Methylenetetrahydrofolate reductase C677T polymorphism and liver fibrosis progression in patients with recurrent hepatitis C

Authors

  • Pierluigi Toniutto,

    1. Department of Pathology and Medicine Experimental and Clinical, Medical Liver Transplant Unit, University of Udine, Udine, Italy
    Search for more papers by this author
  • Carlo Fabris,

    1. Department of Pathology and Medicine Experimental and Clinical, Medical Liver Transplant Unit, University of Udine, Udine, Italy
    Search for more papers by this author
  • Edmondo Falleti,

    1. Department of Pathology and Medicine Experimental and Clinical, Medical Liver Transplant Unit, University of Udine, Udine, Italy
    Search for more papers by this author
  • Annarosa Cussigh,

    1. Department of Pathology and Medicine Experimental and Clinical, Medical Liver Transplant Unit, University of Udine, Udine, Italy
    Search for more papers by this author
  • Elisabetta Fontanini,

    1. Department of Pathology and Medicine Experimental and Clinical, Medical Liver Transplant Unit, University of Udine, Udine, Italy
    Search for more papers by this author
  • Davide Bitetto,

    1. Department of Pathology and Medicine Experimental and Clinical, Medical Liver Transplant Unit, University of Udine, Udine, Italy
    Search for more papers by this author
  • Ezio Fornasiere,

    1. Department of Pathology and Medicine Experimental and Clinical, Medical Liver Transplant Unit, University of Udine, Udine, Italy
    Search for more papers by this author
  • Rosalba Minisini,

    1. Department of Clinical and Experimental Medicine, University of Eastern Piedmont ‘Amedeo Avogadro', Novara, Italy
    2. Interdisciplinary Research Center on Autoimmune Diseases (IRCAD), University of Eastern Piedmont ‘Amedeo Avogadro’, Novara, Italy
    Search for more papers by this author
  • Tullia De Feo,

    1. North Italy Transplant Program – IRCCS Fondazione Ospedale Maggiore, Milano, Italy
    Search for more papers by this author
  • Francesca Marangoni,

    1. North Italy Transplant Program – IRCCS Fondazione Ospedale Maggiore, Milano, Italy
    Search for more papers by this author
  • Mario Pirisi

    1. Department of Clinical and Experimental Medicine, University of Eastern Piedmont ‘Amedeo Avogadro', Novara, Italy
    2. Interdisciplinary Research Center on Autoimmune Diseases (IRCAD), University of Eastern Piedmont ‘Amedeo Avogadro’, Novara, Italy
    Search for more papers by this author

Correspondence
Pierluigi Toniutto, MD, Internal Medicine, Medical Liver Transplantation Unit, University of Udine, Piazzale S. M. della Misericordia 1; 33100 Udine, Italy
Tel: +39/0432559802
Fax: +39/043242097
e-mail: pierluigi.toniutto@uniud.it

Abstract

Background/Aims: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, being a putative steatogenic factor, may promote liver fibrosis progression in patients with chronic hepatitis C. This study aimed to verify the role of recipient MTHFR polymorphism in favouring graft fibrosis progression in patients with recurrent HCV after orthotopic liver transplantation (OLT).

Methods: We studied 63 such patients, followed for >1 year. MTHFR allelic variants were determined by a polymerase chain reaction/restriction fragment length polymorphism method.

Results: Recipients carrying the TT genotype had more frequently, 1-year post-OLT, homocysteine serum levels >23 μmol/L (P<0.05), serum triglycerides >180 mg/dL (P<0.02) and de novo diabetes mellitus (P<0.05) but not a higher frequency of graft steatosis. Time-to-event analysis in reaching an Ishak staging score >2 was performed by stratifying the recipients as follows: (a) patients with donor age ≤45 years, (b) patients with donor age >45 and C/* genotype, and (c) patients with donor age >45 years and TT genotype. A significant linear trend was observed, with increasing frequencies as follows: (a) 8/37, (b) 10/19 and (c) 6/7 (P=0.0005).

Conclusion: The MTHFR C677T polymorphism may play a role in influencing liver fibrosis progression in patients with recurrent hepatitis C, in conjunction with donor age, but not via steatosis promotion.

Ancillary