Toniutto Pierluigi, Fabris Carlo, Falleti Edmondo, Cussigh Annarosa, Fontanini Elisabetta, Bitetto Davide, Fornasiere Ezio, Minisini Rosalba, De Feo Tullia, Marangoni Francesca, Pirisi Mario
Department of Pathology and Medicine Experimental and Clinical, Medical Liver Transplant Unit, University of Udine, Udine, Italy.
Liver Int. 2008 Feb;28(2):257-63. doi: 10.1111/j.1478-3231.2007.01591.x. Epub 2007 Sep 26.
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).
We studied 63 such patients, followed for >1 year. MTHFR allelic variants were determined by a polymerase chain reaction/restriction fragment length polymorphism method.
Recipients carrying the TT genotype had more frequently, 1-year post-OLT, homocysteine serum levels >23 micromol/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 < or =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).
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.
背景/目的:亚甲基四氢叶酸还原酶(MTHFR)C677T多态性作为一种假定的致脂肪变性因素,可能会促进慢性丙型肝炎患者肝纤维化的进展。本研究旨在验证受体MTHFR多态性在原位肝移植(OLT)后复发性丙型肝炎患者移植肝纤维化进展中的作用。
我们研究了63例此类患者,随访时间超过1年。通过聚合酶链反应/限制性片段长度多态性方法确定MTHFR等位基因变异。
携带TT基因型的受体在OLT术后1年时,更频繁地出现血清同型半胱氨酸水平>23微摩尔/升(P<0.05)、血清甘油三酯>180毫克/分升(P<0.02)和新发糖尿病(P<0.05),但移植肝脂肪变性的发生率并未更高。通过将受体分为以下几组进行达到Ishak分期评分>2的事件发生时间分析:(a)供体年龄≤45岁的患者,(b)供体年龄>45岁且为C/(*)基因型的患者,以及(c)供体年龄>45岁且为TT基因型的患者。观察到显著的线性趋势,频率增加如下:(a)8/37,(b)10/19,(c)6/7(P=0.0005)。
MTHFR C677T多态性可能与供体年龄一起,在影响复发性丙型肝炎患者肝纤维化进展中起作用,但不是通过促进脂肪变性。