Dysregulation of plasma ghrelin in alcoholic cirrhosis

Abnormalities in circulating ghrelin have been reported in chronic liver disease. This study assessed the response of anabolic peptides ghrelin, growth hormone (GH) and insulin-like growth factor 1 (IGF-1) in patients with alcoholic cirrhosis and healthy subjects to oral glucose. In a previous study, using oral glucose we identified loss of ghrelin regulation in nonalcoholic steato-hepatitis. PATIENTS/DESIGN/MEASUREMENTS: Fourteen patients with alcoholic cirrhosis were compared with 11 healthy subjects. Patients with cirrhosis were studied when adjudged clinically stable in hospital. After an overnight fast, they ingested 100-g glucose dissolved in 250 ml of water. Blood was sampled before and every 20 minutes after ingestion for 120 minutes. Plasma acylated and des-acyl ghrelin, GH, IGF-1 and insulin were assayed by ELISA.

Expressed as median (95% CI): 120-minutes integrated acylated ghrelin was 26 (19-66) in controls compared to 170 (129-252) pg/ml per hour in patients with cirrhosis; P < 0.001. Both groups exhibited a normal postglucose plasma total ghrelin profile. Among patients with cirrhosis (compared to controls), growth hormone was increased 15-fold and IGF-1 decreased 4-fold. Acylated ghrelin correlated with GH (Spearman r = 0.69, P = 0.0015) in control subjects but not in patients with cirrhosis.

Acylated ghrelin is markedly increased in alcoholic cirrhosis, with apparent preservation of normal postprandial mechanisms of gastric ghrelin secretion. GH is also increased; however, its correlation with acylated ghrelin (confirmed in healthy subjects) is absent in patients with cirrhosis. Despite increased ghrelin and GH, patients with alcoholic cirrhosis remain anorexic and catabolic suggesting potential tissue resistance to the actions of these anabolic peptides.