The liver diseases of lipodystrophy: The long-term effect of leptin treatment

• Published in: Journal of hepatology 2013-07, Vol.59 (1), p.131-137
• Main Authors: Safar Zadeh, Elika, Lungu, Andreea O, Cochran, Elaine K, Brown, Rebecca J, Ghany, Marc G, Heller, Theo, Kleiner, David E, Gorden, Phillip
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Alanine Transaminase - blood; Aspartate Aminotransferases - blood; Child; Cohort Studies; Fatty Liver - drug therapy; Fatty Liver - etiology; Fatty Liver - pathology; Female; Gastroenterology and Hepatology; Hepatitis, Autoimmune - drug therapy; Hepatitis, Autoimmune - etiology; Hepatitis, Autoimmune - pathology; Humans; Leptin; Leptin - analogs & derivatives; Leptin - therapeutic use; Lipodystrophy; Lipodystrophy - complications; Lipodystrophy - drug therapy; Lipodystrophy - pathology; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Metabolic syndrome; Metabolome - drug effects; Middle Aged; Non-alcoholic Fatty Liver Disease; Non-alcoholic steatohepatitis; Prospective Studies; Recombinant Proteins - therapeutic use; Young Adult
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2013.02.007

Background & Aims Lipodystrophies are hypoleptinemic conditions characterized by fat loss, severe insulin resistance, hypertriglyceridemia, and ectopic fat accumulation. Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are also features of this condition. We studied the spectrum of liver disease in lipodystrophy and the effects of leptin replacement. Methods This was an open-label, prospective study of leptin therapy in patients with inherited and acquired lipodystrophy at the National Institutes of Health. Liver biopsies were performed at baseline (N = 50) and after leptin replacement (N = 27). NASH activity was assessed using the NASH Clinical Research Network (CRN) scoring system. Fasting blood glucose, triglyceride, hemoglobin A1c and liver enzymes were measured at baseline and at the time of the final liver biopsy. Results In leptin-treated patients, 86% met criteria for NASH at baseline, while only 33% had NASH after leptin replacement for 25.8 ± 3.7 months (mean ± SE, p = 0.0003). There were significant improvements in steatosis grade (reduction of mean score from 1.8 to 0.9) and ballooning injury scores (from 1.2 to 0.4), with a 44.2% reduction in mean NAFLD activity score ( p