Fabris Carlo, Toniutto Pierluigi, Bitetto Davide, Minisini Rosalba, Smirne Carlo, Caldato Maya, Pirisi Mario
Liver Transplantation Unit, Department of Experimental and Clinical Pathology and Medicine (DPMSC), University of Udine, Italy.
Liver Int. 2005 Dec;25(6):1128-35. doi: 10.1111/j.1478-3231.2005.01156.x.
The histological outcome of chronic hepatitis C is better among carriers of the apolipoprotein E (ApoE) epsilon4 allele, for reasons unknown. The orthotopic liver transplantation (OLT) setting allows to separate the role played by liver-derived ApoE (graft) from ApoE of different origin (recipient).
Forty-six OLT recipients with recurrent hepatitis C were studied. Grafts and recipients were genotyped for ApoE. In a follow-up extending up to 4 years, the serum triglycerides-to-cholesterol ratio (T/C ratio) was measured 1 year after OLT, whereas fibrosis progression was assessed yearly and expressed as fibrosis units/month (FU/mo).
A T/C ratio < or =0.75 was observed in 13/15 cases in which both donor and recipient were epsilon4 carriers, 10/19 cases in which epsilon4 alleles were of exclusive recipient's origin and 5/12 cases in which epsilon4 alleles were of exclusive donor's origin or absent (P<0.02). One year after OLT, a fibrosis progression < or =0.100 FU/mo was associated with a low T/C ratio (24/34 vs. 4/12, P<0.05). An Ishak staging score >2 was reached later by male recipients who were epsilon4 carriers (P<0.002).
Recipient's carriage of ApoE epsilon4 affects fibrosis progression of recurrent hepatitis C through gender-specific mechanisms, associated with a peculiar, ApoE-associated, lipid profile.
载脂蛋白E(ApoE)ε4等位基因携带者的慢性丙型肝炎组织学转归较好,原因不明。原位肝移植(OLT)可区分肝源性ApoE(移植物)和不同来源的ApoE(受者)所起的作用。
对46例复发性丙型肝炎的OLT受者进行研究。对移植物和受者进行ApoE基因分型。在长达4年的随访中,OLT术后1年测量血清甘油三酯与胆固醇比值(T/C比值),而每年评估纤维化进展情况,并以纤维化单位/月(FU/mo)表示。
供者和受者均为ε4携带者的13/15例、ε4等位基因仅来源于受者的10/19例以及ε4等位基因仅来源于供者或不存在ε4等位基因的5/12例中,观察到T/C比值≤0.75(P<0.02)。OLT术后1年,纤维化进展≤0.100 FU/mo与低T/C比值相关(24/34对4/12,P<0.05)。ε4携带者男性受者达到Ishak分期评分>2的时间较晚(P<0.002)。
受者携带ApoE ε4通过性别特异性机制影响复发性丙型肝炎的纤维化进展,这与一种特殊的、与ApoE相关的血脂谱有关。