Lower levels of insulin-like growth factor-1 standard deviation score are associated with histological severity of non-alcoholic fatty liver disease
Corresponding Author
Yoshio Sumida
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Correspondence: Dr Yoshio Sumida, Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. Email: [email protected]Search for more papers by this authorYoshikazu Yonei
Anti-Aging Medical Research Center, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan
Search for more papers by this authorSaiyu Tanaka
Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan
Search for more papers by this authorKojiroh Mori
Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan
Search for more papers by this authorKazuyuki Kanemasa
Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan
Search for more papers by this authorShunsuke Imai
Department of Pathology, Nara City Hospital, Nara, Japan
Search for more papers by this authorHiroyoshi Taketani
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorTasuku Hara
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorYuya Seko
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorHiroshi Ishiba
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorAkira Okajima
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorKanji Yamaguchi
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorMichihisa Moriguchi
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorHironori Mitsuyoshi
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorKohichiroh Yasui
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorMasahito Minami
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorYoshito Itoh
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorCorresponding Author
Yoshio Sumida
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Correspondence: Dr Yoshio Sumida, Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. Email: [email protected]Search for more papers by this authorYoshikazu Yonei
Anti-Aging Medical Research Center, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan
Search for more papers by this authorSaiyu Tanaka
Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan
Search for more papers by this authorKojiroh Mori
Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan
Search for more papers by this authorKazuyuki Kanemasa
Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan
Search for more papers by this authorShunsuke Imai
Department of Pathology, Nara City Hospital, Nara, Japan
Search for more papers by this authorHiroyoshi Taketani
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorTasuku Hara
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorYuya Seko
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorHiroshi Ishiba
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorAkira Okajima
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorKanji Yamaguchi
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorMichihisa Moriguchi
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorHironori Mitsuyoshi
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorKohichiroh Yasui
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorMasahito Minami
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorYoshito Itoh
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Search for more papers by this authorAbstract
Aim
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.
Conclusion
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.
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