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Fibrosis progression in HCV carriers with mild hepatitis who possess the high-repetition variant of the DRD4 gene, a genetic marker for binge-drinking and risk-seeking behavior: a longitudinal study.
- Source :
-
Alcoholism, clinical and experimental research [Alcohol Clin Exp Res] 2013 Jun; Vol. 37 (6), pp. 891-5. Date of Electronic Publication: 2013 Jan 08. - Publication Year :
- 2013
-
Abstract
- Background: Alcohol is a major determinant of the outcome of chronic hepatitis C virus (HCV) infection, but self-reported drinking habits lack reliability. We hypothesized that carriage of high-repetition variants (HRV) of the variable number of tandem repeats (VNTR) in exon III of the dopamine receptor D4 gene, linked to binge-drinking and risk-seeking behavior, might be a proxy measure of alcohol consumption, and aimed to verify whether it may affect histologic outcome.<br />Methods: A cohort of HCV patients with normal or near-normal aminotransferases (N = 128) underwent a liver biopsy as part of diagnostic work-up. None admitted to exceed low-risk alcohol consumption; most (90/128, 70%) described themselves as teetotalers. They received advice on abstaining from alcohol, but not antiviral treatment. After a median follow-up period of 10 years, all underwent a second liver biopsy. HRV allele frequencies were compared with those of a group of healthy blood donors (N = 128) and related to liver histology.<br />Results: HRV allele frequencies were 0.19 in patients and 0.16 in controls (p = 0.182). In the subgroup of patients who admittedly had consumed alcohol, 20/38 (53%) carried HRV, in comparison with 27/90 patients (30%) who had denied to consume alcohol (p = 0.026 by Fisher's exact test). Carriage of HRV was associated with higher histologic grade (p = 0.002) and stage (p = 0.009) at the final biopsy. At multivariate analysis, among a set of variables also including viral genotype, viral load, body mass index, gender, and history of alcohol consumption, only age (OR = 1.06, 95% CI 1.02 to 1.11) and HRV (OR = 3.13, 95% CI 1.28 to 7.68) were independent predictors of significant fibrosis at the end of follow-up.<br />Conclusions: The link between HRV carriage and histologic outcome in a subgroup of HCV patients at low risk of progression underlines the need for intense scrutiny of alcohol habits in hepatitis C.<br /> (Copyright © 2013 by the Research Society on Alcoholism.)
- Subjects :
- Alcohol Drinking pathology
Binge Drinking genetics
Biopsy
Case-Control Studies
Cohort Studies
Disease Progression
Gene Frequency
Hepatitis C, Chronic complications
Liver Cirrhosis complications
Longitudinal Studies
Minisatellite Repeats genetics
Multivariate Analysis
Risk Factors
Risk-Taking
Severity of Illness Index
Alcohol Drinking genetics
Hepatitis C, Chronic pathology
Liver Cirrhosis pathology
Receptors, Dopamine D4 genetics
Self Report
Subjects
Details
- Language :
- English
- ISSN :
- 1530-0277
- Volume :
- 37
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Alcoholism, clinical and experimental research
- Publication Type :
- Academic Journal
- Accession number :
- 23298155
- Full Text :
- https://doi.org/10.1111/acer.12047