Low fibrosis progression of recurrent hepatitis C in apolipoprotein E ε4 carriers: Relationship with the blood lipid profile

Background: The histological outcome of chronic hepatitis C is better among carriers of the apolipoprotein E (ApoE) ε4 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). Patients and methods: 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). Results: A T/C ratio ≤0.75 was observed in 13/15 cases in which both donor and recipient were ε4 carriers, 10/19 cases in which ε4 alleles were of exclusive recipient's origin and 5/12 cases in which ε4 alleles were of exclusive donor's origin or absent (P<0.02). One year after OLT, a fibrosis progression ≤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 ε4 carriers (P<0.002). Conclusions: Recipient's carriage of ApoE ε4 affects fibrosis progression of recurrent hepatitis C through gender-specific mechanisms, associated with a peculiar, ApoE-associated, lipid profile.