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Journal Articles Gastroentérologie Clinique et Biologique / Research and Clinics in Hepatology and Gastroenterology Year : 2007

[Steatosis, chronic hepatitis virus C infection and homocysteine]

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Abstract

Homocysteine, a sulfuric amino acid involved in methionine metabolism, belongs to the group of intracellular thiols. Hyperhomocysteinemia is frequent in the Caucasian population (more than 15%) and its role in vascular pathology has been clearly established. In hepatology, experimental data in transgenic mice deficient in homocysteine metabolism enzymes have shown the presence of severe liver steatosis with occasional steatohepatitis. In human beings, many studies have found a correlation between homocysteine and steatosis or even NASH. Some authors have suggested a discriminating threshold to differentiate simple steatosis from NASH. In chronic hepatitis C, preliminary data have shown that hyperhomocysteinemia is an independent risk factor for steatosis or even fibrosis. The physiopathological mechanism has now begun to be better understood. On one hand, there is a strong correlation between homocysteine and insulin resistance whatever its etiology. On the other hand, homocysteine has a direct effect on the liver, resulting in over expression of SREBP-1 and favouring steatosis. It stimulates proinflammatory cytokine secretion such as NF kappa B increasing the risk of NASH. Finally, homocysteine could increase the risk of fibrosis by stimulating TIMP 1. Moreover hepatitis C virus induces hypomethylation of STAT 1 and could decrease the antiviral activity of interferon. Results from in vitro studies have shown that the normalisation of STAT 1 methylation by bringing betaine and S Adenosyl Methionine (which belongs to homocysteine cycle) restores the antiviral activity of interferon. These data should be confirmed to evaluate the importance of homocysteine dosage in the diagnosis of NASH. Finally, treatment of hyperhomocysteinemia could have favourable consequences in steatopathies and HCV infection.
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Dates and versions

inserm-00324958 , version 1 (25-09-2008)

Identifiers

  • HAL Id : inserm-00324958 , version 1
  • PUBMED : 17483780

Cite

Xavier Roblin, Joanna Pofelski, Jean-Pierre Zarski. [Steatosis, chronic hepatitis virus C infection and homocysteine]. Gastroentérologie Clinique et Biologique / Research and Clinics in Hepatology and Gastroenterology, 2007, 31 (4), pp.415-20. ⟨inserm-00324958⟩

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