autoantibodies (anti-nuclear [ANA], 10 anti-smooth muscle To investigate the factors that may confer susceptibil-
[SMA], 11 anti-GOR, 12 anti-liver, kidney microsomes [LKM] ity or protection to hepatitis C virus (HCV) infection and antibodies 13 ). Despite these observations, however, it reto HCV-associated immunological disorders, we demains to be established by controlled epidemiological studies signed two studies on 420 Sardinian transfusion-depenwhether these immunological abnormalities are more fredent thalassemia patients followed in our department in quent in patients with chronic HCV infection than in normal Cagliari since 1974. The first one was an epidemiological subjects. 14 While the HCV-associated immunological disorsurvey aimed to evaluate the prevalence of HCV infecders seem to be independent on HCV serotype, 15 a possible tion and HCV-associated immunological disorders. In relationship between HCV and host factors involved in the the second study, the distribution of different HLA class immune response, such as the antigens encoded by the HLA II genes was examined by DNA analysis in 116 HCV positive patients, 30 HCV negative patients, and 606 healthy class II region, has not been clearly established. 14
controls. Three hundred fourteen patients became in-
The large cohort of transfusion-dependent thalassemia pafected with HCV (74.7%) after 5.6 { 2.8 years of regular tients followed in our department from the first year of life transfusion program. Mixed cryoglobulinemia, purpura, provided us with a good model for studying these aspects, arthritis, proteinuria, decreased complement levels, because most of them were infected by HCV and have develrheumatoid factor and anti-GOR, smooth muscle antioped chronic hepatitis, 16,17 whereas the remaining were not, body (SMA), anti-nuclear antibody (ANA), and liver, kiddespite the same transfusion risk. Furthermore, the involveney microsome (LKM) autoantibodies were significantly ment of host dependent factors may be more easily explored more represented in HCV positive patients than in negain view of the genetic homogeneity of the Sardinian populative ones (P รต .05). A significant increase of HLA class tion. This is confirmed by the similar distribution of the vari-II DR2 subtype (DRB1*1601,DQB1*0502) was observed ous HLA class genes in all the districts of the Island 18,19 and in a group of 30 HCV negative patients who despite 10.3 the observation that 96% of 3,000 Sardinian b-thalassemics { 2.2 years in a regular blood transfusion program did have the same mutation at codon 39 of the b-globin gene. 20 not show any evidence of HCV infection (Pc รต .0092).
In light of these considerations we devised two complemen-Our results represent clear evidence for a relationship tary studies. The first was an epidemiological survey to evalubetween HCV infection and immune extrahepatic abnorate the prevalence of clinical, biochemical, and immunologimalities. A gene(s) located in the human major histocomcal HCV-associated abnormalities in a group of 420 patibility complex (MHC) region may play an important transfusion-dependent thalassemia patients. In the second role in conferring protection against HCV infection. one, after dividing the patients into different cohorts on the (HEPATOLOGY 1996;24:1338-1341.)
basis of the first study, we were able to investigate the pathogenesis of host dependent factors linked to the HLA class II region. Hepatitis C virus (HCV) is the major cause of transfusion and community-acquired non-A, non-B hepatitis. This infection becomes chronic in approximately 90% of the cases, sugstandard procedures. Iron chelation therapy was performed with daily subcutaneous administration of desferrioxamine (40 mg/kg/ day). All patients received hepatitis B virus vaccination. We excluded Abbreviations: HCV, hepatitis C virus; ANA, anti-nuclear antibody; SMA, smooth muscle from our study 26 immunodeficiency virus-1 seropositive patients, 4 antibody; LKM, liver, kidney microsome; MC, mixed cryoglobulinemia; IgG, immunoglobuwith diseases that could in principle induce secondary cryoglobulilin G. nemia (i.e., cancer, lymphoma, other bacterial or viral infections) and From