Extrahepatic immunological manifestations of hepatitis C virus in dialysispatients

Background. Hepatitis C virus (HCN) infection may be associated with variou s extrahepatic immunological disorders. Uremic patients on chronic regular dialytic treatment (RDT) frequently develop immunological abnormalities. Th e aim of this study was to evaluate the probability that HCV infection crea tes an increased risk for extrahepatic immunological abnormalities in chron ic RDT patients. Subjects and Methods. In a series of one hundred sixteen chronic RDT patien ts, HCV status was determined by anti-HCV antibodies, polymerase chain reac tion (PCR) RNA and viral genotyping. After excluding four anti-HCV negative /PCR-RNA positive patients, a comparison was made between 51 anti-HCV negat ive/PCR-RNA negative and 61 anti-HCV positive patients, this latter group i ncluding seventeen PCR-RNA negative, fifteen genotype 1, thirteen genotype 2, three genotype 3, four genotype 4, four undeterminable genotype and five mixed genotypes. The following investigations were performed: cryoglobulin emia (presence, titer and, when possible, identification), monoclonal gammo pathy, antineutrophil cytoplasm antibodies, antidouble stranded DNA antibod ies, circulating immunocomplexes and immunoglobulin levels. Results. Cryoglobulinemia was found in 77% of anti-HICV positive versus 29% of anti-HCV negative patients, and cryocrit > 1% in 50% versus 9.8% respec tively, p =< 0.01. Also cryoglobulin concentration was higher (logarithmic transformation: 4.38+/-0.94 vs 3.11+/-1.06, p =< 0.001) in anti-HCV positiv e versus negative patients. Multivariate logistic regression analysis showe d a significantly increased odds ratio (12.0, confidence interval 3.0 to 48 .3) for having high levels of cryoglobulins (cryocrit >1%) after adjusting for age and dialytic age. The prevalence of this abnormality did not differ significantly among patients infected with different genotypes, but a tend ency towards a lower frequency was observed in the anti-HCV positive/PCR ne gative subgroup. Cryoglobulins were identified as type I (2 anti-HCV positi ve case), type II (2 anti-HCN positive and I anti-HCN negative case) and ty pe 3 (1 anti-HCV negative case). The frequency of monoclonal gammopathy was not significantly different between anti-HCV positive and anti-HCV negativ e patients (6,5% versus 2%) as well as that of the other parameters evaluat ed except for Ige concentration which was higher in the anti-HCV positive g roup (1685+/-605 versus 1349+/-352 mg/dl, p 0.006). Five events, potentiall y linked to HCN infection, occurred in our anti-HCN positive patients: 2 ca ses of porphyria cutanea, 1 case of unexplained peripheral neuropathy, 1 cu taneous leukocytoclastic vasculitis, 1 death for non-Hodgkin's lymphoma. In one anti-HCN positive patient treated with interferon-cr, the presence of cryoglobulins, monoclonal gammopathy and high IgG levels strictly parallele d that of viremia, disappearing during the recovery phase under treatment a nd reappearing shortly after stopping treatment. Conclusions. HCV infection provides a significantly increased risk for deve loping extrahepatic immunological abnormalities also in chronic RDT patient s. It is possible that the clinical relevance of this event might be scant because of the low level of these abnormalities, but an awareness of its po ssibility should to be taken into account.