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

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: 10years). 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±0.7versus 2.1±1.3, P<0.0001, while in the remaining patients (n=42) they were 0.9±0.6versus 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 >190mg/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.