title: 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.
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.
  
  
  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 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.
  
  
  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.
authors.affiliation: Department of Translational Medicine , Università del Piemonte Orientale Amedeo Avogadro, Novara, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Minisini
authors.forename: Elisa
authors.initials: E
authors.lastname: Boccato
authors.forename: Serena
authors.initials: S
authors.lastname: Favretto
authors.forename: Emanuele
authors.initials: E
authors.lastname: Alaimo
authors.forename: Carlo
authors.initials: C
authors.lastname: Smirne
authors.forename: Michela E
authors.initials: ME
authors.lastname: Burlone
authors.forename: Simone
authors.initials: S
authors.lastname: Bocchetta
authors.forename: Carmen
authors.initials: C
authors.lastname: Vandelli
authors.forename: Cosimo
authors.initials: C
authors.lastname: Colletta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Colletta
authors.forename: Mario
authors.initials: M
authors.lastname: Pirisi
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000473:pathology; D063425:Binge Drinking / Q000235:genetics; D001706:Biopsy; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D005787:Gene Frequency; D019698:Hepatitis C, Chronic / Q000150:complications / Q000473:pathology*; D008103:Liver Cirrhosis / Q000150:complications / Q000473:pathology*; D008137:Longitudinal Studies; D018598:Minisatellite Repeats / Q000235:genetics; D015999:Multivariate Analysis; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012307:Risk Factors; D012309:Risk-Taking; D057566:Self Report; D012720:Severity of Illness Index
chemical_list: C493599:DRD4 protein, human; D050638:Receptors, Dopamine D4