Apolipoprotein E genotypes modulate fibrosis progression in patients with chronic hepatitis C and persistently normal transaminases

J Gastroenterol Hepatol. 2011 Feb;26(2):328-33. doi: 10.1111/j.1440-1746.2010.06403.x.

Abstract

Background and aim: Carriage of the apolipoprotein E (Apo E) variants, E2, E3 and E4, affects cholesterol metabolism and may be involved in the persistence of hepatitis C virus (HCV) infection. Our aim was to verify whether carriage of specific Apo E variants modulates the course of hepatitis C.

Methods: We studied a cohort of 116 HCV-positive patients (49 male subjects) with persistently normal transaminases and an Ishak staging score ≤ 2 at an initial biopsy. These untreated patients underwent regular clinical monitoring (median histological follow up: 10 years). Apo E variants were genotyped and results were related to the histological outcome.

Results: The mean ± standard deviation staging scores were 0.9 ± 0.7 at entry versus 1.9 ± 1.2 at the end of follow up, P < 0.0001. Initial and final staging scores in the E3/E3 homozygotes (n = 74) were 1.0 ± 0.7 versus 2.1 ± 1.3, P < 0.0001, while in the remaining patients (n = 42) they were 0.9 ± 0.6 versus 1.5 ± 1.0, P < 0.002. A synergistic effect was observed between Apo E polymorphisms and baseline serum cholesterol values: patients not carrying any E3 allele, as well as carriers of a single E3 allele with serum cholesterol concentration > 190 mg/dL were more likely to have a favorable outcome (final vs initial staging score increased in 7/66, did not change in 10/46, and decreased in 3/4, P <0.005).

Conclusions: Some of the variability in the natural history of patients with persistently normal transaminases with initially mild hepatitis C can be related to their Apo E genetic background.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alanine Transaminase / blood*
  • Apolipoproteins E / genetics*
  • Biomarkers / blood
  • Biopsy
  • Body Mass Index
  • Chi-Square Distribution
  • Child
  • Cholesterol / blood
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Hepatitis C, Chronic / enzymology
  • Hepatitis C, Chronic / ethnology
  • Hepatitis C, Chronic / genetics*
  • Humans
  • Italy
  • Liver Cirrhosis / enzymology
  • Liver Cirrhosis / ethnology
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / virology
  • Logistic Models
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic*
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • White People / genetics
  • Young Adult

Substances

  • Apolipoproteins E
  • Biomarkers
  • Cholesterol
  • Alanine Transaminase