title: Lower levels of insulin-like growth factor-1 standard deviation score are associated with histological severity of non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  Growth hormone (GH) deficiency may be associated with histological progression of non-alcoholic fatty liver disease (NAFLD) which includes non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Insulin-like growth factor 1 (IGF-1) is mainly produced by hepatocytes and its secretion is stimulated by GH. Our aim was to determine whether more histologically advanced NAFLD is associated with low circulating levels of IGF-1 in Japanese patients.
  
  
  METHODS
  Serum samples were obtained in 199 Japanese patients with biopsy-proven NAFLD and in 2911 sex- and age-matched healthy people undergoing health checkups. The serum levels of IGF-1 were measured using a commercially available immunoradiometric assay. The standard deviation scores (SDS) of IGF-1 according to age and sex were also calculated in NAFLD patients.
  
  
  RESULTS
  The serum IGF-1 levels in NAFLD patients were significantly lower (median, 112 ng/mL) compared with the control population (median, 121 ng/mL, P < 0.0001). IGF-1 SDS less than -2.0 SD from median were found in 11.6% of 199 patients. NASH patients exhibited significantly lower levels of IGF-1 SDS (n = 130; median, -0.7) compared with NAFL patients (n = 69; median, -0.3; P = 0.026). The IGF-1 SDS values decreased significantly with increasing lobular inflammation (P < 0.001) and fibrosis (P < 0.001). In multiple regressions, the association between the IGF-1 SDS values and the severity of NAFLD persisted after adjusting for age, sex and insulin resistance.
  
  
  CONCLUSIONS
  Low levels of circulating IGF-1 may have a role in the development of advanced NAFLD, independent of insulin resistance. Supplementation with GH/IGF-1 may be a candidate for the treatment of NASH.
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Sumida
authors.affiliation: Anti-Aging Medical Research Center, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yonei
authors.affiliation: Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan.
authors.forename: Saiyu
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan.
authors.forename: Kojiroh
authors.initials: K
authors.lastname: Mori
authors.affiliation: Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kanemasa
authors.affiliation: Department of Pathology, Nara City Hospital, Nara, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Imai
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Taketani
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Hara
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Seko
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishiba
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Okajima
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Michihisa
authors.initials: M
authors.lastname: Moriguchi
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Mitsuyoshi
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kohichiroh
authors.initials: K
authors.lastname: Yasui
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Minami
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Itoh
keywords: fibrosis; insulin like growth factor-1; insulin resistance; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis