Apolipoprotein E genotypes modulate fibrosis progression in patients with chronic hepatitis C and persistently normal transaminases.
OBJECTIVE
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.
Medical Liver Transplant Unit, Department of Medical Sciences, Clinical and Experimental, University of Udine, Udine, Italy.
Carlo
C
Fabris
Carmen
C
Vandelli
Pierluigi
P
Toniutto
Rosalba
R
Minisini
Cosimo
C
Colletta
Edmondo
E
Falleti
Carlo
C
Smirne
Mario
M
Pirisi
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D001057:Apolipoproteins E / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015992:Body Mass Index; D016009:Chi-Square Distribution; D002648:Child; D002784:Cholesterol / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D019698:Hepatitis C, Chronic / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007558:Italy; D008103:Liver Cirrhosis / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000821:virology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D044465:White People / Q000235:genetics; D055815:Young Adult
D001057:Apolipoproteins E; D015415:Biomarkers; D002784:Cholesterol; D000410:Alanine Transaminase