title: Hepatitis B virus replication in damaged endothelial tissues of patients with extrahepatic disease.
abstract: Hepatitis B virus (HBV) infection may be complicated by extrahepatic manifestations such as polyarteritis nodosa (PAN), glomerulonephritis, polymyositis, and dermatitis, but the etiology of these processes is not yet clear. HBV replication has been demonstrated in a variety of extrahepatic tissues and cell types, but the possible pathogenetic role of extrahepatic HBV replication has not been fully explored in patients with extrahepatic manifestations of HBV infection. In this case series, immunohistochemistry and in situ hybridization studies were performed on extrahepatic tissues from one HBsAg-positive patient with PAN and another HBsAg-positive patient with polymyositis, using HBsAg-seronegative control subjects with the same vasculitic disorders as controls. Tissue samples from the two study patients had detectable HBV RNA, replicative intermediates of HBV DNA, as well as HBsAg and HBcAg localized to vascular endothelium. In contrast, HBsAg-negative control patients had no tissue reactivity. Our results suggest that patients with HBV-related extrahepatic disease have evidence of viral replication in damaged extrahepatic endothelial tissues. While further studies would be required to support a hypothesis of causality, these findings suggest a role for both immune complex deposition and viral replication within diseased endothelial tissue in the pathogenesis of these poorly understood extrahepatic disorders.
authors.affiliation: Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mason
authors.forename: Jeremy
authors.initials: J
authors.lastname: Theal
authors.forename: Vince
authors.initials: V
authors.lastname: Bain
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Adams
authors.forename: Robert
authors.initials: R
authors.lastname: Perrillo
mesh_terms: D000328:Adult; D004279:DNA, Viral / Q000235:genetics; D004730:Endothelium, Vascular / Q000473:pathology / Q000821:virology*; D005260:Female; D006509:Hepatitis B / Q000473:pathology / Q000821:virology*; D006512:Hepatitis B Core Antigens / Q000032:analysis; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007105:Immune Complex Diseases / Q000473:pathology / Q000821:virology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000473:pathology / Q000821:virology; D010488:Polyarteritis Nodosa / Q000473:pathology / Q000821:virology*; D017285:Polymyositis / Q000473:pathology / Q000821:virology*; D012367:RNA, Viral / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D014764:Viral Proteins / Q000032:analysis / Q000235:genetics; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D012367:RNA, Viral; D014764:Viral Proteins