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    • The prevalence of hepatitis C virus HCV infection in

    2022-06-23

    The prevalence of hepatitis C virus (HCV) infection in p.C282Y homozygotes in North America is unknown. We determined the prevalence of anti-HCV antibody and HFE genotype and serum ferritin (SF) associations in non-Hispanic white participants in the Hemochromatosis and Iron Overload Screening (HEIRS) Study who attended a post-screening examination wherein participants with elevated alanine aminotransferase (ALT) levels underwent reflex testing for anti-HCV. We also sought to compare the prevalence and presenting characteristics of chronic HCV infection in two cohorts of referred patients with hemochromatosis and HFE p.C282Y homozygosity in Alabama and Ontario. We compare our prevalence estimates of anti-HCV positivity and chronic HCV infection in p.C282Y homozygotes with those in population cohorts from North America, review observations of the prevalence of p.C282Y homozygosity among patients with chronic HCV infection, and discuss SF levels in patients with HCV infection.
    Methods
    Results
    Discussion The prevalence of combined elevated ALT and anti-HCV in 403 HEIRS Study Control participants with HFE wt/wt and normal screening TS and SF values was 1.0% [95% CI: 0.3, 2.7]. The prevalence of chronic HCV infection in 961 referred non-Hispanic white patients with hemochromatosis and HFE p.C282Y homozygosity in this study was 1.0% [95% CI: 0.5, 2.0]. The prevalence of combined elevated ALT and anti-HCV in 294 HEIRS Study participants with p.C282Y homozygosity was 0.3% [95% CI: 0.02, 2.2]. In a study of 368 p.C282Y homozygotes from US, Canada, and Australia who underwent liver biopsy, one participant (0.3%; [95% CI: 0.01, 2.7]) had HCV infection [19]. These four estimates are consistent with the proportion of 9931 civilian non-institutionalized adult non-Hispanic white participants aged ≥20y in the 2003–2010 National Health and Nutrition Examination Survey who were positive for HCV RNA (1.1% [95% CI: 1.0, 1.4]) [20] and with estimates of HCV infection prevalence in Canada (0.6–0.7%) [21]. The prevalence of chronic HCV infection in Italian patients with iron overload and HFE p.C282Y homozygosity (n=269) or p.C282Y/p.H63D Ertapenem sodium salt heterozygosity (n=69) reported from Milan was 5.9% [22]. The overall prevalence of chronic HCV infection in European countries is highest in Italy (3.0–4.4%) [23]. In central and southern Italy and the major islands of Italy, the prevalence of HCV infection is 12.6–26% [23]. It is likely that the greater prevalence of HCV infection reported in Italian patients with HFE-related hemochromatosis than in US and Canada HFE p.C282Y homozygotes is due in part to the higher general population prevalence of HCV infection in Italy. The present results suggest that susceptibility to anti-HCV positivity or HCV infection or in non-Hispanic white adults with HFE p.C282Y homozygosity in North America is no greater than that of non-Hispanic white adults from US and Canada populations unselected for HFE genotypes or with HFE wt/wt. The prevalence of p.C282Y homozygosity in 100 Massachusetts Caucasian patients with chronic HCV infection did not differ significantly from that of 73 local controls [24] or 2016 non-Hispanic white participants from the Third National Health and Nutrition Examination Survey 1992–1994 [24], [25]. In a study of 246 German patients with chronic HCV infection and 200 control subjects, no participant had p.C282Y homozygosity [26]. In a study of 184 Austrian patients with chronic HCV infection, five patients (2.7% [95% CI: 1.0, 6.6]) were discovered to have HFE p.C282Y homozygosity [27], whereas the prevalence of chronic HCV infection in Austria is <0.5% [28]. Because the numbers of patients in this Austrian hepatitis cohort were relatively small, it is not possible to discern whether the prevalence of chronic hepatitis C in Austrian p.C282Y homozygotes differs significantly from that in the general Austrian population. In a meta-analysis of subjects from diverse geographic areas (mainly case-control studies), the odds ratio for HCV infection in p.C282Y homozygotes vs. subjects without p.C282Y or p.H63D was 4.1 (1.2–14) [29]. Taken together, these observations do not resolve whether p.C282Y homozygotes are more susceptible to developing chronic HCV virus infection than persons with other HFE genotypes, although p.C282Y homozygotes may be more likely to develop hyperferritinemia if they also have chronic HCV infection.