title: Increased incidence of anti-cardiolipin antibodies in patients with hepatitis C is not associated with aetiopathogenetic link to anti-phospholipid syndrome.
abstract: OBJECTIVE
  Chronic infection with hepatitis C virus (HCV) has been found to be associated with various diseases known as extra-hepatic manifestations of HCV. Recently, HCV has been implicated as a cause of the antiphospholipid syndrome (APLS). We conducted a study in a well-characterized area for epidemiological and prospective studies in the north-western part of Greece in order to address whether an aetiopathogenesis exists between HCV and APLS.
  
  
  METHODS
  Seventy-five patients with chronic hepatitis C were investigated for the presence of anti-cardiolipin antibodies (anti-CL) and for a past medical history supportive to the diagnosis of APLS. In addition, 24 patients with well-defined APLS (primary or secondary) and 12 patients with systemic lupus erythematosus (SLE) were tested for the presence of markers of HCV infection (anti-HCV and HCV RNA). The SLE patients were anti-CL-positive but none of them had developed any of the known clinical features of APLS. In addition, 267 healthy subjects were investigated for the presence of anti-CL.
  
  
  METHODS
  IgG and IgM anti-CL were determined by a quantitative isotype-specific solid phase enzyme-linked immunosorbent assay set up in our laboratory. Anti-HCV was determined using a third-generation enzyme immunoassay and a confirmatory third-generation recombinant immunoblot assay. Active virus replication was defined by the detection of HCV RNA using a combination assay based on a reverse transcriptase polymerase chain reaction and a DNA enzyme immunoassay.
  
  
  RESULTS
  Of the HCV patients, 37.3% had IgG and/or IgM anti-CL (P<0.00005 compared to healthy controls (2.25%)). However, the mean titres of each specific isotype were significantly lower in HCV patients compared with those found in the APLS patients (P<0.05 for IgM and P<0.001 for IgG isotypes). The mean titres of IgG anti-CL were also significantly lower in HCV patients compared with those found in the SLE patients (P<0.01). All patients with APLS or SLE (n = 36) tested negative for HCV infection markers. In addition, neither thrombotic events nor thrombocytopenia were associated with a positive anti-CL test in HCV patients.
  
  
  CONCLUSIONS
  A significant proportion of HCV patients (37.3%) had detectable anti-CL of low titre. However, this finding was not associated with the development of APLS. On the other hand, none of the APLS patients was positive for HCV. Taken together, our data rather failed to reveal an aetiopathogenetic link between HCV and APLS. For this reason, testing for HCV in patients with APLS or follow-up for the possibility of the development of APLS in HCV patients cannot be suggested, at least in Greek patients. More prospective studies of longer duration are required in order to address whether HCV is involved or not in the aetiopathogenesis of APLS.
authors.affiliation: Larisa Medical School, University of Thessaly, Greece. dalekos@med.uth.gr
authors.forename: G N
authors.initials: GN
authors.lastname: Dalekos
authors.forename: K G
authors.initials: KG
authors.lastname: Kistis
authors.forename: D S
authors.initials: DS
authors.lastname: Boumba
authors.forename: P
authors.initials: P
authors.lastname: Voulgari
authors.forename: E K
authors.initials: EK
authors.lastname: Zervou
authors.forename: A A
authors.initials: AA
authors.lastname: Drosos
authors.forename: E V
authors.initials: EV
authors.lastname: Tsianos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017153:Antibodies, Anticardiolipin / Q000097:blood*; D016736:Antiphospholipid Syndrome / Q000453:epidemiology / Q000821:virology*; D016022:Case-Control Studies; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006115:Greece / Q000453:epidemiology; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D018937:Hepatitis C Antibodies / Q000032:analysis; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D015994:Incidence; D008180:Lupus Erythematosus, Systemic / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017153:Antibodies, Anticardiolipin; D018937:Hepatitis C Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012367:RNA, Viral