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Background <p>Non-alcoholic fatty liver disease (NAFLD) is a global public health crisis linked to elevated all-cause and cardiovascular mortality. The neutrophil-to-high-density lipoprotein ratio (NHR) is an emerging inflammatory-lipid biomarker that integrates systemic inflammation and lipid dysregulation. However, its prognostic value for long-term mortality in NAFLD remains undetermined.</p> Methods <p>We conducted a population-based prospective cohort study using data from the National Health and Nutrition Examination Survey (NHANES) 1999–2018. A total of 5,320 participants diagnosed with NAFLD were enrolled and divided into four groups according to quartiles of NHR (Q1-Q4). Multivariate Cox regression, restricted cubic spline, threshold effect, and subgroup analyses were used to evaluate the association between NHR and all-cause mortality.</p> Results <p>During a mean follow-up of 9.2 years, 1,172 all-cause deaths and 392 cardiovascular disease (CVD) deaths were documented. In the fully adjusted Cox models, higher NHR was significantly associated with elevated risks of all-cause mortality (HR = 1.27, 95% CI: 1.02–1.57) and CVD mortality (HR = 2.15, 95% CI: 1.44–3.22) in a dose-response manner, but not with cancer mortality. Further adjustment for blood lipids and hepatic function markers did not materially alter the results, supporting the robustness of the observed associations. Threshold and spline analyses further revealed a significant nonlinear relationship between NHR and all-cause mortality, with an inflection point of 2.072, when NHR was equal to or above 2.072, each 1-unit increase was associated with an 8% elevation in all-cause mortality risk (HR = 1.08, 95% CI: 1.04–1.12, <i>P</i> &lt; 0.001). Subgroup stratified analyses were performed as exploratory analyses. Although the association between elevated NHR and all-cause mortality reached statistical significance within several individual subgroups, no significant multiplicative interaction was detected for any stratifying factor, indicating no meaningful effect modification across these population strata.</p> Conclusion <p>Elevated NHR is independently associated with an increased risk of all-cause and cardiovascular mortality in NAFLD patients. NHR may serve as a simple, inexpensive, and readily available prognostic biomarker for risk stratification and clinical management in this population.</p>

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Association of neutrophil-to-high-density lipoprotein ratio with all-cause mortality among individuals with non-alcoholic fatty liver disease: the NHANES database prospective cohort study

  • 期刊论文

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  • 发表日期：

    2026年7月21日

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  • Yawei Xing,
  • Jie Wang,
  • Hebo Cheng,
  • Mengwei Xiao,
  • Fan Du,
  • Mengjun Qiu

摘要

Background

Non-alcoholic fatty liver disease (NAFLD) is a global public health crisis linked to elevated all-cause and cardiovascular mortality. The neutrophil-to-high-density lipoprotein ratio (NHR) is an emerging inflammatory-lipid biomarker that integrates systemic inflammation and lipid dysregulation. However, its prognostic value for long-term mortality in NAFLD remains undetermined.

Methods

We conducted a population-based prospective cohort study using data from the National Health and Nutrition Examination Survey (NHANES) 1999–2018. A total of 5,320 participants diagnosed with NAFLD were enrolled and divided into four groups according to quartiles of NHR (Q1-Q4). Multivariate Cox regression, restricted cubic spline, threshold effect, and subgroup analyses were used to evaluate the association between NHR and all-cause mortality.

Results

During a mean follow-up of 9.2 years, 1,172 all-cause deaths and 392 cardiovascular disease (CVD) deaths were documented. In the fully adjusted Cox models, higher NHR was significantly associated with elevated risks of all-cause mortality (HR = 1.27, 95% CI: 1.02–1.57) and CVD mortality (HR = 2.15, 95% CI: 1.44–3.22) in a dose-response manner, but not with cancer mortality. Further adjustment for blood lipids and hepatic function markers did not materially alter the results, supporting the robustness of the observed associations. Threshold and spline analyses further revealed a significant nonlinear relationship between NHR and all-cause mortality, with an inflection point of 2.072, when NHR was equal to or above 2.072, each 1-unit increase was associated with an 8% elevation in all-cause mortality risk (HR = 1.08, 95% CI: 1.04–1.12, P < 0.001). Subgroup stratified analyses were performed as exploratory analyses. Although the association between elevated NHR and all-cause mortality reached statistical significance within several individual subgroups, no significant multiplicative interaction was detected for any stratifying factor, indicating no meaningful effect modification across these population strata.

Conclusion

Elevated NHR is independently associated with an increased risk of all-cause and cardiovascular mortality in NAFLD patients. NHR may serve as a simple, inexpensive, and readily available prognostic biomarker for risk stratification and clinical management in this population.