Circulating leptin in non-alcoholic fatty liver disease: a systematic review and meta-analysis

Abstract

Aims/hypothesis 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-tosevere 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/interpretation 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.

Pathophysiology of Non Alcoholic Fatty Liver Disease

“…A recent meta-analysis indicates that circulating leptin levels are higher in patients with NAFLD than in controls, and higher serum leptin levels were associated with an increased severity of NAFLD [81]. This is in agreement with the above-mentioned evidence of inflammatory-mediated damage related to leptin and potential involvement in NASH pathogenesis.…”

Nonalcoholic Fatty Liver Disease Is Not Associated with Thyroid Hormone Levels and Hypothyroidism: A Systematic Review and Meta-Analysis

“…Leptin is considered as one of the explanations of this association because it is found to be increased in patients with hypothyroidism [28] and it is also found to be higher in NAFLD as it can promote hepatic insulin resistance and be involved in hepatic fibrogenesis [29,30]. Fibroblast growth factor-21, a member of fibroblast growth factor family, could also provide a role in this association as increased serum fibroblast growth factor-21 levels were observed in patients with hypothyroidism [31].…”

The Possible Role of Helicobacter pylori Infection in Non-alcoholic Fatty Liver Disease

“…Studies suggested that the levels of plasma leptin were elevated in NAFLD group (Friedman, 2008), and it is an independent predictor of hepatic steatosis (Chitturi et al, 2002; Polyzos et al, 2016). A study involving 153 dyspeptic patients, found that H. pylori infection was significantly negatively associated with serum leptin level ( P < 0.001).…”