Seroprevalence of GB virus C/hepatitis G virus-RNA and anti-envelope antibody in high-risk populations in Taiwan

BACKGROUND: GB Virus C (GBV-C)/hepatitis G virus (HGV) was identified in 1995-1996 as a transfusion-transmissible virus. The diagnosis of GBV-C/HGV infection is based on the detection of GBV-C/HGV-RNA by using polymerase chain reaction. Recently, an enzyme immunoassay detecting the antibodies to the viral protein, E2 envelope protein (anti-envelope) of GBV-C/HGV, has been developed. METHODS: Serum GBV-C/HGV-RNA and anti-envelope antibody were determined in 76 cases of intravenous drug users (IVDU), 76 patients with regular hemodialysis and in 80 prostitutes to evaluate the GBV-C/HGV infection rate among high-risk populations in Taiwan. Seventy-six healthy blood donors were randomly selected and were used as a control group. RESULTS: The prevalence of GBV-C/HGV-RNA in high-risk populations was 33% for IVDU, 16% for patients with hemodialysis and 13% for prostitutes, which was significantly higher than the 3% obtained in the control group (P < 0.05 for all groups). The prevalence of anti-envelope antibody was 13% for IVDU, 21% for patients with hemodialysis and 23% for prostitutes, which was not significantly different from the control group (11%). Among the 99 subjects who had positive GBV-C/HGV markers, 97 were tested for exclusive positivity for either GBV-C/HGV-RNA or anti-envelope antibody. CONCLUSIONS: The presence of serum anti-envelope antibody usually indicates the clearance of serum GBV-C/HGV-RNA in patients infected with GBV-C/HGV. GBVirus-C/HGV infection in high-risk populations, determined by the presence of serum GBV-C/HGV-RNA, may underestimate the true level of past and present infection.     

Minimal role of GB virus-C/hepatitis G virus in fulminant and subfulminant hepatitis in Taiwan

BACKGROUND: The role of GB virus-C/hepatitis G virus (GBV-C/HGV) in fulminant hepatitis (FH) and subfulminant hepatitis (SFH) remains unclear. METHODS: Thirty-two FH or SFH patients, with adequate clinical information and serum specimens, were studied. Serum samples were tested for hepatitis markers and genomes of hepatitis A-E viruses, as well as GBV-C/HGV. RESULTS: Of the cases of FH/SFH studied, one (3%) was caused by anti-tuberculosis agents, 26 (81%) had hepatotropic virus infection, and five (16%) had no identifiable cause. Of the 26 patients with hepatotropic virus infection, five had acute hepatitis B infection (one with acute hepatitis D virus (HDV) co-infection), one had acute hepatitis C infection, 16 were hepatitis B surface antigen carriers with reactivation or superimposed by unidentified agent(s) (two had triple virus infections), three were hepatitis B carriers with HDV superinfection, and one had GBV-C/HGV infection in addition to exposure to halothane. GBV-C/HGV-RNA was detected in only three of 32 patients (9%) and all had a history of blood transfusion or co-existing causative factors. Of the 26 patients with hepatotropic virus infection, 18 were tested for antibodies against GBV-C/HGV envelope protein and seven were reactive, suggesting past infection. CONCLUSIONS: The role of GBV-C/HGV in causing FH and SFH is minimal in Taiwan and HBV infection remains the major aetiology. These findings also suggest the existence of as yet unrecognized agents, responsible for such catastrophic illnesses.     

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.     

Influence of RNA titre and amino acid changes in the NS5A region of GB virus c/hepatitis G virus on the effectiveness of interferon therapy

BACKGROUND: A relationship between the pretreatment RNA titre of GB virus C/hepatitis G virus (GBV-C/HGV) and the effectiveness of interferon (IFN) therapy has been reported previously. However, the influence of changes in the amino acid sequence of the NS5A region of GBV-C/HGV on the effectiveness of IFN therapy has not been examined, although this influence has been explored in patients with chronic hepatitis caused by hepatitis C virus. We examined the relationship between changes in the amino-acid sequence of the NS5A region and the effectiveness of IFN therapy. METHODS: The subjects were 10 patients with chronic hepatitis C coinfected with GBV-C/HGV and treated with IFN. The pretreatment level of GBV-C/HGV-RNA (copies/mL) in their sera was measured by real-time detection polymerase chain reaction (PCR) assay. At 6 months after cessation of therapy, four of 10 patients had become negative for GBV-C/HGV-RNA (CR, complete response) and six patients were still positive for GBV-C/HGV-RNA (NR, non-response). We determined the nucleotide sequence of the NS5A region (amino acid residues 1865-2279; NS5A1865-2279) of pretreatment GBVC/HGV-RNA by direct sequencing. RESULTS: The pretreatment GBV-C/HGV-RNA level of CR patients (7.8 x 10(4) - 6.2 x 10(5), mean 3.30 x 10(5)) was significantly lower than that of NR patients (6.3 x 10(7) - 7.2 x 10(8), mean 3.55 x 10(8); P< 0.01). The number of amino acid substitutions in NS5A1865-2279 was five to seven (mean 5.8 +/- 1.0) in CR patients, and four to eight (mean 6.8 +/- 1.6) in NR patients, a difference that is not significant. Moreover, there were no amino acid substitutions or sites of substitution in NS5A1865-2279 that were specific to either group. CONCLUSIONS: The effectiveness of IFN therapy for GBV-C/HGV is strongly related to the pretreatment GBV-C/HGV-RNA level, but is not related to changes in NS5A1865-2279.     

Influence of GB virus-C/hepatitis G virus infection on the long-term course of chronic hepatitis B

Abstract: Aims/Background: The clinical significance of GB virus-C/hepatitis G virus (GBV-C/HGV) infection in chronic hepatitis B is not well known and its role in the outcome of liver disease was investigated. Methods: HGV-RNA and antibody to HGV (anti-E2) were studied in 125 patients with chronic hepatitis B (41 with multiple hepatitis virus exposure), 82 asymptomatic HBsAg carriers and 103 healthy adults. Results: In chronic hepatitis B, HGV-RNA was more frequent in patients with HDV infection and/or anti-HCV positivity than in those without (29% vs 6%, p<0.0001), mainly in drug addicts (38%). At diagnosis the overall prevalence of any marker (HGV-RNA plus anti-E2) was similar in chronic hepatitis due to HBV alone (17%), in HBsAg carriers (16%) and in healthy adults (17%) and increased to 58% in those exposed to HDV and/or HCV. During 1–11 years of follow-up, HGV infection persisted in 70% of patients with chronic hepatitis B. About 40% of HGV persistently coinfected patients underwent sustained biochemical remission, whereas continuing disease activity was observed in 80% of patients who cleared HGV-RNA. Conclusions: In chronic HBV infection the rate of exposure to HGV is similar to that in healthy adults, except for high risk patients. Long lasting HGV coinfection or anti-E2 seroconversion did not modify the course of chronic hepatitis B.     

BRIEF COMMUNICATION: Efficacy of ribavirin plus interferon α on viraemia of GB virus-C/hepatitis G virus: Comparison with interferon α alone

We investigated the efficacy of ribavirin plus interferon (IFN) α on GB virus-C (GBV-C)/hepatitis G virus (HGV) viraemia and compared it with that of interferon α alone in patients coinfected with hepatitis C virus (HCV) and GBV-C/HGV. Serum HCV and GBV-C/HGV-RNA were studied in eight patients with HCV and GBV-C/HGV coinfection, five received IFNα and three received oral ribavirin plus IFNα. Mean serum GBV-C/HGV titre at the end of therapy was significantly lower than the titre just before therapy and patients with lower pretreatment titre had a better sustained response rate. Sustained virological response of GBV-C/HGV to IFNα alone and ribavirin plus IFNα at the end of follow up was observed in one each, respectively. Thus, GBV-C/HGV in patients with HCV and GBV-C/HGV coinfection does respond to IFNα and ribavirin plus IFNα may not induce a higher sustained response.     

GBV-C/HGV在血清学非甲～戊型急性肝炎发生中的作用

探讨GBV-C/HGV在血清学非甲～戊型急性肝炎发生中的作用及临床意义.采用免疫组化方法对56例血清学非甲～戊型急性肝炎患者肝组织标本进行GBV-C/HGV NS5抗原的检测,结合临床资料进行分析.血清学非甲～戊型急性肝炎肝组织中GBV-C/HGV NS5抗原检出率为53.6%,主要是以和HBV/HCV重叠感染的形式存在,重叠感染组的ALT升高和HBV/HCV感染组差异无显著意义.单纯GBV-C/HGV感染占16.1%,所引起的血清ALT升高明显低于HBV/HCV感染,而与病原不明病例差异无显著意义.GBV-C/HGV可能没有致病性或者有弱致病性,不是血清学非甲～戊型急性肝炎的主要致病因子.     

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.     

Clinical significance of hepatitis G virus infection in patients on long-term haemodialysis

Infection with the newly discovered hepatitis G virus (HGV) was analysed in 163 patients on long-term haemodialysis to clarify its prevalence and clinical significance. Hepatitis G virus RNA in serum was measured by polymerase chain reaction with primers corresponding to the putative non-structural 5’ region. Of the 163 patients, three (1.8%) were positive for hepatitis B surface antigen, 40 (24.5%) were positive for hepatitis C virus (HCV)-RNA and 16 (9.8%) were positive for HGV-RNA. Five of the 16 patients with HGV-RNA were also positive for HCV-RNA. Patients with HCV and HGV coinfection had undergone a longer duration of haemodialysis (P=0.001) and had higher units of transfusion (P=0.031) compared with those without hepatitis virus infection. Transfusion history was significantly higher (P=0.039) in patients with only HGV infection than in those without hepatitis virus infection. Hepatitis C virus RNA concentration was higher (P=0.032) in patients with HCV and HGV coinfection than in those with HCV infection only, but alanine aminotransferase (ALT) levels were similar between these two groups. In conclusion, about 10% of patients on haemodialysis were infected with HGV and the infection was closely associated with transfusion history.     

GB Virus C/Hepatitis G Virus Infections in Traumatologic Outpatients, Chronic Non-A-E Hepatitis and Extrahepatic Malignancies

Summary GB virus C/hepatitis G virus (GBV-C/HGV) is a recently discovered flavivirus of still unknown pathogenic relevance. We examined traumatologic outpatients to determine GBV-C/HGV viremia for further epidemiological studies, as blood donors hitherto used as controls represent healthy individuals without risk factors. Anti-GBV-C/HGV antibodies were detectable in 13.2% (95% confidence interval [CI] 9.3–18.2) and GBV-C/HGV RNA was detectable in 4.5% (95% CI 2.4–8.2) of the outpatients. In chronic non-A-E hepatitis patients GBV-C/HGV viremia was detectable at a significantly higher level of 16.1% (95% CI 6.1–:34.5), while the prevalence of anti-GBV-C/HGV antibodies was 12.9% (95% CI 4.2–30.8). The rate of GBV-C/HGV viremia in patients with malignant diseases (different types of tumors, blood recipients were excluded) was 12.5% (95% CI 8.4– 18.1), a significant elevation compared to traumatologic outpatients. The seroprevalence in the tumor group was 22.1% (95% CI 16.7–28.6), also significantly elevated. Thus, there are two messages. Firstly, testing for GBV-C/HGV may be a useful extension of the diagnostic procedure of viral hepatitis. Secondly, common risk factors or etiologic relations of GBV-C/HGV and extrahepatic malignancies should be discussed. Received: March 29, 1999 · Revision accepted: November 22, 1999     

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.     

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.     

Hepatitis G virus in multitransfused thalassaemics from India

Hepatitis G virus (HGV)/GB virus-C (GBV-C) has been identified as a blood-borne agent with disputed pathogenicity. This virus belongs to the flaviviridae with a distant relationship to hepatitis C virus (HCV). Genetically divergent HGV isolates have been reported from different parts of the world. This study describes the prevalence of HGV in multitransfused thalassaemic children in India and genomic sequence variations in 11 HGV isolates from the same geographical location. Hepatitis G virus RNA was detected in 39.7% multitransfused thalassaemic children. The seroprevalence of hepatitis B virus (HBV) and HCV was 23.8% and 17.1%, respectively, and 11.4% had dual infection. The nucleotide sequence of a 166 bp HGV genomic segment from the putative capsid-envelope region (nucleotide; nt 578–743) from 11 Indian isolates was compared to the sequences available in the nucleotide databases. The isolates from India were 81.3–94.5% homologous to the isolates from other parts of the world. On phylogenetic analysis, it was observed that HGV isolates from India may belong to two genetically divergent types.     

Comparative study of 5‘ UTR and NS3R primers for the detection of GB virus C/ hepatitis G virus RNA in Japanese

Abstract: Aims/Background: Many epidemiological studies of new hepatitis viruses, including GB virus C (GBV-C) and hepatitis G virus (HGV), have used polymerase chain reaction (PCR) primers designed for the third nonstructural region (NS3R). However, a homology study of GBV-C and HGV genomes revealed that the 5′ untranslated region (5'UTR) was more conserved than NS3R. Methods: We attempted to detect GBV-C/HGV using PCR primers corresponding to the 5′ UTR, and compared its incidence to that derived from NS3R primers. Furthermore, PCR products amplified using the 5′ UTR primers were sequenced and subjected to phylogenetic analysis. Results: In patients with chronic hepatitis C, the prevalence of GBV-C/HGV by PCR with the NS3R and 5′ UTR primers was 5.1% (4/78) and 17.9% (14/78), respectively, and in patients on hemodialysis, it was 0% (0/81) and 5.9% (5/85), respectively. We could not detect GBV-C/HGV in patients with non-A-C liver disease. The incidence of GBV-C/HGV by 5′ UTR primers was higher than by NS3R primers. After DNA sequencing at 5′ UTR, phylogenetic analysis showed two types of GBV-C/HGV, Jap and HGV types. Conclusion: 5′ UTR primers proved highly sensitive for detection of GBV-C/HGV and were superior to the NS3R primers.     

A study on pathogenicity of hepatitis G virus

AIM: To study the pathogenicity of hepatitis G virus (HGV) and observe the genesis and pathological process of hepatitis G. METHODS: HGV-RNA in serum was detected by RT-PCR assay. The immunohistochemical assays of liver tissue were performed with HGV monocoloned antibody (McAb) expressed from the region of HGV NS5 nucleic acid sequence. The clinical and pathological data of 52 patients with hepatitis G were discussed. In animal experiment, the Chinese Rhesus monkeys were infected with the serum of a patient with HGV infection. And the dynamic changes in serology and liver histology of animals were observed. RESULTS: One hundred and fifty-four patients with HGV-RNA positive were selected from 1552 patients with various kinds of hepatitis. Of 154 patients with HGV infection, 52 were infected with HGV only, which accounted for 33.8 (52/154) and 102 with positive HGV-RNA were super-infected with other hepatitis viruses, which accounted for 66.2 (102/154). The clinical and pathological observation showed that the acute and chronic hepatitis could be induced by HGV. The slight abnormality of transaminases ALT and AST in serum of monkeys lasted nearly 12 months and histological results showed a series of pathological changes. CONCLUSION: HGV is a hepatotropic virus and has pathogenicty.