Systemic immune-inflammatory biomarkers (SII, NLR, PLR and LMR) linked to non-alcoholic fatty liver disease risk

Front Immunol. 2024 Feb 28:15:1337241. doi: 10.3389/fimmu.2024.1337241. eCollection 2024.

Abstract

Background: Systemic immune-inflammatory biomarkers including systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have been demonstrated to be associated with the risk and severity of various liver diseases. However, studies on their role and clinical significance in metabolic diseases, especially in nonalcoholic fatty liver disease (NAFLD), are limited and results are inconsistent.

Methods: 10821 adults aged 20 years or older were enrolled in this cross-sectional study, sourced from six cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted logistic regression was employed to investigate the correlation between systemic immune-inflammatory biomarkers (SII, NLR, PLR, and LMR) and NAFLD risk. Restricted cubic spline regression models and segmented regression models were used to describe nonlinear relationships and threshold effects. Subgroup and sensitivity analyses were also conducted.

Results: After adjusting for all confounding variables, there was a significant positive association observed between ln-transformed SII (OR= 1.46, 95% CI: 1.27-1.69, P <0.001), NLR (OR= 1.25, 95% CI: 1.05-1.49, P =0.015), LMR (OR= 1.39, 95% CI: 1.14-1.69, P = 0.002) with NAFLD. A nonlinear dose-response relationship with an inverted "U"-shaped threshold of 4.64 was observed between ln(PLR) and NAFLD risk. When ln(PLR) was below 4.64, each unit increase in ln(PLR) was associated with a 0.55-fold increase in the risk of NAFLD (OR= 1.55, 95% CI: 1.05-2.31, P <0.05). Conversely, when ln(PLR) exceeded 4.64, each unit increase in ln(PLR) was associated with a 0.40-fold decrease in the risk of NAFLD (OR= 0.60, 95% CI. 0.44-0.81, P <0.05).

Conclusion: ln-transformed SII, NLR, and LMR were linearly associated with NAFLD risk. ln(PLR) showed an inverted "U"-shaped nonlinear dose-response relationship with the risk of NAFLD.

Keywords: NAFLD; NHANES; metabolic disease; population-based study; systemic immune-inflammatory biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cross-Sectional Studies
  • Humans
  • Inflammation
  • Lymphocytes
  • Monocytes
  • Neutrophils
  • Non-alcoholic Fatty Liver Disease* / diagnosis
  • Nutrition Surveys

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by The National Natural Science Foundation of China (82374291); 2022 “Tianfu Qingcheng Plan” Tianfu Science and Technology Leading Talents Project (Chuan Qingcheng No. 1090); the National TCM Clinical Excellent Talents Training Program (National TCM Renjiao Letter [2022] No. 1); “100 Talent Plan” Project of Hospital of Chengdu University of Traditional Chinese Medicine (Hospital office [2021] 42); Special subject of scientific research of Sichuan Administration of Traditional Chinese Medicine (2021MS539, 2023MS608, 2023MS071); Sichuan Science and Technology Program (2023ZYD0050, 24NSFJQ0077, MZGC20230056); Sichuan Philosophy and Social Science Planning Major Programs (SC22ZD010).