Prevalence of GBV C/HGV RNA and GBV C/HGV antibodies in French volunteer blood donors: results of a collaborative study.

BACKGROUND AND OBJECTIVES: Posttransfusion hepatitis still occurs at an incidence of about 1 in 118,000 for HBV and 1 in 220,000 for HCV. This collaborative study aimed to determine the prevalence of a novel flavivirus, GBV-C/HGV, even though its role in transfusion-associated hepatitis is uncertain. MATERIALS AND METHODS: GBV-C/HGV RNA was detected by PCR using either the Boehringer detection kit or by primers previously described. HGV antibodies were detected by a serological assay from Boehringer. RESULTS: The observed GBV-C/HGV RNA frequency was 3.4%. HGV antibodies occurred in 9.5% of donors. CONCLUSION: In our study, 12. 9% of the donors had been in contact with the GBV-C/HGV virus.

GEMHEP multicenter quality control study of PCR detection of GB virus C/hepatitis G virus RNA in serum.

PCR is, to date, the only available tool for the detection of GB virus C (GBV-C) and hepatitis G virus (HGV) RNAs. Twenty-two French laboratories participated in a quality control study to assess the sensitivity and specificity of their procedures. The panel included 13 positive controls and 7 negative controls. The laboratories used either in-house PCR techniques adapted from the literature or partly standardized commercial tests. Three laboratories performed faultlessly with the entire panel. Most laboratories had excellent specificity (100% in 20 of 22 laboratories). Sensitivity was acceptable (85 to 100%) in 15 centers and insufficient (38 to 77%) in 7. As with nonstandardized in-house PCR, the commercial assays gave discrepant performances in different laboratories. These results suggest that laboratories willing to use PCR for detection of GBV-C/HGV RNA for research or diagnostic purposes should participate in multicenter quality control trials.

Natural history of GBV-C/hepatitis G virus infection through the follow-up of GBV-C/hepatitis G virus-infected blood donors and recipients studied by RNA polymerase chain reaction and anti-E2 serology.

The aims of this study were to determine the outcome and the natural history of GBV-C/hepatitis G virus (HGV) infection and to establish the frequency of acute or persistent infections in multiply-transfused individuals and blood donors. We used a GBV-C/HGV RNA polymerase chain reaction (PCR) and an assay evidencing antibodies to the envelop protein E2, which is considered a marker for virus clearance. Among 16 PCR-positive recipients, 11 were still positive for GBV-C/HGV RNA at the end of the study period; six of the 16 recipients were GBV-C/HGV infected during the study period and thus had a well-defined date of infection. The 16 patients were shown to carry GBV-C/HGV RNA over a mean period of 4.4 years, for a mean observational period (defined as the follow-up period since the first sample positive for GBV-C/HGV RNA) of 5.3 years. Within the limits of the study period, the patients with a well-defined date of infection were positive for GBV-C/HGV RNA during a mean period of 4.7 years. If defined by the presence of GBV-C/HGV RNA for at least 6 months, the persistent infection rate was 100% in this recipient cohort. Serum anti-E2 antibody was evidenced at least once in five (31.2%) recipients and, except in one case, became detectable after the loss of GBV-C/HGV RNA. Among the 11 blood donors, all were still positive for GBV-C/HGV RNA after a mean follow-up period of 7.7 months. The persistent infection rate was 100% in this donor cohort. Once acquired, the infection to GBV-C/HGV generally tends to persist in immunocompetent patients.

Prevalence of hepatitis G virus RNA in French blood donors and recipients.

BACKGROUND: Recently, cases of chronic hepatitis were linked to the presence of genomic sequences of a newly described RNA virus termed hepatitis G virus (HGV) and belonging to the Flaviviridae family. STUDY DESIGN AND METHODS: The presence of HGV RNA was searched for by polymerase chain reaction in a population of blood donors and in patients who had received multiple blood component transfusions and/or intravenous immunoglobulin (IVIG) infusions. RESULTS: Twenty-one (4.2%) of 500 donors were positive for HGV RNA as were 21 (10.7%) of 196 nonimmunosuppressed patients who had received multiple transfusions of packed red cells, 4 (8.7%) of 46 common variable immune deficiency (CVID) patients who had received only IVIG, and 22 (24.7%) of 89 bone marrow transplant (BMT) patients who had received IVIG and cellular components. The proportion of HGV-positive individuals was significantly higher in the immunosuppressed recipients (CVID and BMT patients) than in the nonimmunosuppressed patients who were multiply transfused with packed red cells (p < 0.03). The proportion of HGV-positive individuals was significantly higher in the BMT patients who had received IVIG and cellular components than in the CVID patients who had received IVIG only (p < 0.03). Eight (17.0%) of the 47 HGV-positive recipients and 48 (16.9%) of the 284 HGV-negative recipients had a serum alanine aminotransferase level higher than the upper limit of normal (nonsignificant difference). The medical history of HGV-positive donors failed to reveal a particular at-risk event. The large majority of HGV-infected patients had a normal serum alanine aminotransferase level, and the proportion of patients with elevated alanine aminotransferase was the same in HGV-positive and in HGV-negative recipients. CONCLUSION: The pathological significance of HGV infection remains unelucidated, and the classification of HGV as a new hepatitis virus was perhaps premature.

Prevalence and clinical features of hepatitis G virus infection in bone marrow allograft recipients.

To study the prevalence and clinical features of hepatitis G virus (HGV)/GB virus C (GBV-C) infection in bone marrow transplantation (BMT), we examined frozen serum samples from 95 bone marrow allograft patients for HGV/GBV-C RNA by RT-PCR. Twenty-eight out of 95 (29.5%) were positive and 14 of the HGV+ patients were already positive before transplantation. The mean numbers of blood donors to whom the HGV and HGV+ populations were exposed before BMT were not significantly different (Kruskal-Wallis test, P = 0.08, NS) but did reveal that the HGV+ population had been transfused more often. Moreover, all but one of the patients who were HGV+ before graft, had had hematological diseases which needed heavy transfusion protocols suggesting, a role of blood products in HGV transmission. Fifty out of the 95 patients received Gammagard intravenous immunoglobulin (i.v.IG) batches suspected of having transmitted HCV. However, no significant difference appeared between these recipients and those receiving other i.v.IG. Despite their immunodeficiency, no clinical or biological evidence of liver disease potentially linked to HGV infection has as yet been observed. The clinical outcome, in terms of acute GVHD, chronic GVHD or veno-occlusive disease was similar in HGV+ and HGV- recipients suggesting the absence of adverse effects of HGV infection on the early outcome of allogenic BMT. Long-term evolution remains to be prospectively studied.

Transmission of hepatitis C virus in allografted patients: use of viral genotyping as an epidemiological marker.

One hundred and ninety-two allografted patients were tested for hepatitis C virus (HCV) RNA from 1992 to 1995 in Saint-Louis Hospital (Paris). They received blood products and intravenous immunoglobulins (IVIG) and more particularly Gammagard IVIG suspected of transmitting HCV (batches distributed in France between January 1993 and February 1994). The presence of serum HCV RNA was tested by polymerase chain reaction (PCR) in 86 patients who received Gammagard IVIG during the critical period and in 106 patients treated with IVIG other than the suspected batches of Gammagard (negative controls). HCV RNA positive sera were HCV genotyped. Ten out of 86 patients who received Gammagard IVIG during the exposed period vs 0 out of 106 negative controls were HCV RNA positive showing a higher prevalence of HCV infection in the exposed patients that in the negative controls (P = 0.001). The link between HCV transmission and IVIG infusion was reinforced by the high frequency of genotype 2b (70%) in the exposed patients because genotype 2b is an underrepresented subtype in France (< 1%).

Infection by hepatitis C virus through contaminated intravenous immune globulin: results of a prospective national inquiry in France.

BACKGROUND: A recent hepatitis C virus (HCV) outbreak has been suspected of being caused by an infusion of intravenous immune globulin. STUDY DESIGN AND METHODS: Three laboratories were mandated by the French regulatory agency to prospectively screen on a national scale those persons having received suspected batches: 233 exposed patients were recalled and tested for HCV antibody and for HCV RNA. RESULTS: Nineteen patients (8.1%) were found positive for HCV RNA; 7 of these 19 were positive for the HCV antibody. CONCLUSION: The link between HCV infection and intravenous immune globulin was reinforced by the overrepresentation of the 2b genotype (58%), which contrasts with the low prevalence of this genotype in France (1%).