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

Simone Carotti; Michele Pier Luca Guarino; Francesco Valentini; Silvio Porzio; Umberto Vespasiani-Gentilucci; Giuseppe Perrone; Maria Zingariello; Paolo Gallo; Michele Cicala; Antonio Picardi; Sergio Morini

doi:10.1055/s-0043-118911

Hormone and Metabolic Research, Inhaltsverzeichnis

Horm Metab Res 2018; 50(02): 145-151
DOI: 10.1055/s-0043-118911

Endocrine Research

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

Autor*innen

Simone Carotti

¹Unit of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico, Rome, Italy
Michele Pier Luca Guarino

²Unit of Digestive Disease, University Campus Bio-Medico, Rome, Italy
Francesco Valentini

¹Unit of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico, Rome, Italy
Silvio Porzio

¹Unit of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico, Rome, Italy
Umberto Vespasiani-Gentilucci

³Clinical Medicine and Hepatology Unit, University Campus Bio-Medico, Rome, Italy
Giuseppe Perrone

⁴Department of Anatomical Pathology, University Campus Bio-Medico, Rome, Italy
Maria Zingariello

¹Unit of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico, Rome, Italy
Paolo Gallo

³Clinical Medicine and Hepatology Unit, University Campus Bio-Medico, Rome, Italy
Michele Cicala

²Unit of Digestive Disease, University Campus Bio-Medico, Rome, Italy
Antonio Picardi

³Clinical Medicine and Hepatology Unit, University Campus Bio-Medico, Rome, Italy
Sergio Morini

¹Unit of Microscopic and Ultrastructural Anatomy, University Campus Bio-Medico, Rome, Italy

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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Referenzen

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