title: Growth hormone, dehydroepiandrosterone and adiponectin levels in non-alcoholic steatohepatitis: an endocrine signature for advanced fibrosis in obese patients.
abstract: OBJECTIVE
  Liver-related clinical consequences of non-alcoholic fatty liver disease (NAFLD) are seen only in the minority of patients with advanced fibrosis. The aim of our study was to generate insight into a potential endocrine basis of steatohepatitis with advanced fibrosis in NAFLD.
  
  
  METHODS
  Biopsy and blood samples were prospectively collected from patients with medically complicated obesity. Patients were categorized, according to liver histology, into: (i) normal, (ii) simple steatosis (SS), (iii) non-alcoholic steatohepatitis (NASH) with fibrosis stage (FS) 0-1 and (iv) NASH with FS ≥ 2. A broad panel of potential biomarkers included DHEA-S, growth hormone (GH), homeostasis model assessment-insulin resistance (HOMA-IR), leptin, resistin, adiponectin and cytokeratin 18 (CK-18) fragments.
  
  
  RESULTS
  We studied 160 patients (mean BMI 46.8 ± 8.2 kg/m(2) ). Liver biopsies demonstrated normal histology in 10%, SS in 45%, NASH with FS 0-1 in 37.5% and NASH with FS ≥ 2 in 7.5%. C-reactive protein, IL-6, GH, CK-18, adiponectin, HOMA-IR and quantitative insulin sensitivity check index (QUICKI) were significantly associated with NASH in univariate analysis, but overall predictivity of these parameters was low (AUC ROC = 0.62-0.68). In contrast, all patients with NASH with FS ≥ 2 had insulin resistance, as measured by QUICKI, and GH levels <0.45 ng/ml and all but one patient with NASH FS 2-3 had low DHEA levels (<123 μg/dl).
  
  
  CONCLUSIONS
  Low serum levels of GH and DHEA are very common in patients with NASH with more advanced fibrosis. Other biomarkers, including CK-18 fragment levels, have predictivity characteristics that would be of low clinical utility for distinguishing patients with normal histology or SS from those with NASH. These findings demonstrate an endocrine profile associated with advanced fibrosis.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Edith
authors.initials: E
authors.lastname: Koehler
authors.forename: James
authors.initials: J
authors.lastname: Swain
authors.forename: Schuyler
authors.initials: S
authors.lastname: Sanderson
authors.forename: Anuradha
authors.initials: A
authors.lastname: Krishnan
authors.forename: Kymberly
authors.initials: K
authors.lastname: Watt
authors.forename: Michael
authors.initials: M
authors.lastname: Charlton
mesh_terms: D052242:Adiponectin / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003687:Dehydroepiandrosterone / Q000097:blood*; D005234:Fatty Liver / Q000097:blood*; D005260:Female; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity; D012720:Severity of Illness Index
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D003687:Dehydroepiandrosterone; D013006:Growth Hormone