title: Circulating leptin in non-alcoholic fatty liver disease: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Clinical data regarding circulating leptin levels in patients with non-alcoholic fatty liver disease (NAFLD) are conflicting. The purpose of this meta-analysis was to compare leptin levels between the following groups: patients with biopsy-proven NAFLD vs controls; simple steatosis (SS) patients vs controls; non-alcoholic steatohepatitis (NASH) patients vs controls and NASH patients vs SS patients.
  
  
  METHODS
  We performed a systematic search in PubMed, Scopus and the Cochrane Library. We analysed 33 studies, published between 1999 and 2014, including 2,612 individuals (775 controls and 1,837 NAFLD patients).
  
  
  RESULTS
  Higher circulating leptin levels were observed in NAFLD patients vs controls (standardised mean difference [SMD] 0.640; 95% CI 0.422, 0.858), SS patients vs controls (SMD 0.358; 95% CI 0.043, 0.673), NASH patients vs controls (SMD 0.617; 95% CI 0.403, 0.832) and NASH patients vs SS patients (SMD 0.209; 95% CI 0.023, 0.395). These results remained essentially unchanged after excluding studies involving paediatric or adolescent populations and/or individuals undergoing bariatric surgery. There was moderate-to-severe heterogeneity among studies in all comparisons, but no significant publication bias was detected. Meta-regression analysis demonstrated that BMI was inversely associated with leptin SMD and accounted for 26.5% (p = 0.014) and 32.7% (p = 0.021) of the between-study variance in the comparison between NASH patients and controls and NAFLD patients and controls, respectively. However, when bariatric studies were excluded, BMI did not significantly explain the between-study variance.
  
  
  CONCLUSIONS
  Circulating leptin levels were higher in patients with NAFLD than in controls. Higher levels of circulating leptin were associated with increased severity of NAFLD, and the association remained significant after the exclusion of studies involving paediatric or adolescent populations and morbidly obese individuals subjected to bariatric surgery.
authors.affiliation: Second Medical Clinic, Department of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 49 Konstantinoupoleos, 546 42, Thessaloniki, Greece. stergios@endo.gr.
authors.forename: Stergios A
authors.identifier: http://orcid.org/0000-0001-9232-4042
authors.initials: SA
authors.lastname: Polyzos
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Aronis
authors.affiliation: Second Medical Clinic, Department of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 49 Konstantinoupoleos, 546 42, Thessaloniki, Greece.
authors.forename: Jannis
authors.initials: J
authors.lastname: Kountouras
authors.affiliation: Second Medical Clinic, Department of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 49 Konstantinoupoleos, 546 42, Thessaloniki, Greece.
authors.forename: Dimitrios D
authors.initials: DD
authors.lastname: Raptis
authors.affiliation: Second Medical Clinic, Department of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, 49 Konstantinoupoleos, 546 42, Thessaloniki, Greece.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Vasiloglou
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.|Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA.
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D006801:Humans; D020738:Leptin / Q000097:blood*; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood*; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D020738:Leptin
keywords: Adipokine; Adipose tissue; Insulin resistance; Leptin; Meta-analysis; Metabolic syndrome; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Steatosis; Systematic review