Analysis of hepatitis G virus (HGV) RNA, antibody to HGV envelope protein, and risk factors for blood donors coinfected with HGV and hepatitis C virus

Serologic, biochemical, and molecular analyses were used to study hepatitis G virus (HGV), antibody to the HGV envelope protein (anti-E2), risk factors, clinical significance, and the impact of HGV on coexistent hepatitis C virus (HCV). Among 329 donors with confirmed HCV infection, 12% were HGV RNA-positive and 44% were anti-E2-positive (total exposure, 56%). HGV RNA and anti-E2 were mutually exclusive except in 9 donors (1.5%); 8 of 9 subsequently lost HGV RNA but anti-E2 persisted. HGV had little impact on alanine aminotransferase, aspartate aminotransferase, or gamma-glutamyl transpeptidase in donors with HGV infection alone or those coinfected with HCV. A multivariate analysis showed that intravenous drug abuse was the leading risk factor for HGV transmission, followed by blood transfusion, snorting cocaine, imprisonment, and a history of sexually transmitted diseases. In summary, HGV and HCV infections were frequently associated and shared common parenteral risk factors; HGV did not appear to cause hepatitis or to worsen the course of coexistent hepatitis C.     

Analysis of hepatitis G virus infection markers in blood donors and patients with hepatitis

The incidence and clinical significance of hepatitis G virus (HGV) is still not fully known. The aim of our study was to assess the frequency of HGV RNA and antibody to HGV E2 protein (anti-E2) in Polish blood donors and patients with hepatitis, and to compare the sequence of HGV clones with those reported by others. Two-hundred and nineteen blood donors and 83 patients with hepatitis were studied. HGV was detected in 3.2% and anti-E2 in 24.2% of blood donors and in 26.5% and 8.4% of patients with hepatitis, respectively. HGV was detected as a co-infection with HCV in four of 18 patients with chronic hepatitis, in four of 16 patients with acute hepatitis and in one of six patients with fulminant liver failure (FLF), and as a co-infection with HBV in one of six patients with FLF and in three of 10 patients with chronic hepatitis. In non-A–C hepatitis, eight of 23 patients with acute hepatitis and one of four patients with FLF were positive for HGV but all 10 patients with chronic cryptogenic hepatitis were negative. In the follow-up studies of patients with HGV alone, a correlation with viraemia and clinical symptoms was observed in two patients, but in three others HGV RNA was detected in spite of clinical resolution. Two HGV clones were sequenced, and the sequence of the HGV helicase region of the HGV isolates from donor and patient were homologous to those described by others. Hence, the frequency of HGV RNA in blood donors is similar to that obtained in other countries but the anti-E2 (marker of a past infection) frequency is higher. The incidence of HGV RNA and anti-E2 in hepatitis patients suggests that HGV plays a role in liver pathology, but careful analysis of individual cases does not confirm this.     

Liver histology in co-infection of hepatitis C virus (HCV) and hepatitis G virus (HGV)

As little is known about liver histology in the co-infection of hepatitis C virus (HCV) and hepatitis G virus (HGV), HGV RNA was investigated in 46 blood donors with hepatitis C, 22 of them with liver biopsy: co-infection HCV / HGV (n = 6) and HCV isolated infection (n = 16). Besides staging and grading of inflammation at portal, peri-portal and lobular areas (Brazilian Consensus), the fibrosis progression index was also calculated. All patients had no symptoms or signs of liver disease and prevalence of HGV / HCV co-infection was 15.2%. Most patients had mild liver disease and fibrosis progression index, calculated only in patients with known duration of infection, was 0.110 for co-infection and 0.130 for isolated HCV infection, characterizing these patients as "slow fibrosers". No statistical differences could be found between the groups, although a lesser degree of inflammation was always present in co-infection. In conclusion co-infection HCV / HGV does not induce a more aggressive liver disease, supporting the hypothesis that HGV is not pathogenic.     

Epidemiological and Clinical Aspects of Hepatitis G Virus Infection in Blood Donors and Immunocompromised Recipients of HGV-Contaminated Blood

Background and objectives: The infectiousness and clinical relevance of the newly discovered blood-borne Flaviviridae-like agent, termed hepatitis G virus (HGV), are not well understood. Materials and methods: Twenty-three transfusion recipients of two HGV-affected long-term blood donors were studied for HGV genome and antibodies to the putative envelope 2 glycoprotein (anti-E2) of HGV. Nine recipients had nonhematological disorders and 14 suffered from severe hematological diseases and 7 of them received allogeneic bone marrow or blood stem cell transplantation. The molecular epidemiology of the observed HGV infection was studied by direct sequencing of parts of the 5′-noncoding region, NS3, and NS5 region of HGV in the 2 long-term donors and in their 6 recipients who became HGV RNA positive. Additionally, 549 individuals – homologous (n = 254) and autologous blood donors (n = 202), and medical staff (n = 89) – were investigated for the presence of HGV RNA. Results: HGV RNA in serum was found in 15 of the 23 (65%) transfusion reciients with known exposure of HGV-contaminated blood. Seven of the remaining 8 recipients showed only an anti-E2 response, indicating previous HGV infection with spontaneous clearance of the virus. In one recipient neither HGV RNA nor anti-E2 could be detected. Molecular evidence for HGV transmission by the 2 donors was found in 3 of the 6 recipients studied. The alanine aminotransferase levels were not significantly different in the HGV RNA positive and negative recipients, and none of the 23 recipients developed posttransfusion hepatitis. Persistent HGV infection was observed especially in recipients with severe hematological disorders or in those in whome intensive immunosuppressive treatment was necessary. Of the 549 individuals studied, 10 (1.8%) were healthy carriers of HGV RNA. Conclusion: The persistence of transfusion-acquired HGV infection is not associated with acute or chronic hepatitis, but may be influenced by the recipient's underlying disease.     

GB virus-C/hepatitis G virus infection in a hepatitis C virus endemic village: prevalence in residents with low educational attainment and frequent recovery in females

AIMS/BACKGROUND: GB virus-C/hepatitis G virus (HGV) is a newly identified flavivirus, which may share the same mode of transmission as hepatitis C virus (HCV). The aim of this study was to investigate associated factors of HGV infection and clearance in a HCV endemic village in southern Taiwan. METHODS: Five hundred and ninety-four residents of a village in southern Taiwan were enrolled for hepatitis virus screening. Clinical features were recorded and a questionnaire addressing the possible routes of transmission was filled in by the participating residents. RESULTS: The prevalence of antibody to hepatitis C virus and hepatitis B surface antigen in the 594 residents was 70.7% and 19.5% respectively. Of the 399 residents tested for HGV RNA, GB virus-C/Hepatitis G virus envelop 2 protein (HGV-E2) antibody, and HCV RNA, the prevalence was 13.5%, 25.3%, 53.1% respectively. Multivariate logistic regression analysis showed that low educational attainment was associated with HGV infection, old age and low educational attainment were associated with HCV infection, and female gender was associated with HGV clearance. Alanine aminotransferase (ALT) values were significantly higher for residents with HCV infection alone, HBV infection alone, and co-infection of HCV and HBV than for those without HBV, HCV, and HGV infection. There were no differences in ALT values between subjects with HGV infection alone and those without HBV, HCV, and HGV infections. Residents with co-infection of HGV and HBV, or HGV and HCV had ALT values similar to those with HBV or HCV infection alone. CONCLUSION: HGV infection is common in the HCV endemic village. The transmission of HGV is closely related to low educational attainment. HGV clearance is frequently encountered in females. Co-infection of HGV does not compound hepatocellular inflammation.     

The epidemiology of TT virus (TTV) infection in a hepatitis C and B virus hyperendemic area of southern Taiwan

TT virus (TTV) is a newly isolated DNA virus from the serum of a patient with posttransfusion hepatitis of unknown etiology in 1997. To evaluate the clinical and molecular characteristics of TT virus (TTV) in a hepatitis C virus (HCV) and B (HBV) hyperendemic area (Masago), 200 residents were enrolled in the study. The sera were tested for alanine aminotransferase (ALT), HCV RNA and GB virus C/Hepatitis G virus (HGV) RNA, TTV DNA, HBsAg, anti-HCV and antibodies to HGV E2-protein (anti-E2). TTV DNA was positive in 99 of the 200 sera with a prevalence rate of 49.5%. The prevalence of HBsAg, anti-HCV, HCV RNA, HGV RNA, anti-E2 and HGV exposure (defined as positive for serum HGV RNA and/or anti-E2) was 38.9%, 69.5%, 64.5%, 17.0%, 25.5% and 39.5%, respectively. Neither clinical nor virological factors were associated with TTV viremia. The rate of ALT abnormality was significantly elevated in HCV RNA-positive (34.9%) than -negative (7.0%) residents (p < 0.001). HCV viremia was the only factor significantly associated with ALT elevation by multiple logistic regression (odds ratio: 6.96; 95% C.I.: 2.60-18.7). We concluded that in this HCV/HBV hyperendemic area, the prevalence of TTV DNA was high. No significant clinical factor was observed to be associated with TTV infection. TTV infection is not related to abnormal ALT levels and ALT abnormality was mainly attributable to HCV but not TTV, HBV or HGV infection.     

A case-control study of transmission routes for GB virus C/hepatitis G virus in Swedish blood donors lacking markers for hepatitis C virus infection.

BACKGROUND AND OBJECTIVES: The transmission routes for GB virus-C (GBV-C)/hepatitis G virus (HGV) in blood donors unexposed to hepatitis C virus (HCV) are unknown. We performed a case-control study of risk factors for GBV-C/HGV exposure in blood donors. MATERIALS AND METHODS: After testing stored sera from 458 HCV-negative blood donors for GBV-C/HGV RNA and GBV-C/HGV E2 antibodies, 66 donors with GBV-C/HGV markers and 125 age- and gender-matched controls were interviewed regarding risk factors for viral transmission. RESULTS: Exposure to GBV-C/HGV was strongly associated with previous treatment for a sexually transmitted disease (odds ratio [OR] 4.6; 95% confidence interval [CI] 2.2-9.8), with multiple sexual partners (OR 2.9; 95% CI 1.4-5.7) and with a past history of endoscopy (OR 7.0; 95% CI 3.0-16.4). CONCLUSIONS: In blood donors with GBV-C/HGV markers, sexual contacts and medical procedures appear to be the main transmission routes.     

Prevalence of GBV-C/hepatitis G virus viremia and anti-E2 in Canadian blood donors

BACKGROUND AND OBJECTIVES: GB virus C (GBV-C)/hepatitis G virus (HGV) is a recently recognized parenterally and sexually transmitted agent. The prevalence of GBV-C/HGV markers in Canadian blood donors has not been previously studied and was therefore determined. MATERIALS AND METHODS: Blood donors [identity unlinked (IU), short-term temporarily deferred (STTD) and autologous groups] and donor samples with antibodies to hepatitis C (anti-HCV) or hepatitis B core were tested for GBV-C/HGV RNA and for antibodies to E2 antigen (anti-E2). RESULTS: GBV-C/HGV RNA was found in 1.1% and anti-E2 in 7.3% of the combined IU/STTD donor group. Viremia was much more common in anti-HCV-positive samples (12.5%); anti-E2 was present in >50% of this group. In the STTD group, female gender was significantly associated with viremia. CONCLUSION: GBV-C/HGV infection is relatively common in Canadian donors, and a small proportion are viremic. The association of female gender and viremia was unexpected. Further study is needed to clarify the epidemiology and natural history of GBV-C/HGV infection.     

Hepatitis G virus RNA and its relation to hepatitis C infection in adult haemophilic patients

The prevalence of hepatitis C virus (HCV) infection and hepatitis G virus (HGV) RNA were studied in 50 adult haemophilic patients who had received commercial clotting factors prior to 1980. HGV RNA was detectable in 6/50 patients (12%); 49/50 (98%) had antibody to HCV and 40/49 (82%) of these were viraemic with detectable HCV RNA; 5/6 patients with detectable HGV RNA had co-existing HCV infection and viraemia. The HGV PCR products from all six patients were directly sequenced and all were shown to be similar to that of HGV but more diverse from that of GB virus C. One patient who had persistent abnormal liver function tests had detectable HGV RNA but no evidence of hepatitis B or C. The presence of HGV RNA in the absence of hepatitis B and C infection indicates that this virus is capable of independent transmission. Independent response to interferon was demonstrated in one patient with co-infection who lost HGV but not HCV after interferon therapy.     

Prevalence and Clinical Significance of SEN Virus Infection Among Volunteer Blood Donors in Southern Taiwan

Of the eight different isolates of SEN virus (SENV), SENV-D and SENV-H have been suggested associated with transfusion-associated hepatitis. The prevalence and clinical significance of these two SENV strains among blood donors in southern Taiwan were investigated in this study. Sera of 223 blood donors who were negative for serum hepatitis B surface antigen (HBsAg) and third-generation HCV antibody (anti-HCV) from a blood center of southern Taiwan were tested for alanine aminotransferase (ALT), GB virus C/hepatitis G virus (GBV-C/HGV) anti-envelope protein 2 (anti-E2) antibody and RNA, and SENV-D and -H DNA. Of the 223 donors, the prevalence of SENV-D and/or -H (SENV-D/H), SENV-D, SENV-H DNA, GBV-C/HGV RNA, and anti-E2 were 24.2, 19.7, 5.8, 2.2, and 8.5%. The donors with SENV-D DNA had a significantly higher mean age than those without (31.2 +/- 10.9 vs. 27.5 +/- 8.3 years; P = 0.014). No association between positive SENV DNA and gender, GBV-C/HGV exposure, mean ALT level, or abnormal ALT was found. Based on multiple logistic regression analysis, the increased age was the only independent factor associated with positive SENV-D DNA (odds ratio, 1.042; 95% confidence interval, 1.01-1.08). Nearly a fourth of blood donors in southern Taiwan were infected by SENV-D/H, with SENV-D more prevalent than SENV-H. Patients with higher ages have a higher prevalence of SENV-D. SENV-D or SENV-H infection was not associated with ALT levels.     

Prevalence of hepatitis G virus RNA in a monocentric population of French haemophiliacs

Hepatitis G virus (HGV) and hepatitis GB virus (GBV-C) have been reported as possible causes of non-A–E transfusional hepatitis. To assess the prevalence of hepatitis G virus infection in haemophiliacs we retrospectively investigated the presence of viral RNA in 92 patients with and without HCV infection. HGV/GBV-C RNA was reverse transcribed and amplified with primers from the 5' non-coding region of the genome. RNA was detected in 16/92 patients (17.4%). Restriction enzyme analysis revealed that the 16 patients belonged to the HGV-like genotype. Serology with E2-specific antibodies demonstrated that HGV viraemia underestimates previous infection by HGV. 33 patients were positive for HGV; all but two have cleared HGV RNA. 47/92 patients had a marker of prior infection by HGV.
No difference between HGV RNA positive and negative patients was observed concerning age, diagnosis, HIV and HCV status. Previous HBV infection correlated with the frequency of HGV infection. There was no difference in alanine aminotransferase levels between HGV positive and negative patients. All 18 patients exposed to only virally inactivated plasma-derived concentrates were negative for both HGV RNA and anti E2 antibodies.
Prior exposure to untreated concentrates correlated with HGV viraemia ( P =0.03), HGV seropositivity ( P =0.0002), and markers of HGV infection ( P <0.0001).
In haemophiliacs with a past exposure to non-inactivated concentrates, persistence of HCV RNA (53/74 patients) was more frequent than HGV RNA persistence (16/74 patients) although HGV viraemia is more frequent than HCV viraemia in blood donors. This may be related to a greater ability of individuals to clear HGV infection and suggests that hepatitis G virus infection in multi-transfused patients has a better outcome than infection with other blood-borne viruses.     

Status and natural course of GB virus C/hepatitis G virus infection among high-risk groups and volunteer blood donors in Taiwan

BACKGROUND: Hemophilia, thalassemia and uremia patients are at risk of parenterally transmitted infectious agents. The status and nature of the course of GB virus C/hepatitis G virus (GBV-C/HGV) infection among these groups and blood donors in Taiwan was investigated. METHODS: Serum GBV-C HGV-RNA and antibodies to GBV-C/HGV envelope-2-protein (anti-E2) were determined in 500 blood donors and in 44 hemophilia, 37 thalassemia and 85 uremia patients. Phylogenetic analysis was performed. RESULTS: The prevalence of GBV-C/HGV-RNA and anti-E2, respectively, was 38.6 and 27.3% in hemophilia patients, 27.0 and 27.3% in thalassemia patients, 14.1 and 10.6% in uremia patients and 3.4 and 7.2% in blood donors. The prevalence of GBV-C HGV exposure was 59.1 and 51.4% in hemophilia and thalassemia patients, respectively, which was significantly higher than that for uremia patients (22.4%; P < 0.01) and blood donors (10.2%; P < 0.001). The anti-E2 seroconversion rate was 66.7% in blood donors and 47.4, 36.8 and 34.6% in thalassemia, uremia (P < 0.05 compared with blood donors) and hemophilia (P < 0.01 compared with blood donors) patients, respectively. Discrepancies in the prevalence of GBV-C HGV and hepatitis C virus infection were found among the three risk groups. Phylogenetic analysis showed that 51 of 56 GBV-C HGV isolates clustered in group 3; the remaining five were of group 2a. Twelve of 39 viremic patients in the risk groups cleared the virus during the 4 year follow-up period; seven developed concomitant anti-E2 reactivity. CONCLUSIONS: GB virus C hepatitis G virus infection is epidemic among risk groups and GBV-C HGV group 3 is the major strain in Taiwan. In the risk groups, approximately 18% of infections resolve with concomitant anti-E2 seroconversion within 4 years.     

HGV: the identification,biology and prevalence of an orphan virus

ABSTRACT— Hepatitis G virus (HGV) and GB virus C (GBV-C) (both hereinafter referred to as HGV) were independently identified in patients with hepatitis of unknown aetiology. HGV is a positive-sense RNA virus of the family Flaviviridae. The virus can establish both acute and chronic infection and appears to be sensitive to interferon. Horizontal transmission is mainly parenteral, although other routes such as vertical have been well documented. High risk groups include intravenous drug users (IVDUs), the multiply transfused, haemodialysis patients and haemophiliacs. Up to 90% of IVDUs are positive for either HGV-RNA or antibodies to HGV envelope-2 protein (anti-E2). HGV is frequently detected in patients with HBV and HCV infection. Its link to hepatitis has now become less certain. Only around 3–6% of non-A–E hepatitis cases are HGV viraemic, clearly showing that HGV is not the major cause of idiopathic hepatitis as originally hoped. Around 1–5% of volunteer blood donors in developed countries are HGV viraemic, but the prevalence is 10–20% in the general population in some developing countries. At present, it is not known whether HGV is associated with other diseases in humans, is a passenger virus, or only becomes virulent under certain conditions.     

Two patients with acute hepatitis B with suspected sexual transmission of hepatitis G virus

Two patients with acute hepatitis B with suggested sexual transmission of hepatitis G virus (HGV) are reported. A total of 18 patients with community acquired acute hepatitis B were analyzed in this study. Two of the 18 patients (patients 1 and 2) were positive for serum HGV RNA at the initial consultation. Both patients had had sexual contact with prostitutes several weeks before the onset of acute hepatitis, and hepatitis B virus (HBV) was suggested to be infected through the sexual contacts. These patients showed no other history of exposure to possible transmission routes for blood-borne hepatitis viruses. Patient 1 was diagnosed as with acute HGV infection because the antibody to HGV envelope-2 protein seroconverted to positive during the course of acute hepatitis. HGV RNA was negative in a serum sample collected from patient 2 before the onset of acute hepatitis, also suggesting acute HGV infection. These results indicate that in patients 1 and 2 HGV was infected along with HBV through sexual contact. The clinical manifestations of acute hepatitis in the two patients with HGV co-infection did not differ from those in the 16 patients with HBV infection alone. (Received Aug. 6, 1997; accepted Oct. 30, 1997)     

Impact of hepatitis G virus co-infection on the course of hepatitis C virus infection before and after liver transplantation

Background/Aims: Hepatitis G virus (HGV), a new RNA virus that is parenterally transmitted, has frequently been found in patients with chronic hepatitis C (HCV) infection but its role in chronic liver disease is unknown. The purpose of this study was to determine the prevalence of HGV infection in transplantation patients infected with hepatitis C and to assess the impact of HGV co-infection on the course of HCV infection after liver transplantation.Methods: Eighty-nine liver transplantation recipients with persistent hepatitis C viremia detected by polymerase chain reaction (PCR) were evaluated. Serum samples were tested before and after liver transplantation for HGV RNA by two different PCR methods: LC^TM assay (Abbott Laboratories) and an RT-PCR procedure which we developed using the silica gel technique for extraction of the HGV RNA. E2 antibodies were detected before orthotopic liver transplantation by an EIA-test. HCV RNA was quantified by branched DNA assay, and HCV genotype was determined. A mean of nine liver biopsy specimens were examined for each patient and the severity of the lesions was compared in HCV-positive patients with or without HGV co-infection.Results: The concordance between the two HGV RNA detection methods was excellent and the reproducibility of our RT-PCR procedure was confirmed. The prevalence of pretransplantation and posttransplantation HGV infection was 11% and 19%, respectively. Pretransplantation HGV infection was positively correlated with posttransplantation HGV infection (p<0.001). Before transplantation the E2 antibodies seroprevalence was 34%. Seven patients became HGV RNA positive after transplantation, but all of them were negative for E2 antibodies. Among the patients who remained RNA negative after liver transplantation, 40% were positive for E2 antibodies (p = 0.04). Pretransplantation clinical features (except AST mean value) were not different in patients with HCV and HGV co-infection and those with HCV only. After a mean follow-up of 34 months (range: 6 to 70), (75%) patients developed histological features of recurrent hepatitis but the frequency of the occurrence of graft hepatitis was not different between HGV/HCV co-infected patients and those with HCV alone (p=0.89). The mean interval from orthotopic liver transplantation to recurrence was 12.2 months (range: 3–63), which was not different for HVG/HVC-co-infected patients and HCV-infected patients. The histological severity of posttransplantation liver disease, and the graft and patient survival were not different for patients with and without HGV co-infection.Conclusions: Our results suggest the general persistence of HGV infection after liver transplantation, but HGV co-infection did not appear to influence the posttransplantation course of HCV infection. Before transplantation the prevalence of E2 antibodies was 34%, and our data clearly indicate that E2 antibodies were protective against HGV infection.     

G Virus in the General Population and in Patients on Hemodialysis

To determine the routes of transmission ofhepatitis G virus (HGV) and the relationship between HGVand hepatitis C virus (HCV) infections, we tested forHGV RNA by polymerase chain reaction and antibody to HCV (anti-HCV) in 494 hemodialysis patients,638 inhabitants of two HCV endemic areas, and in 400blood donors in Japan. HGV RNA was detected in 6.9% ofhemodialysis patients, in 1.4% of inhabitants, and in 0.8% of donors, and anti-HCV wasdetected in 39.3%, 12.4%, and 1.8%, respectively. Of HGVRNA-positive hemodialysis patients, and HGV RNA-positiveinhabitants, 64.7% and 11.1%, respectively, had been given blood transfusions. Theprevalences of HGV RNA and anti-HCV significantlyincreased with the duration of hemodialysis. Of all HGVRNA positives, 74.4% were coinfected with HCV andsubjects with HGV RNA alone had normal liver function.In conclusion, HGV is transmitted by blood transfusionand within the hemodialysis unit itself. HGV does notseem to injure hepatocytes.