Circulating leptin in non-alcoholic fatty liver disease: a systematic review and meta-analysis
BACKGROUND/AIMS Leptin is a peptide which regulates food intake and energy expenditure. Moreover, it is involved in the homeostasis of body composition and is linked to the regulation of insulin signaling, thus playing an important role in liver fat storage. Steatosis is a common finding in chronic hepatitis C, and both viral and metabolic factors have been suggested to explain the presence of this histological characteristic. In order to study leptin in chronic liver disease characterized by the presence of steatosis, we evaluated its serum levels in patients with nonalcoholic steatohepatitis (NASH), in chronic hepatitis C (CHC) patients with no histological findings of steatosis, and CHC patients with steatosis but no risk factors for its development. METHODOLOGY We studied 6 male patients with NASH whose diagnosis was made on the basis of histological findings and clinical criteria. From among a cohort of 170 CHC patients we put together 2 groups of 6 male patients each (with or without steatosis at liver biopsy examination), who had no risk factors for NASH. Male patients were chosen in order to avoid gender influence on leptin levels. Further criteria for admission were similar impairment of liver metabolic function as assessed by the monoethylglycinexylidide (MEGX) test and, in patients with CHC, similar body mass index (BMI) and histological staging. Moreover, we evaluated leptin/BMI ratio, in order to rule out BMI influence on leptin levels. Leptin levels were assessed by means of radioimmunoassay. RESULTS We found that BMI was higher in NASH compared to CHC (27.2 +/- 2.9 vs. 23.9 +/- 1.8; p = 0.01). Analysis of serum leptin levels showed an increasing trend starting from patients with CHC without steatosis (3.2 +/- 0.4 ng/ml), through CHC patients with steatosis (4.2 +/- 0.7 ng/ml) up to patients with NASH (5.7 +/- 2 ng/ml), although the differences observed were not statistically significant. Moreover, the ratio of leptin to BMI also followed the same trend showing increasing values (CHC without steatosis = 0.04 +/- 0.02; CHC patients with steatosis = 0.17 +/- 0.03; NASH = 0.203 +/- 0.07). Leptin levels and BMI showed a significant relationship (n = 18; r = 0.60; p < 0.01). CONCLUSIONS The increasing trend observed in leptin serum levels among the different groups of patients showed that in chronic liver disease characterized by the presence of steatosis, leptin signaling is preserved. Moreover, CHC factors different from the metabolic ones should be investigated in order to explain the presence of steatosis. Further studies on broader groups of patients are needed to verify these preliminary results.