Non-HDL-to-HDL-cholesterol ratio and metabolic dysfunction-associated steatotic liver disease: a systematic review...

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and is linked to dyslipidemia and cardiometabolic dysfunction. The non-HDL cholesterol to HDL cholesterol ratio (NHHR) has emerged as a composite lipid biomarker that reflects the balance between atherogenic and anti-atherogenic lipoproteins and may have utility in MASLD risk stratification. However, the strength and consistency of the association between NHHR and MASLD remain uncertain. This systematic review and meta-analysis aimed to synthesize the available evidence regarding the association between NHHR and MASLD and evaluate its diagnostic performance.

A systematic search of PubMed, Embase, and Google Scholar was conducted from database inception through January 2026 in accordance with PRISMA guidelines. Original human studies evaluating the relationship between NHHR and MASLD were included. Random-effects meta-analyses were performed to calculate pooled standardized mean differences (SMDs) in NHHR between individuals with and without MASLD, pooled odds ratios (ORs) for MASLD according to NHHR levels, and pooled area under the receiver operating characteristic curve (AUC) to evaluate diagnostic performance. Study quality was assessed using the Newcastle-Ottawa Scale.

Twenty-four studies were included in the systematic review, and 19 studies comprising 120,985 participants were included in the quantitative synthesis. Individuals with MASLD had significantly higher NHHR values than controls (pooled SMD = 1.01, 95% CI: 0.17-1.84; p = 0.018). Higher NHHR levels were associated with increased odds of MASLD (pooled OR = 1.56, 95% CI: 1.25-1.96; p < 0.001). A clear dose-response relationship was observed, with progressively greater odds of MASLD across increasing NHHR categories: OR = 1.60 (95% CI: 1.21-2.13) for Q2/T2 versus Q1/T1, OR = 1.87 (95% CI: 1.67-2.09) for Q3 versus Q1, and OR = 2.19 (95% CI: 1.77-2.70) for Q4/T3 versus Q1/T1. Twelve studies evaluating diagnostic accuracy demonstrated a pooled AUC of 0.73 (95% CI: 0.70-0.75), indicating moderate discriminatory ability of NHHR for identifying MASLD.

NHHR is significantly associated with MASLD and demonstrates a graded relationship with disease association, whereby higher NHHR levels correspond to progressively greater odds of MASLD. Furthermore, NHHR exhibits moderate diagnostic accuracy for identifying MASLD. As a simple, inexpensive, and widely available metric derived from routine lipid testing, NHHR may serve as a practical adjunctive biomarker for MASLD risk stratification and may help identify individuals who could benefit from further evaluation.