Circulating leptin in patients with nonalcoholic fatty liver disease-related liver fibrosis: a systematic review and a meta-analysis

J Gastroenterol Hepatol. 2024 May;39(5):806-817. doi: 10.1111/jgh.16480. Epub 2024 Jan 18.


Background and aim: Clinical data on the association between leptin levels and nonalcoholic fatty liver disease (NAFLD)-related liver fibrosis are conflicting. This meta-analysis aimed to compare circulating leptin between NAFLD patients with versus without liver fibrosis or non-NAFLD controls.

Methods: A systematic search was conducted in PubMed, Scopus, and the Cochrane Library. Fifteen studies were included, reporting data from 964 individuals (422 NAFLD patients with fibrosis, 297 NAFLD patients without fibrosis, 245 no-NAFLD controls).

Results: Leptin standardized mean difference (SMD) was higher in NAFLD patients with fibrosis (F1-F4) than in controls (SMD: 2.27; 95% confidence interval [CI]: 0.81-3.73); however, this association did not remain robust after the exclusion of studies with morbidly obese individuals. No difference was observed in leptin SMD between NAFLD patients with fibrosis and those without fibrosis (F0), and NAFLD patients without fibrosis versus controls. Heterogeneity was high (I2: 66-98%) among studies. Meta-regression analysis revealed a positive association of leptin SMD with homeostasis model assessment-insulin resistance, when comparing NAFLD patients with fibrosis versus NAFLD patients without fibrosis (beta: 0.53; 95% CI: 0.04-1.03), and a negative association of leptin SMD with age, when comparing NAFLD patients with fibrosis versus controls (beta: -0.29; 95% CI: -0.53 to -0.05).

Conclusion: Circulating leptin was higher in NAFLD patients with liver fibrosis than non-NAFLD controls, an association, however, attenuated after the exclusion of a study with morbidly obese individuals. Circulating leptin was not different between NAFLD patients with and without fibrosis, or NAFLD patients without fibrosis and controls.

Keywords: Adipokines; leptin; liver fibrosis; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis.

Publication types

  • Systematic Review
  • Meta-Analysis

MeSH terms

  • Biomarkers / blood
  • Female
  • Humans
  • Insulin Resistance
  • Leptin* / blood
  • Liver Cirrhosis* / blood
  • Liver Cirrhosis* / etiology
  • Male
  • Non-alcoholic Fatty Liver Disease* / blood
  • Non-alcoholic Fatty Liver Disease* / complications


  • Leptin
  • Biomarkers