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
Article first published online: 8 JAN 2013
Copyright © 2013 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 37, Issue 6, pages 891–895, June 2013
How to Cite
Minisini, R., Boccato, E., Favretto, S., Alaimo, E., Smirne, C., Burlone, M. E., Bocchetta, S., Vandelli, C., Colletta, C., Colletta, A. and Pirisi, M. (2013), 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. Alcoholism: Clinical and Experimental Research, 37: 891–895. doi: 10.1111/acer.12047
- Issue published online: 28 MAY 2013
- Article first published online: 8 JAN 2013
- Manuscript Accepted: 23 SEP 2012
- Manuscript Received: 31 JUL 2012
- DRD4 Allele;
- Alcohol Consumption;
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.
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.
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.
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.