Fibrosis P rogression in HCV C arriers with M ild H epatitis W ho P ossess the H igh‐ R epetition V ariant of the DRD 4 G ene, a G enetic M arker for B inge‐ D rinking and R isk‐ S eeking B ehavior: A L ongitudinal S tudy

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 D 4 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. 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. 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 F isher'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. 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 .