title: The liver diseases of lipodystrophy: the long-term effect of leptin treatment.
abstract: OBJECTIVE
  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<0.0001). Patients who already had fibrosis remained stable on leptin replacement. We observed significant improvement in metabolic profile, ALT and AST. In addition to NASH, four patients with acquired generalized lipodystrophy (AGL) had autoimmune hepatitis.
  
  
  CONCLUSIONS
  The fundamental liver disease of lipodystrophy is NASH, although autoimmune hepatitis was observed in some patients with AGL. Leptin appears to be a highly effective therapy for NASH in hypoleptinemic lipodystrophic patients.
authors: Diabetes Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.
authors: Elika
authors: E
authors: Safar Zadeh
authors: Andreea O
authors: AO
authors: Lungu
authors: Elaine K
authors: EK
authors: Cochran
authors: Rebecca J
authors: RJ
authors: Brown
authors: Marc G
authors: MG
authors: Ghany
authors: Theo
authors: T
authors: Heller
authors: David E
authors: DE
authors: Kleiner
authors: Phillip
authors: P
authors: Gorden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D002648:Child; D015331:Cohort Studies; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D005260:Female; D019693:Hepatitis, Autoimmune / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D006801:Humans; D020738:Leptin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008060:Lipodystrophy / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D055442:Metabolome / Q000187:drug effects; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D020738:Leptin; D011994:Recombinant Proteins; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C415771:metreleptin