title: The Association Between IGF-1 Levels and the Histologic Severity of Nonalcoholic Fatty Liver Disease.
abstract: OBJECTIVE
  The mechanisms responsible for the development of nonalcoholic fatty liver disease (NAFLD) and progression to nonalcoholic steatohepatitis (NASH) are incompletely understood. Growing evidence suggests that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may have roles in the development and progression of NAFLD. We hypothesized that lower serum IGF-1 levels would be associated with increased liver fat accumulation, inflammation, and fibrosis in a group of meticulously phenotyped obese subjects with liver biopsies.
  
  
  METHODS
  A retrospective, cross-sectional study was performed at Massachusetts General Hospital, Boston, MA, USA and St. Mary's Hospital, Richmond, VA, USA. Liver biopsies were performed in 142 subjects during NAFLD work-up or bariatric surgery and were graded by a single, blinded pathologist. Main outcome measures included liver histology and serum IGF-1.
  
  
  RESULTS
  Mean age was 52±10 years and body mass index (BMI) was 43±9 kg/m2. Mean serum IGF-1 was lower in subjects with lobular inflammation (112±47 vs. 136±57 ng/ml, P=0.01), hepatocyte ballooning (115±48 vs. 135±57 ng/ml, P=0.05), higher fibrosis stage (stage 2-4 vs. 0-1; 96±40 vs. 125±51 ng/ml, P=0.005), and NASH (109±45 vs. 136±57 ng/ml, P=0.002). All results remained significant after controlling for age, BMI, and a diagnosis of diabetes, and all but hepatocyte ballooning (trend, P=0.06) remained significant after excluding individuals with cirrhosis. Steatosis was not significantly associated with mean serum IGF-1 levels.
  
  
  CONCLUSIONS
  Low serum IGF-1 levels are associated with increased histologic severity of NAFLD when rigorously controlled for age, BMI, the presence of diabetes, and after the exclusion of subjects with cirrhosis. Further investigation is warranted to determine the differential effects of GH and IGF-1 on the development and progression of NAFLD, which could further elucidate pathophysiology and identify therapeutic targets.
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Dichtel
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Corey
authors.affiliation: Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Misdraji
authors.affiliation: Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Miriam A
authors.initials: MA
authors.lastname: Bredella
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Schorr
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Osganian
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Young
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Sung
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Karen K
authors.initials: KK
authors.lastname: Miller