature. Advanced liver fibrosis was defined as a liver stiffness measurement (LSM) ≥ 8.2 kPa. PNR was calculated as the platelet count divided by the neutrophil count and log2-transformed (log2-PNR). Missing covariates were handled by multiple imputation ( Results: A total of 3437 adults aged 18 years and older were included (mean age 47.5 ± 17.5 years; 48.1% male). In the fully adjusted model, higher log2-PNR was inversely associated with MASLD (OR 0.75 per doubling of PNR, 95% CI 0.63-0.90), and with hepatic steatosis; participants in the highest PNR quartile had lower odds of MASLD than those in the lowest quartile. Threshold effect analysis identified a breakpoint at PNR approximately 38 for MASLD, with a significant nonlinear pattern. Higher log2-PNR was also inversely associated with advanced fibrosis (OR 0.43, 95% CI 0.33-0.57), with no significant nonlinearity. Subgroup analyses showed that the inverse association was more pronounced in males and non-Hispanic White participants for MASLD (P for interaction = 0.009 and 0.037, respectively). Conclusion: Higher log2-PNR was inversely associated with the cross-sectional presence of MASLD and hepatic steatosis, and with advanced liver fibrosis, in U.S. adults. Log2-PNR, an easily obtained inflammatory marker, is independently associated with MASLD. These findings require validation in prospective cohort studies.