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
Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
Medientyp:
E-Artikel
Titel:
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
Beschreibung:
<jats:sec><jats:title>Background</jats:title><jats:p>Alcohol is a major determinant of the outcome of chronic hepatitis <jats:styled-content style="fixed-case">C</jats:styled-content> virus (<jats:styled-content style="fixed-case">HCV</jats:styled-content>) infection, but self‐reported drinking habits lack reliability. We hypothesized that carriage of high‐repetition variants (<jats:styled-content style="fixed-case">HRV</jats:styled-content>) of the variable number of tandem repeats (<jats:styled-content style="fixed-case">VNTR</jats:styled-content>) in exon <jats:styled-content style="fixed-case">III</jats:styled-content> of the dopamine receptor D<jats:sub>4</jats:sub> 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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A cohort of <jats:styled-content style="fixed-case">HCV</jats:styled-content> patients with normal or near‐normal aminotransferases (<jats:italic>N</jats:italic> = 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. <jats:styled-content style="fixed-case">HRV</jats:styled-content> allele frequencies were compared with those of a group of healthy blood donors (<jats:italic>N</jats:italic> = 128) and related to liver histology.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>HRV allele frequencies were 0.19 in patients and 0.16 in controls (<jats:italic>p</jats:italic> = 0.182). In the subgroup of patients who admittedly had consumed alcohol, 20/38 (53%) carried <jats:styled-content style="fixed-case">HRV</jats:styled-content>, in comparison with 27/90 patients (30%) who had denied to consume alcohol (<jats:italic>p</jats:italic> = 0.026 by <jats:styled-content style="fixed-case">F</jats:styled-content>isher's exact test). Carriage of <jats:styled-content style="fixed-case">HRV</jats:styled-content> was associated with higher histologic grade (<jats:italic>p</jats:italic> = 0.002) and stage (<jats:italic>p</jats:italic> = 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 (<jats:styled-content style="fixed-case">OR</jats:styled-content> = 1.06, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 1.02 to 1.11) and <jats:styled-content style="fixed-case">HRV</jats:styled-content> (<jats:styled-content style="fixed-case">OR</jats:styled-content> = 3.13, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 1.28 to 7.68) were independent predictors of significant fibrosis at the end of follow‐up.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The link between <jats:styled-content style="fixed-case">HRV</jats:styled-content> carriage and histologic outcome in a subgroup of <jats:styled-content style="fixed-case">HCV</jats:styled-content> patients at low risk of progression underlines the need for intense scrutiny of alcohol habits in hepatitis <jats:styled-content style="fixed-case">C</jats:styled-content>.</jats:p></jats:sec>