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Horm Metab Res 2018; 50(02): 145-151
DOI: 10.1055/s-0043-118911
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Impairment of GH/IGF-1 Axis in the Liver of Patients with HCV-Related Chronic Hepatitis

Simone Carotti
1   Unit of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico, Rome, Italy
,
Michele Pier Luca Guarino
2   Unit of Digestive Disease, University Campus Bio-Medico, Rome, Italy
,
Francesco Valentini
1   Unit of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico, Rome, Italy
,
Silvio Porzio
1   Unit of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico, Rome, Italy
,
Umberto Vespasiani-Gentilucci
3   Clinical Medicine and Hepatology Unit, University Campus Bio-Medico, Rome, Italy
,
Giuseppe Perrone
4   Department of Anatomical Pathology, University Campus Bio-Medico, Rome, Italy
,
Maria Zingariello
1   Unit of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico, Rome, Italy
,
Paolo Gallo
3   Clinical Medicine and Hepatology Unit, University Campus Bio-Medico, Rome, Italy
,
Michele Cicala
2   Unit of Digestive Disease, University Campus Bio-Medico, Rome, Italy
,
Antonio Picardi
3   Clinical Medicine and Hepatology Unit, University Campus Bio-Medico, Rome, Italy
,
Sergio Morini
1   Unit of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico, Rome, Italy
› Author Affiliations
Further Information

Publication History

received 07 June 2017

accepted 17 August 2017

Publication Date:
18 September 2017 (online)

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Abstract

Resistance to the action of growth hormone (GH) frequently complicates liver cirrhosis, while, physiologically, the activation of GH receptor (GHR) determines phosphorylation of signal transducer and activator of transcription (STAT)-5 and the consequent induction of insulin-like growth factor-1 (IGF-1) expression. The suppressor of cytokine signaling (SOCS)-3 negatively regulates this intracellular cascade. We aimed to evaluate the hepatic expression of the GH/IGF-1 axis components in the liver of patients with HCV-related chronic hepatitis at different fibrosis stages. The expression of GH/IGF-1 axis components, such as GHR, IGF-1, STAT5-p, and SOCS-3, was assessed by immunohistochemistry at the lobular level in 61 patients with HCV-related hepatitis. At the hepatocyte level, IGF-1 and nuclear STAT5-p positivity scores showed negative correlations with fibrosis stage, while SOCS-3 score a positive one (p<0.05 for all). Furthermore, the reduction of hepatocyte score of IGF-1 expression was associated with the serological parameters of liver damage (p<0.05) and with the increase of the score of IGF-1 expression by hepatic stellate cells (p<0.05). IGF-1 expression by hepatocytes was reduced with fibrosis progression, probably due to the impairment of GHR intracellular cascade by the SOCS-3 activation already in pre-cirrhotic stages. The inverse correlation between IGF-1 expressed by hepatocytes and by hepatic stellate cells suggests that IGF-1 may exert specific functions in different hepatic cells.

Key words

chronic hepatitis - GH resistance - IGF-1 - liver fibrosis

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