Human pegivirus (HPgV) (formerly known as GBV-C)

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Record number: 
Adverse Occurrence type: 
MPHO Type: 
Estimated frequency: 
It is estimated that one-sixth of the world population is seropositive for GB virus type C (GBV-C), now called Human pegivirus (HPgV-1), and approximately 750 million individuals worldwide have had viremia. The prevalence of GBV-C viremia is 1-5% among healthy blood donors from developed countries, but is much higher in developing countries. The pooled prevalence rates vary with rates of 1.7% in North America, 2.3% in Europe, 2.4% in Asia, and 9.1% in South America. Reported rates of viremia are higher in individuals with hepatitis C virus (HCV) 11-24% and HIV 42%. In the United states approximately 2% of healthy donors have GBV-C viremia, and 13% have the E2 antibody, which indicates prior infection. Transmission is associated with lower human immunodeficiency virus (HIV) load and slower HIV disease progression. Because of the routes of transmission which include sexual, parenteral, and vertical routes, this infection is more prevalent among HIV infected individuals and HCV infected individuals. Some studies have shown prolonged survival slower disease progression and lower mortality among HIV-infected individuals who have GBV-C infection. The most notable protective effect is in those individuals who become infected with GBV-C five to six years after HIV seroconversion. The prolonged HIV survival may be due to GBV-C interference with HIV replication, modulation of HIV entry receptors, alteration of T helper cell 1 and T helper cell 2 cytokine profiles, decreased T cell activation, and blockage of interleukin 2 mediated CD4 T cell proliferation. Coinfection with GBV-C does not appear to impact the clinical course of outcomes of HCV infection. In patients with HIV/HCV coinfection, GBV-C viremia has been associated with a significant reduction in HCV-related liver morbidity.
Time to detection: 
Detection of GBV-C RNA is performed by polymerase chain reaction (PCR). The sensitivity and specificity of this test are unknown and the true incidence of infection may be underestimated. Few studies describe predictors of acute GBV-C infection following transfusion in HIV-infected patients. In this study GBV-C RNA was detected in 7.5% of subjects within 120 days following the first transfusion. With each transfused unit, the risk increased. Transmission of GBV-C by blood transfusion was inversely related to HIV load.
Alerting signals, symptoms, evidence of occurrence: 
It was initially thought to cause hepatitis in humans, but several studies have failed to demonstrate an association between GBV-C infection and any human disease. It is not transmitted by leukoreduced blood products. Immunocompetent individuals infected with GBV-C usually spontaneously clear the viremia within 2 years.
Demonstration of imputability or root cause: 
The study retrospectively evaluated pre- and post-transfusion blood specimens for evidence of GBV-C infection, and finds an association between transfusion and GBV-C acquisition, although currently this is an association and requires further study to determine if there is true transfusion-transmission. There has been no association between GBV-C infection and any human disease. Blood products are not routinely screened for the presence of GBV-C RNA. Infection typically lasts for >6 months and is cleared spontaneously in more than 50 percent of infections within two years. Appearance of antibodies to the major viral envelope glycoprotein (E2) are thought to be associated with the clearance of viremia. There has been a protective association noted between GBV-C viremia and HIV and HIV/HCV patients.
Imputability grade: 
Not Assessable
Suggest new keywords: 
HIV infection
HCV infection
Suggest references: 
- Transmission of GB virus type C via transfusion in a cohort of HIV-infected patients. Vahidnia F et al. J Infect Dis. 205(9):1436-42, 2012 May 1. - Stapleton JT, Foung S, Muerhoff AS, Bukh J, Simmonds P. The GB viruses: a review and proposed classification of GBV-A, GBV-C (HGV), and GBV-D in genus Pegivirus within the family Flaviviridae. J Gen Virol. 2011 Feb;92(Pt 2):233-46. doi: 10.1099/vir.0.027490-0. Epub 2010 Nov 17. PMID: 21084497; PMCID: PMC3081076. - Bhattarai N, Stapleton JT. GB virus C: the good boy virus? Trends Microbiol. 2012 Mar;20(3):124-30. doi: 10.1016/j.tim.2012.01.004. Epub 2012 Feb 8. PMID: 22325031; PMCID: PMC3477489.
MG to Second Reviewer: I'm very interested in you carefully considering the imputability evidence please, in addition to anything else you wish to add. I'm a little confused with what to do with imputability - mixture of whether the acquisition of the virus is truly an "adverse event" is part of it, and also I'm not feeling entirely clear about the quality of the data re: transfusion transmission of the agent - the authors stated "Our study provides evidence of high rates of GBV-C transmission by transfusion in HIV-infected subjects, as well as an increased odds of GBV-C acquisition with lower pre- transfusion HIV load and current use of HAART, after control for the cumulative numbers of units of blood transfused." what do you think of the quality of the study and its data - is the imputabilty score really zero b/c of the study, or is it linked to the question of whether that is an AE? (I think I agree with the reviewer on that call, but would feel better with another expert opinion on this). There is little interest in the virus since 2012 in the medical literature, so there is probably not much else to add other than "it has been investigated for transfusion-transmission, (??) it may be TT (at least among HIV-infected individuals), but there remains no evidence of human disease caused by the virus. (at least this is what I the believe is the case, and will appreciate any clarifications in the record above according to your expertise, if needed)
Expert comments for publication: 
GBV-C which is a human flavivirus that is phylogenetically related to the hepatitis C virus is mainly a lymphotropic virus that replicates in T and B lymphocytes. It is not transmitted by leukoreduced blood products. Immunocompetent individuals infected with GBV-C usually spontaneously clear the viremia within 2 years. The E2 antibody usually appears after viremia clearance and could possibly provide protection from reinfection. The E2 antibody response is variable and has been seen to wane therefore, it is difficult to accurately interpret E2 antibody levels. Both E2 antibody levels and GBV-C RNA levels can be detected in tandem. GBV-C RNA levels indicate active infection. In this study, GBV-C RNA was detected in 22 (7.5%) of 294 HIV-infected patients who were GBV-C negative before transfusion of non-leukoreduced RBCs. As testing of donor samples and donor-recipient matching was not performed, the results indicate that the acquisition of the virus through transfusion to HIV-infected patients is possible. Several studies, including this, have failed to demonstrate an association between GVB-C viraemia and any human disease. Thus, this occurrence does not involve actual harm for which the imputability score is not applicable.