title: Clinical impact of non-organ-specific autoantibodies on the response to combined antiviral treatment in patients with hepatitis C.
abstract: BACKGROUND
  Hepatitis C virus (HCV)-related chronic hepatitis is frequently associated with non-organ-specific autoantibodies (NOSAs), but available data about the relationship between NOSA positivity and the effect of antiviral therapy in persons with hepatitis C are few and controversial. Our aim was to evaluate the impact of NOSA positivity on the outcome of combined antiviral therapy in HCV-positive patients.
  
  
  METHODS
  A total of 143 consecutive adult patients with hepatitis C were studied. Antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), and anti-liver/kidney microsomal antibody type 1 (LKM1) were detected by indirect immunofluorescence. All patients were treatment naive and received combined antiviral therapy (interferon [IFN]-ribavirin) after enrollment in the study. Patients were classified as nonresponders if HCV RNA was detectable after 6 months of therapy, as relapsers if abnormal transaminase levels and reactivation of HCV replication were observed after the end of treatment, and as long-term responders if transaminase levels were persistently normal and HCV RNA was undetectable 6 months after the end of treatment.
  
  
  RESULTS
  Thirty-seven patients (25%) were NOSA positive (SMA was detected in 19 patients, ANA in 10, ANA and SMA in 4, LKM1 in 3, and SMA and LKM1 in 1). The prevalence of long-term response was similar between NOSA-positive patients and NOSA-negative patients (48.6% vs. 56.6%; P=not significant). Compared with HCV genotype 1 (HCV-1), HCV genotypes other than 1 were more often associated with long-term response among NOSA-positive patients (93.3% vs. 30%; P=.0017). The overall rate of long-term response, irrespective of NOSA status, was 54.5%. Detection of HCV-1 and elevated gamma-glutamyl transpeptidase serum levels were independent negative prognostic factors of treatment response (P=.007 and P=.026, respectively).
  
  
  CONCLUSIONS
  Combined antiviral treatment (IFN-ribavirin) is safe and effective in NOSA-positive patients with hepatitis C, even if long-term response is less likely in those infected with HCV-1.
authors.affiliation: Department of Internal Medicine, Cardioangiology, Alma Mater Studiorum-University of Bologna, Policlinico Sant'Orsola-Malpighi, Bologna, Italy. paolomuratori@tin.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Muratori
authors.forename: Luigi
authors.initials: L
authors.lastname: Muratori
authors.forename: Marcello
authors.initials: M
authors.lastname: Guidi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Granito
authors.forename: Micaela
authors.initials: M
authors.lastname: Susca
authors.forename: Marco
authors.initials: M
authors.lastname: Lenzi
authors.forename: Francesco B
authors.initials: FB
authors.lastname: Bianchi
mesh_terms: D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000276:immunology; D000918:Antibody Specificity; D000998:Antiviral Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D009130:Muscle, Smooth / Q000276:immunology; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000974:Antibodies, Antinuclear; D000998:Antiviral Agents; D001323:Autoantibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; C060729:anti-liver kidney microsome antibody; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b