title: Antinuclear antibodies (ANA) in chronic hepatitis C virus infection: correlates of positivity and clinical relevance.
abstract: We examined correlates of antinuclear antibody (ANA) positivity (ANA+) in individuals with chronic hepatitis C virus (HCV) infection and the effect of positivity on clinical outcome of HCV. Pretreatment sera from 645 patients from three centres in Sweden (n = 225), the UK (n = 207) and Italy (n = 213) were evaluated by indirect immunofluorescence on Hep-2 cells for ANA pattern and titre by a single laboratory. Liver biopsies were all scored by one pathologist. A total of 258 patients were subsequently treated with interferon monotherapy. There was a significant difference in the prevalence of ANA (1:40) by geographic location: Lund 4.4%, London 8.7%, Padova 10.3% [odds ratio (OR) = 0.66; 95% CI: 0.46-0.94; P = 0.023]. Duration of HCV infection, age at infection, current age, route of infection, viral genotype, alcohol consumption, fibrosis stage and inflammatory score were not correlated with ANA+ or ANA pattern. Female gender was correlated with ANA+ and this association persisted in multivariable analyses (OR = 3.0; P = 0.002). Increased plasma cells were observed in the liver biopsies of ANA-positive individuals compared with ANA-negative individuals, while a trend towards decreased lymphoid aggregates was observed [hazard ratio (HR) = 9.0, P = 0.037; HR = 0.291, P = 0.118, respectively]. No correlations were observed between ANA positivity and nonresponse to therapy (OR = 1.4; P = 0.513), although ANA+ was correlated with faster rates of liver fibrosis, this was not statistically significant (OR = 1.8; P = 0.1452). Low titre ANA+ should not be a contraindication for interferon treatment. Our observation of increased plasma cells in ANA+ biopsies might suggest B-cell polyclonal activity with a secondary clinical manifestation of increased serum immunoglobulins.
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK. ylee@edc.pitt.edu
authors.forename: L J
authors.initials: LJ
authors.lastname: Yee
authors.forename: P
authors.initials: P
authors.lastname: Kelleher
authors.forename: R D
authors.initials: RD
authors.lastname: Goldin
authors.forename: S
authors.initials: S
authors.lastname: Marshall
authors.forename: H C
authors.initials: HC
authors.lastname: Thomas
authors.forename: A
authors.initials: A
authors.lastname: Alberti
authors.forename: M
authors.initials: M
authors.lastname: Chiaramonte
authors.forename: J-H
authors.initials: JH
authors.lastname: Braconier
authors.forename: A J
authors.initials: AJ
authors.lastname: Hall
authors.forename: M R
authors.initials: MR
authors.lastname: Thursz
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use; D015551:Autoimmunity; D001706:Biopsy; D002460:Cell Line; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008099:Liver; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012727:Sex Characteristics
chemical_list: D000974:Antibodies, Antinuclear; D000998:Antiviral Agents; D007372:Interferons