Epidemiology and clinical importance of GB virus C/hepatitis G virus

University dissertation from Stockholm : Karolinska Institutet, Department of Immunology, Microbiology, Pathology and Infectious Diseases

Abstract: GB virus C (GBV-C) or hepatitis G virus (HGV) is a recently discovered enveloped RNA virus belonging to the Flaviviridae family. GBV-C/HGV has been suggested to be a causative agent of non-A-non-E hepatitis. However, several contradictory observations cast doubts that it actually causes hepatitis. The aim of this thesis was to further characterize the epidemiology and clinical importance of GBV-C/HGV infections. We developed an in-house GBV-C/HGV RT-PCR. Serum samples from persons with or without risk for parenteral exposure were analyzed for the presence of GBV-C/HGV RNA. Detection of GBV-C/HGV RNA was found to be associated with risk factors for blood-borne infections indicating a blood-borne transmission. We found a prevalence (3%) of GBV-C/HGV viremia among healthy adult volunteers and similar prevalence rates among children. Sequence analysis of amplified GBV-C/HGV fragments from two GBV-C/HGV RNA positive children and their mothers indicated vertical/perinatal transmission. The transmission of GBV-C/HGV was further studied up to three generations in three families. We found intra-familial transmission but no evidence for GBV-C/HGV transmission over more than two generations. The clinical impact of GBV-C/HGV infection was studied in different groups of patients and in healthy individuals. No difference in the prevalence of GBV-C/HGV infection was seen in children with versus children without liver disease. We found a higher frequency of GBV-C/HGV markers among patients with fulminant hepatic failure (FHF) as compared to healthy volunteers. The relation between GBV-C/HGV markers and FHF, however, was in many cases most likely accidental and secondary to treatment with contaminated blood/blood products. 37/1254 (3%) Swedish blood donors negative for HBV, HCV and HIV markers were found GBV-C/HGV RNA positive. Thirty-three of them were clinically examined and from 17 a liver biopsy was performed. None of these donors had clinical evidence of liver disease and all had normal liver biochemistry. No donor evaluated had signs of inflammation or fibrosis in their livers. Two biopsies showed marked steatosis, both donors, however, carried a substantial overweight offering an explanation for these findings. Thus, GBV-C/HGV infection does not seem to Cause liver disease in Swedish blood donors. To clarify the putative liver tropism of GBV-C/HGV, in-house methods to detect GBV-C/HGV RNA by in situ hybridization and E2 protein by immunohistofluorescence in liver tissue sections was developed. By using these techniques, gene and/or protein expression in the cytoplasm of hepatocytes was found in 10 of 15 tested donors positive for GBV-C/HGV RNA in serum. Our data show that GBV-C/HGV infection is common in children and adults. Infection by GBV-C/HGV may occur through contaminated blood/blood products, intravenous drug use, vertically/perinatally from mother to child, sexually, and possibly through close social contacts. Our data do not support the notion that GBV-C/HGV infection is a common cause of hepatitis, In fact, blood donors with GBV-C/HGV single infection do not show clinical, biochemical or histological signs of liver disease despite that GBV-C/HGV may infect and replicate in hepatocytes. Thus, at present no firm evidence exist that GBV-C/HGV is a common cause of hepatitis. It cannot, however, be excluded that GBV-C/HGV may cause liver disease or other diseases under certain circumstances.

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