Prevalence of GBV-C/hepatitis G virus RNA and E2 antibody among subjects infected with human immunodeficiency virus type 1 after parenteral or sexual exposure.

GB virus C (GBV-C) or hepatitis G virus (HGV) is transmitted by the parenteral route but the importance of sexual transmission needs to be ascertained. GBV-C/HGV infections were investigated using RNA and E2-antibody detection methods in 80 subjects infected by the human immunodeficiency virus type 1 (HIV-1) divided into 4 groups of 20 individuals each according to their main risk factor for HIV-1 infection: blood product recipients (group 1), intravenous drug users (group 2), homosexuals (group 3), or heterosexual exposure (group 4). The overall prevalence of GBV-C/HGV infection was 66.3%. No significant difference was observed in GBV-C/ HGV prevalence among the four groups: 75, 75, 55, and 60% in groups 1, 2, 3, and 4, respectively. Hepatitis C virus (HCV) antibodies, used as a control for parenteral exposure, were found in 70% and 90% of the subjects in groups 1 and 2 versus only 15% and 20% of the subjects in groups 3 and 4, respectively (P< .001). Similarly, coinfections with GBV-C/HGV and HCV were significantly associated with the parenteral route (P <.001). These data emphasized the usefulness of combining the detection of RNA and the E2 antibody to determine the actual prevalence of GBV-C/HGV infection. The high prevalence of the GBV-C/HGV markers among the HIV-1-infected subjects, especially those with sexual exposure, provides additional evidence that this route of transmission plays a key role in the epidemiology of GBV-C/HGV. The potential influence of GBV-C/HGV infection on the course of HIV-1 disease needs further evaluation.     

Molecular epidemiology of TT virus in Italy and phylogenesis of viral isolates from subjects at different risk for parenteral exposure

The prevalence and genotype distribution of human TT virus (TTV) in Italy were analysed in 593 subjects at different risk of parenteral infection who included blood donors, patients with chronic type C hepatitis (HCV), thalassemic patients, patients on haemodialysis, human immunodeficiency virus type 1 (HIV-1)-negative intravenous drug users (IVDUs), and HIV-1-infected subjects (IVDUs, heterosexual contacts and homosexual males). Plasma TTV-DNA was detected using nested PCR with primers deduced from the N22 region of the open reading frame 1 (ORF-1) and from the untranslated region (UTR) of the viral genome. Phylogenetic analysis of the sequences obtained from ORF-1 was also undertaken. A high prevalence of plasma TTV-DNA was observed using the UTR primers, with rates varying from 83-100% in the study groups. Using the N22 primers, HIV-1 positive IVDUs and homosexual males, haemodialysed patients and thalassemic patients had a significantly higher TTV prevalence (range: 23.0-86.1%) than blood donors, who displayed a high frequency of positivity (10.6%). Sequence analysis of 127 N22-positive isolates revealed that 42.5% were of type 1, 53.5% of type 2, 2.4% of type 3, and that two isolates (1.6%) were closely related to genotypes 1-2 but distinct from the other major genotypes. TTV-2 was significantly more prevalent in patients at high risk for parenteral infection and in HIV-1 positive homosexuals. In sequential samples from 15 TTV-infected subjects, N22 sequences were detectable persistently in 12 (80.0%) and UTR sequences persisted in all 15 patients over a mean period of 29.6 months. This data indicates that TTV is widespread in Italy in parenterally exposed subjects, and that the infection frequently persists.     

GB virus C/hepatitis G virus and TT virus infections among high risk renal transplant recipients in India.

BACKGROUND: GB virus C/hepatitis G virus (GBV-C/HGV) and TT virus (TTV) have been widely reported in patients with high parenteral risk such as haemodialysis and renal transplant recipients. The occurrence of these agents in association with hepatitis B virus (HBV) and hepatitis C virus (HCV), in Indian renal transplant recipients, is yet unreported. STUDY DESIGN: Molecular and serological markers of GBV-C/HGV and TTV were examined in addition to those for HBV, HCV and hepatitis D virus (HDV) in a selected group of seventy renal transplant recipients. HGV RNA detection was achieved using primers specific for the 5'NCR and NS5a regions of the genome. Anti-GBV-C/HGV antibody was detected using the mu plate anti-HG env kit (Roche, Germany). TTV DNA PCR was performed using primers specific for the coding region (method A) of the genome. In 50% of patients, TTV DNA was also tested for using primers specific for the non-coding region (method B). Host related factors such as age, alanine aminotransferase (ALT) levels, number of transfusions, haemodialysis sessions, and months following transplantation were also studied. RESULTS: Exposure rates to GBV-C/HGV, TTV (method A), HBV, HCV and HDV were 58.6, 32.9, 52.9, 54.3 and 2.9%, respectively. 'Active' infection as measured by viraemia and/or virus-specific antigenaemia for GBV-C/HGV, TTV, HBV and HCV was 52.9, 32.9, 15.7 and 52.9%, respectively. The majority of GBV-C/HGV and TTV infections were seen as co-infections with other hepatitis viruses. Single infection with GBV-C/HGV and TTV was seen in ten (14.2%) and eight (11.4%) patients, and was not associated with ALT elevation when compared to uninfected blood donors. Using univariate analysis, GBV-C/HGV RNA was significantly associated with > or =20 haemodialysis sessions. TTV DNA occurrence was not associated with any risk factors. CONCLUSIONS: There is a high occurrence of GBV-C/HGV and TTV in this select group of renal transplant recipients in India. These viruses mostly occurred in the context of co-infections with other hepatitis viruses. Long term effects of multiple hepatotropic viral infections need to be carefully documented in such transplant populations.     

Determination of hepatitis G virus markers in various risk groups

Study of prevalence of hepatitis G virus (HGV) markers in different risk groups showed the presence of HGV RNA in 3.2% blood donors, 24.2% patients with hepatitis C (HCV), and 28% patients with hemophilia. HGV antibodies were detected in 11.3% donors, 16.0% patients with HCV, 13.4% patients with hemophilia, and 8.5% HIV-infected subjects. Anti-E1 HGV were more often detected in the absence of HGV RNA. Antibodies to HGV E2 protein were significantly more often detected in adult HCV patients but not in adolescent patients aged 8-15 years.     

TTV infection and its relation to serum transaminases in apparently healthy blood donors and in patients with clotting disorders who have been investigated previously for hepatitis C virus and GBV-C/HGV infection in Belgium

A novel DNA virus, TT virus (TTV), has been proposed as a possible etiologic agent for non A-E hepatitis. The aim of the present study was to determine the prevalence of TTV infection using PCR in healthy blood donors and in patients with clotting disorders who have been investigated previously for GBV-C/HGV and HCV infection in Belgium. In this study, PCR using primers proposed by Takahashi et al. [(1998) Hepatology Research 12:233-239] proved far more sensitive than those used by Okamoto et al. [(1998) Journal of Medical Virology 56:128-132]. The sequence of the PCR products showed 87% identity to the published sequence. TTV was present in 29.7% of healthy blood donors, a figure intermediate between the low rate of infection observed in Scotland and the high rates in the Far East. TTV was detected in 46.5% of 127 patients studied with clotting disorders as compared to 79.5% for HCV and 11.8% for GBV-C/HGV infection. However, there was no impact on the level of serum transaminases. Treatment with interferon for HCV infection co-infected with TTV suppressed temporarily serum TTV DNA. Therefore, it was concluded that TTV DNA is detected frequently in serum of healthy blood donors in Belgium and more often in patients with clotting disorders. TTV does not cause liver disease or contribute to the severity of liver disease.     

Sexual transmission of GB virus C/hepatitis G virus

Although it is established that infection with GB virus C (GBV-C) or hepatitis G virus (HGV) can be transmitted parenterally, the prevalence of GBV-C/HGV viremia in the general population (2–5%) is relatively high compared with other parenterally borne viruses such as hepatitis C virus. To investigate the possibility of sexual transmission of GBV-C/HGV, we determined the frequency of viremia by the polymerase chain reaction and serological reactivity to the E2 protein by ELISA in samples collected from individuals at risk for sexually transmitted diseases attending a city genitourinary medicine clinic. GBV-C/HGV viremia was detected in 27 of 87 male homosexuals (31%) and 9 of 50 prostitutes (18%), frequencies significantly greater than those in matched controls (2/63) and local blood donors (2.3%). Among nonviremic individuals, a high frequency of serological reactivity to the E2 protein of GBV-C/HGV was also observed in the risk groups (male homosexuals: 14/60; prostitutes: 11/41), although these figures are likely to be underestimates of the frequency of past infection as detectable anti-E2 reactivity may attenuate rapidly over time following resolution of infection. Infection with GBV-C/HGV was more frequent among those coinfected with human immunodeficiency virus type 1. Among male homosexuals from whom retrospective samples were available, evidence for de novo infection was found in 9 of 22 individuals over a mean sampling time of 2.9 years, predicting an annualized incidence of GBV-C/HGV infection of approximately 11% in this group. The high prevalence and incidence of GBV-C/HGV infection in these individuals and prostitutes provides strong evidence for its spread by sexual contact. Further studies are required to investigate the mechanism of its transmission and the clinical significance of acute and persistent infection in these risk groups. J. Med. Virol. 55:203–208, 1998. © 1998 Wiley-Liss, Inc.     

Prevalence of hepatitis B, hepatitis C, GB virus C/hepatitis G and TT viruses in predialysis and hemodialysis patients

Patients with chronic renal failure on hemodialysis have a high risk of infections with viruses such as hepatitis B (HBV), hepatitis C (HCV), GB virus C/hepatitis G (GBV-C/HGV) and TT (TTV) viruses. The prevalence of HBV, HCV, GBV-C/HGV and TTV in patients with chronic renal failure who are on conservative management before entering into a hemodialysis program (predialysis) in comparison with hemodialyzed patients was studied to elucidate whether the high prevalence of these viruses is influenced by that observed in the predialysis stage. The presence of hepatitis B virus surface antigen (HBsAg), HCV RNA, GBV-C/HGV RNA and TTV DNA was analyzed in sera from 80 patients with chronic renal failure (35 on predialysis and 45 on hemodialysis). HBsAg, HCV RNA, GBV-C/HGV RNA and TTV DNA were detected in one (2.8%), six (17.1%), eight (22.5%) and 16 (45.7%) of the 35 patients on predialysis. Two (5.7%) of these patients were coinfected with HCV and GBV-C/HGV, whereas six (17.1%) had GBV-C/HGV and TTV coinfection. In the 45 hemodialyzed patients, HBsAg, HCV RNA, GBV-C/HGV RNA and TTV DNA were detected in one (2.2%), two (4.4%), seven (15.5%) and 26 (57.7%). One (2.2%) patient had HBV and TTV coinfection, two (4.4%) HCV and TTV coinfection whereas four (8.8%) were coinfected with GBV-C/HGV and TTV. No differences regarding age, gender, previous surgery and number of transfusions were found between infected and uninfected patients within and between both groups. In conclusion, the prevalence of the viruses studied in predialysis may influence their prevalence in dialysis units.     

Genetic heterogeneity and molecular epidemiology of GB virus C/hepatitis G virus in China

OBJECTIVE: The inter- and intrapatient genetic variation of GB virus C (GBV-C)/hepatitis G virus (HGV) was investigated to characterize the molecular epidemiologic profile of GBV-C/ HGV infection in China, an area endemic for viral hepatitis. The intrapatient variation of hepatitis C virus (HCV) from the same patients was compared to that of GBV-C/HGV. STUDY DESIGN/METHODS: GB virus C/HGV RNA was amplified by polymerase chain reaction in 88 patients with hepatitis C, hepatitis B or presumed non-A-E hepatitis from three cities in China. Five clones of the GBV-C/HGV NS3 region were sequenced from each GBV-C/HGV RNA-positive patient. The corresponding region of HCV was also sequenced from patients co-infected with HCV. Representative sequences of the GBV-C/HGV NS3 region from each patient and those of isolates from other continents were subjected to phylogenetic analyses. RESULTS: GB virus C/HGV was detected in 22 (25.25%) of 88 patients: 9 (21.4%) of 42 patients with presumed non-A-E hepatitis, 10 (27.7%) of 36 patients with hepatitis C, 3 (30.0%) in 10 patients with hepatitis B and C, and in none of 60 volunteer blood donors. The extent of nucleotide variation was less between Chinese isolates (2.4-17%; median, 10.4%) than between Chinese isolates and seven isolates from outside China (10.5-19.5%; median, 15.3%). Intrapatient sequence variation ranged from 0 to 1.75%, with a mean of 0.57 +/- 0.51%. Phylogenetic analysis grouped most Chinese isolates into four geographically specific clusters with a divergence of 10% to 16% from each other. The ratio of nonsynonymous to synonymous substitutions of GBV-C/HGV (Ka/Ks 0.019) was much lower than for HCV (0.071) in the same patients. CONCLUSION: Chinese isolates of GBV-C/HGV are genetically distinct. There are local strains as well as shared strains between different locales. The extent of amino acid sequence conservation suggests strong selection against nonsynonymous substitutions in the GBV-C/HGV genome.     

Clinical significance of TT virus infection in patients with chronic liver disease and volunteer blood donors in Egypt

Clinical significance of TT virus (TTV) infection was investigated in Egyptian patients with chronic liver disease and volunteer blood donors by a cross sectional analysis. TTV DNA in serum was assessed by a semi-nested polymerase chain reaction. The prevalence of TTV DNA did not differ among patients with chronic hepatitis B (11/24, 46%), chronic hepatitis C (22/72, 31%), or schistosomal liver disease (14/39, 36%). No difference in prevalence was found between blood donors (32/109, 29%) and each of the patient groups. Clinical background including mean age, sex distribution, history of blood transfusion, and mean level of alanine aminotransferase did not differ between TTV DNA-positive and -negative individuals in any of the study groups. Ultrasonographic evidence of liver cirrhosis was similar between TTV-positive and -negative patients in each of the chronic liver disease groups. TTV infection was not associated with hepatitis B or C virus infection in blood donors. The only significant difference observed was the lower concentration of serum HCV RNA in TTV DNA positive compared with negative patients with chronic hepatitis C (3.0 +/- 1.4 vs. 4.0 +/- 0.9 log copies/ml, P <. 001). In conclusion, TTV infection was not associated with either past history of blood exposure or infection with bloodborne hepatitis viruses in Egypt. No clinical significance of TTV was found in the present study. However, a reciprocal interaction was suggested between TTV and HCV replication.     

Influence of hepatitis G virus infection on liver disease

The influence of hepatitis G virus (HGV) infection on disease activity in hepatitis C related and unrelated liver disease was investigated in 254 individuals using an EIA polymerase chain reaction assay for HGV. One hundred patients had chronic hepatitis C, 26 primary biliary cirrhosis, and 30 alcoholic liver cirrhosis. In addition, 51 hepatitis B surface antigen (HBsAg)-positive and 47 anti-hepatitis C virus (HCV)-positive blood donors were screened. Hepatitis G virus was detected in 18% of patients with chronic hepatitis C, 13% of patients with alcoholic liver cirrhosis, 11 % of patients with primary biliary cirrhosis, 10% of anti-HCV-positive blood donors, and 2% of HBsAg-positive blood donors. Virus load and alanine aminotransferase (ALT) levels did not differ significantly in patients with HCV alone versus patients coinfected with HCV and HGV. However, mild liver fibrosis correlated with HGV coinfection. Hepatitis G virus did not influence ALT levels or liver damage in liver disease unrelated to viral infection.     

Profiles of GBV-C/hepatitis G virus markers in patients coinfected with hepatitis C virus.

GBV-C/Hepatitis G virus (GBV-C/HGV) is a newly discovered viral agent, found widely among healthy blood donors and among individuals at risk of parenterally transmitted infections. GBV-C/HGV is found frequently in coinfection with HCV. A population of 109 HCV positive patients was examined for the presence of GBV-C/HGV RNA and antibodies to E2. Of the 109 patients, 23 (21%) had serum GBV-C/HGV RNA in serum, 39 (36%) had only antibodies to E2 and 8 (7%) were positive for both markers, with an overall prevalence of 64%. Different serologic and virological patterns were observed in GBV-C/HGV exposed patients according to their infection status. Active infection was characterized by positive RT/PCR signal with primers for both the 5'UTR and NS5 genomic regions, viremia levels above 10(4) copies/mL by real time quantitative RT/PCR and absence of detectable anti-E2. In the transition phase between active infection and recovery, GBV-C/HGV RNA was only detectable by RT/PCR using primers from the 5' untranslated region and viremia levels were below 10(4) copies/ml by quantitative PCR, with or without simultaneous presence of anti-E2 antibodies. Resolved infection was characterized by absence of detectable viremia and, in most patients, by the presence of anti-E2.     

Seroepidemiology of TT virus, GBC-C/HGV, and hepatitis viruses B, C, and E among women in a rural area of Tanzania

The seroprevalence and determinants of hepatitis B, C, and E virus infection, and of GBV-C/hepatitis G virus and TT virus infection were investigated among women from a rural area of northeastern Tanzania. High seroprevalence rates were found for TTV (74%), HBV (74%), and GBV-C/HGV (35%), whereas 7% of the women had evidence of HCV and HEV infection. The majority of TTV DNA sequences in the study population belonged to the genotypes 1 or 2. One sequence seems to represent a new subtype of genotype 4. The GBV-C/HGV sequences either belonged to the genomic Group 1b or to the recently described Group 4. In multivariate analysis, the detection of TTV DNA was associated significantly with a larger number of children in the household and with older age. A history of injections of contraceptive hormones was an independent risk factor for HCV infection. The findings on TTV are consistent with fecal-oral transmission, and recurrent infections may occur in adults.     

Frequencies of GB virus C/hepatitis G virus genomes and of specific antibodies in German risk and non-risk populations

The prevalence of the new flavivirus GB virus C/hepatitis virus G (GBV-C/HGV) in different German populations was investigated by detection of viral genomes and anti-E2 antibodies. While blood donors had an overall prevalence of 10.4% there were increased rates for hemophiliacs (54.7%), hemodialysis patients (30.2%), male homosexuals (30.2%) and intravenous drug users (74.4%). Most GBV-C/HGV positive samples were either viral genome positive or antibody positive, exclusively. Samples with the rare constellation “positive for both GBV-C/HGV genome and specific antibody” originated in almost all cases from patients who were additionally infected with HIV or HCV. Probable transmission of GBV-C/HGV by PCR-positive blood transfusions was observed in 5 of 6 cases approximately six months after transfusion. J. Med. Virol. 53:218–224, 1997. © 1997 Wiley-Liss, Inc.     

Interspousal transmission of GB virus-C/hepatitis G virus: A comparison with hepatitis C virus

Although infection with GB virus-C/hepatitis G virus (GBV-C/HGV) by blood transfusion is well documented, little is known about the other routes of transmission. The prevalence of GBV-C/HGV infection in spouses of index patients and the related risk factors were studied. Hepatitis C virus (HCV) and GBV-C/HGV infections were studied in spouses of 100 patients with hepatitis C, of whom 12 were found to be also positive for GBV-C/HGV RNA. For couples both with GBV-C/HGV viremia, nucleotide sequences of the divergent envelope region were analyzed by phylogenetic tree constructions. For HCV infection, anti-HCV was found in 14 (14%) of the 100 spouses. Five spouses (42%) of the 12 patients with dual infection of GBV-C/HGV and HCV had evidence of GBV-C/HGV infection, three had viral RNA, and two had antibodies to a recombinant HGV envelope protein E2. Nucleotide sequence comparison and phylogenetic tree analysis of the genome in the GBV-C/HGV infected couple revealed the isolates to be closely related. These results suggest that spouses of patients with GBV-C/HGV infection are at a higher risk of acquiring GBV-C/HGV as compared with HCV, and they should be educated to avoid GBV-C/HGV infection from their spouses, in case GBV-C/HGV is shown to be pathogenic. J. Med. Virol. 53:348–353, 1997. © 1997 Wiley-Liss, Inc.