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    • Heavy alcohol consumption reported by three of five referred

    2022-05-10

    Heavy alcohol consumption, reported by three of five referred patients with chronic HCV infection and cirrhosis, is a risk factor for cirrhosis in p.C282Y homozygotes [19], [47] and adults with chronic HCV infection [48]. Although none of the present referred patients were diagnosed to have porphyria cutanea tarda, the proportion of HFE p.C282Y homozygotes in US case series of porphyria cutanea tarda is greater than the proportion of p.C282Y homozygotes in the general US A-54556A [49], [50]. Among p.C282Y homozygotes with porphyria cutanea tarda, liver injury is greatest in those who also have chronic HCV infection and heavy alcohol consumption [50]. One of the present referred patients also had hepatocellular carcinoma, possibly due to interaction of iron overload [34] and chronic HCV infection [51]. The present results and those of a previous report [19] suggest that chronic HCV infection contributes less than iron overload and heavy alcohol consumption to overall cirrhosis risk in p.C282Y homozygotes in North America because the prevalence of HCV infection in this region is low. Limitations of the present study include lack of hepatitis C RNA analyses and liver biopsies in post-screening participants with anti-HCV because obtaining these studies was beyond the scope of the HEIRS Study. Liver biopsy specimens were unavailable in two referred HFE p.C282Y homozygotes with chronic HCV infection. It is possible that some HEIRS Study participants and referred patients had occult HCV infection [52], chronic HCV infection with normal ALT levels [53], no HCV infection associated with low levels of anti-HCV [54], or developed chronic HCV infection after diagnosis of hemochromatosis. HEIRS Study participants and some referred patients without elevated ALT levels were not tested for anti-HCV. Among US subjects with HCV infection who were unselected for hemochromatosis, ∼30% have normal ALT levels [55]. This suggests that our estimates of the prevalence of anti-HCV and chronic HCV infection are conservative. Compiling and evaluating other risk factors for chronic HCV infection in adults, including blood transfusion before 1992, lifetime drug use, and lifetime sexual partners [20], were not feasible for referred patients or HEIRS Study post-screening participants. We conclude that the odds ratio of anti-HCV was increased in post-screening participants with elevated SF. Prevalence of anti-HCV in post-screening participants with HFE p.C282Y homozygosity and chronic HCV infection in referred adults with HFE p.C282Y homozygosity in North America is similar to that of Control participants with HFE wt/wt and normal screening TS/SF.
    Funding The HEIRS Study (January 2000–January 2006) was supported by the National Heart, Lung, and Blood Institute, in conjunction with the National Human Genome Research Institute. Individual investigators, grants, and contracts have been acknowledged in detail previously [1], [2]. The present work was supported in part by Southern Iron Disorders Center.
    Author contributions
    Conflict of interest
    Acknowledgments
    Introduction A unique feature of HCV is that both cholesterol metabolism and fatty acid biosynthetic pathways are among the fundamental stones for both RNA replication and virion assembly in host cells [1]. Apolipoprotein E (Apo E), a ligand for low density lipoprotein receptor (LDLr), is now prescribed as an irreplaceable component of the HCV–host lipid interaction through involvement at several stages in the viral lifecycle, including intracellular viral assembly [2], [3]. Apo E has been well described as a main regulator of many steps of lipid (cholesterol and triglyceride) and lipoprotein metabolism, including synthesis and secretion of very low density lipoproteins (VLDL), VLDL hydrolysis to produce low density lipoproteins (LDL) and receptor mediated removal of triglyceride-rich lipoprotein remnants (VLDL and Chylomicrons remnants) by the liver. Lipoviral Particles (LVP) had been identified as low-density HCV virions packaged as LVPs with densities similar to that of the very-low-density lipoprotein (VLDL) and abundance of Apo E on their surface detected by electron microscopy [4], shedding the light on the implication of the Apo E in mediating HCV infectivity via lipoprotein receptors [5]. Furthermore, Apo E have been detected in the low-density fractions of the HCV RNA-containing particles which had been declared as the fractions carries the probability of being infectious [6]. Endocytosis of HCV is mediated by low density lipoprotein receptor (LDLr) and Scavenger receptor B1 (Sc-B1). LDL r normally transports 2 different classes of cholesterol containing lipoprotein particles (LDL & VLDL) which contain multiple copies of Apo E [7]. While Sc-B1 which is expressed primarily in the liver recognizes a broad variety of lipoprotein ligands (HDL, LDL, VLDL and oxidized LDL) [8].