Higher Platelet-to-Neutrophil Ratio Linked With Lower MASLD Odds

A higher platelet-to-neutrophil ratio (PNR) was independently associated with lower odds of metabolic dysfunction–associated steatotic liver disease (MASLD) and advanced liver fibrosis among US adults, according to a cross-sectional analysis recently published in the International Journal of Endocrinology.¹

Why Researchers Examined PNR in MASLD

The study authors noted that existing biomarkers used to identify MASLD and its progression have limited clinical utility, but evidence suggests that neutrophils and platelets both play a role in disease progression. Although PNR, a readily available marker derived from routine blood counts, has shown prognostic value in conditions such as ovarian cancer and aneurysm rupture, its relationship with MASLD has not been fully studied, they added.

Identifying patients at risk of fibrosis early has taken on added importance following FDA approval of resmetirom (Rezdiffra; Madrigal Pharmaceuticals) and semaglutide (Wegovy; Novo Nordisk) for metabolic dysfunction–associated steatohepatitis with moderate to advanced fibrosis.^2,3 At-risk patients may be candidates for treatment.

To evaluate PNR’s relationship with MASLD, the researchers analyzed data from the National Health and Nutrition Examination Survey dataset, spanning 2017 to March 2020.¹ They defined hepatic steatosis as a controlled attenuation parameter of at least 274 dB/m. MASLD required steatosis plus at least 1 cardiometabolic risk factor, and advanced fibrosis was defined as a liver stiffness measurement of at least 8.2 kPa.

How PNR Related to MASLD and Fibrosis Risk

The study included 3437 adults, with a weighted mean age of 47.5 (17.5) years. Among them, the weighted prevalence was 41.8% for hepatic steatosis, 41.7% for MASLD, and 8.3% for advanced fibrosis. Participants in higher PNR quartiles were younger, had lower body mass index (BMI), and had lower prevalences of diabetes, hypertension, dyslipidemia, steatosis, and advanced fibrosis, the researchers noted.

In the main adjusted model, each doubling of PNR was associated with 25% lower odds of MASLD (OR, 0.75; 95% CI, 0.63-0.90). Participants in the highest PNR quartile had 38% lower odds of MASLD than those in the lowest quartile (OR, 0.62; 95% CI, 0.48-0.81). However, in a sensitivity model that also adjusted for BMI, diabetes, hypertension, dyslipidemia, and alanine aminotransferase level, the association was attenuated and no longer statistically significant (OR, 1.17; 95% CI, 0.93-1.49). The authors treated this as a sensitivity analysis rather than the primary model because several of those factors contribute to the MASLD definition.

Higher PNR was also inversely associated with advanced fibrosis in the main model (OR, 0.43; 95% CI, 0.33-0.57). This association was reduced in the sensitivity model but remained statistically significant (OR, 0.68; 95% CI, 0.49-0.94).

The relationship between PNR and MASLD was nonlinear, with a breakpoint at a PNR of approximately 38. PNR values above that level, observed in about 90% of participants, were associated with significantly lower odds of MASLD (OR, 0.60; 95% CI, 0.51-0.70). For advanced fibrosis, the inverse association was consistent across the range of PNR values.

What Limits the Clinical Use of PNR

The authors acknowledged several limitations, including the cross-sectional design, which cannot establish causality. In addition, because PNR was measured at a single time point, acute infection, inflammation, or medications affecting blood counts may have influenced the results. The study also could not determine whether PNR provides additional predictive value beyond established markers.

Despite these limitations, the researchers concluded that their findings suggest PNR is “a readily available composite marker that is independently associated with MASLD.”

“…further prospective cohort studies are needed to validate these findings and to clarify the temporal relationship,” they wrote.

References

1. Zhang Y, Zhang H, Li S, et al. 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. Int J Endocrinol. 2026;2026:5591067. doi:10.1155/ije/5591067
2. Joszt L. FDA approves resmetirom, first treatment for NASH with liver fibrosis. AJMC^®. March 14, 2024. Accessed October 16, 2026. https://www.ajmc.com/view/fda-approves-resmetirom-first-treatment-for-nash-with-liver-fibrosis
3. Klein HE. FDA approves semaglutide for MASH with fibrosis. AJMC. August 18, 2025. Accessed October 16, 2026. https://www.ajmc.com/view/fda-approves-semaglutide-for-mash-with-fibrosis