GB virus C/hepatitis G virus infection in patients investigated for chronic liver disease and in the general population in southern Sweden

Serum samples from patients referred for liver biopsy for investigation of suspected chronic liver disease (n = 286) and from healthy middle-aged volunteers (n = 445) were analyzed for markers of exposure to GB virus C/hepatitis G virus (GBV-C/HGV), hepatitis B virus and hepatitis C virus. GBV-C/HGV analyses included GBV-C/HGV PCR for detection of viremia and GBV-C/HGV enzyme-linked immunosorbent assay for anti-GBV-C/HGV E2 antibodies. Liver biopsies were re-evaluated by a hepatopathologist. GBV-C/HGV markers were detected in 97/286 (34%) patients (GBV-C/HGV RNA = 26; anti-GBV-C/HGV E2 antibodies = 74) compared to 86/445 (19%; p < 0.0001) controls (GBV-C/HGV RNA = 7, anti-GBB-C/HGV E2 antibodies = 79). A significantly higher proportion of GBV-C/HGV-exposed subjects in the patient group were viremic compared to controls (27% vs. 8.1%; p = 0.0015). GBV-C/HGV markers were more commonly found in patients with chronic hepatitis B and C. In patients with GBV-C/HGV viremia, a higher occurrence of bile duct degeneration was detected than in non-viremic patients. Markers of GBV-C/HGV infection were over-represented among patients investigated for chronic liver disease, and ongoing GBV-C/HGV viremia was more common in this group than in controls. Apart from a higher prevalence of bile duct degeneration in viremic patients, infection with GBV-C/HGV did not confer any specific histological characteristics.     

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.     

GB virus C/hepatitis G virus infection among patients with hepatocellular carcinoma in the inshore area of the Yangtze river, China

To investigate the association between GB virus C/hepatitis G virus (GBV-C/HGV) infection and the development of hepatocellular carcinoma (HCC) in H city, in the inshore area of the Yangtze River, where high prevalence of HCC has been reported, we determined hepatitis B virus (HBV) and hepatitis C virus (HCV) markers, GBV-C/HGV-RNA and GBV-C/HGV E₂ antibody (anti-HG E₂) among 114 HCC patients and the same number of age- and sex-matched controls. There were no significant differences in the clinical and demographic characteristics between them, except for serum alanine aminotransferase level and history of liver diseases. There was a significant difference of hepatitis B virus surface antigen (HBsAg) prevalence between the HCC patients (75.4%) and the controls (20.2%; P < 0.01). Hepatitis C virus antibody was detected in 4.4% of the HCC patients, compared with 1.7% of the controls. GB virus-C/HGV-RNA and anti-HG E₂ were detected in 14.9 and 1.7% of the HCC patients, respectively, compared with 7.0 and 1.7% of the controls, respectively. Nucleotide sequences and molecular evolutionary analysis showed the strains of GBV-C/HGV-RNA were classified into genotype 2 and 3 (HG and ASIA type). An effect analysis showed an odds ratio (OR) for developing HCC from GBV-C/HGV infection among HBsAg-positive subjects was 14.9, with a 95% CI of 4.9–45.4. HBsAg infection alone was 13.83 (95% CI 7.4–25.9) and GBV-C/HGV infection alone, 3.74 (95% CI 1.1–13.1), respectively. These data indicate that HBV infection is considered to be one of the major risk factors in patients with HCC and although GBV-C/HGV infection was observed in both the HCC and the control groups, it might not play an important role in the development of HCC in this area.     

临床肝病患者中庚型肝炎病毒(GBV-C/HGV)的感染

本文应用抗-HGV酶联免疫法(EIA)和逆转录套式聚合酶链反应法(RT-PCR)检测150份乙型、120份丙型、15份戊型和49份非甲-戊型肝炎患者血清。结果显示:乙肝、丙肝、戊肝和非甲-戊型肝炎患者中抗-HGV抗体的阳性率分别为22.0％(33/150)、25.0％(30/120)、33.3％(5/15)和40.1％(20/49)。其中乙型、丙型、戊型和非甲-戊型肝炎的抗-HGV抗体阳性者中,HGV RNA的阳性率分别为58.3％(7/12)、60.0％(6/10)、40.0％(2/5)和45.5％(9/12)。说明GBV-C/HGV可与HBV、HCV或HEV合并感染,该病毒可能引起临床型肝炎。     

Hepatitis G virus

A number of new hepatitis viruses （G, TT, SEN） were discovered late in the past century. We review the data available in the literature and our own findings suggesting that the new hepatitis G virus （HGV）, disclosed in the late 1990s, has been rather well studied. Analysis of many studies dealing with HGV mainly suggests the lymphotropicity of this virus. HGV or GBV-C has been ascertained to influence course and prognosis in the HIV-infected patient. Until now, the frequent presence of GBV-C in coinfections, hematological diseases, and biliary pathology gives no grounds to determine it as an ＂accidental tourist＂ that is of no significance. The similarity in properties of GBV-C and hepatitis C virus （HCV） offers the possibility of using HGV, and its induced experimental infection, as a model to study hepatitis C and to develop a hepatitis C vaccine.     

HGV/GBV-C感染在肝细胞损伤中的作用探讨

目的 研究单一HGV/GBV-C感染者肝组织中该病毒核酸定位及相关抗原表达,探讨HGV/GBV-C感染在肝细胞损伤中的作用。方法 12例单一HGV/GBV-C感染者经肝穿获取的肝组织常规病理诊断,采用地高辛标记探针原位杂交法检测病毒RNA,并用免疫组织化学法检测病毒相关抗原表达。结果 病理诊断急性肝炎8例,慢性肝炎4例。HGV/GBV-C NS5抗原检出阳性率为66.67％(8/12),阳性信号主要位于肝细胞胞浆中;HGV/GBV-C RNA检出阳性率为58.33％(7/12),阳性信号位于胞浆,分布无一定规律,阳性细胞与肝细胞变性、淤胆、炎性细胞浸润、细胞坏死程度等并无相关关系。单一HGV/GBV-C感染者临床表现轻,不易被发现。结论 HGV/GBV-C RNA并不直接损害肝细胞;肝细胞中存在HGV/GBV-C相关抗原表达,其编码产物可能作为一种靶抗原,诱发免疫病理反应。     

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.     

Detection of serologic responses to GB virus C/hepatitis G virus infection.

OBJECTIVES: To investigate the prevalence of GB virus C/hepatitis G virus (GBV-C/HGV) and compare the serologic responses to various GBV-C/HGV markers in eastern Taiwan aborigines. METHODS: We used RT-PCR and anti-HGenv u-plate to investigate the prevalence of GBV-C/HGV in eastern Taiwan aborigines. We also used ELISA, dot blot assay, and Western blot to detect the serologic responses to various GBV-C/HGV markers. RESULTS: The prevalence of GBV-C/HGV RNA in the general population of eastern Taiwan aborigines is about 5% (17/317), while 14% (43/317) have anti-E2 antibodies. There were no significant differences in antibody titer against one consensus core peptide (PPSSAAACSRGSPR) between GBV-C/HGV RNA-positive and -negative sera. Only 23 of 42 serum samples positive in the anti-HGenv u-plate EIA assay were positive (55%) in the dot blot assay. No positive signal was detected by Western blot using either recombinant NS3 or commercial E2 proteins. CONCLUSIONS: Antibodies against one consensus core peptide (PPSSAAACSRGSPR) may not constitute a good marker for the detection of GBV-C/HGV viremia. For the detection of anti-E2 antibodies, the anti-HGenv u-plate assay is more sensitive than the dot blot assay. Western blot assay is not a sensitive method for detecting GBV-C/HGV infection.     

Clinical implications of GBV-C/HGV infection in patients with “HCV-related” chronic hepatitis

Background/Aims: To evaluate the clinical, biochemical and histological implications of a concomitant HGV infection in “HCV-related” chronic liver disease.Methods: Eighty-three HCV-RNA positive patients with chronic liver disease were tested for GBV-C/HGV coinfection by heminested PCR.Results: Twenty-two (26.5%) patients were found to be positive for GBV-C/HGV RNA. GBV-C/HGV + patients differed significantly from GBV-C/HGV − ones for younger age, higher frequency of history of drug addition, which in turn might favor coinfection with interferon-sensitive HCV genotypes (3a), and increased probability of long-term response to interferon. GBV-C/HGV infection appears to have no responsibility for specific aspects of HCV infection such as biochemical or histological cholestatic features, lymphoid follicles, symptomatic cryoglobulinemia or presence of serum autoantibodies, including LKM₁. It does not worsen the HCV-related disease (ALT levels and histological activity) and does not significantly interfere with HCV infection, as explored by the number of hepatocyles positive for HCV antigens. The amount of steatosis (mean score) was shown to be higher in GBV-C/HGV + patients. A virological follow up was performed in 17 interferon-treated GBV-C/HGV + patients On the whole, GBV-C/HGV seems to be as sensitive to IFN treatment as HCV, but recurrence after withdrawal is more frequent. In spite of this, ALT levels often remain normal after treatment withdrawal.Conclusions: The present data suggest that GBV-C/HGV infection, apart from more marked liver steatosis, does not modify the overall picture of chronic hepatitis due to HCV infection.     

Seroprevalence, Viremia and Genotype Distribution of Hepatitis C Virus: A Community-Based Population Study in Northern Italy

Background: Our aim was to define the burden of HCV infection and the related risk factors in a sample of the general population of northern Italy Materials and Methods: This is a survey on the prevalence of hepatitis C virus (HCV) infection carried out in a cohort (861 males and 1,293 females aged 17–67 years) from the general population of northern Italy. Results: The crude HCV seroprevalence rate was 3.3%, higher in females than in males (p < 0.01) and with a clear age-related effect (test for linear trend: p < 0.01). When adjusted for sex and age in relation to the reference population, the prevalence was 3.7% )95% CI: 2.9–4.5%). In the univariate analysis, HCV infection was related to intravenous drug use (IVDU) (p < 0.001); transfusion (p < 0.001); tattooing (p = 0.02); chiropodist/manicure (p < 0.001); number of children (p < 0.01); educational level (p < 0.001). In the multivariate analysis sex, age over 50 years, transfusion, IVDU and tattooing were confirmed as risk factors, while the educational level seems to be a protective factors. Separate multivariate analysis for males and females points out that the age shift, the protective effect of education and the number of children as risk factor were present only in females. HCV viremia was detected in the 71.8% of the seropositive, resulting in an infection rate of 2.4% (95% CI: 1.7–3.0%). Genotype 1b accounted for 64.7% of isolates. Conclusion: In the general population of our area, HCV infection is mesoendemic and current infections are mostly sustained by genotype 1b. Received: November 29, 2000 · Revision accepted: October 7, 2001     

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/GBV-C in liver tissue and in sera from patients with chronic hepatitis C

Summary  Forty-eight persons (M=45, F=3; age range=20–53, mean=32.2) affected with chronic hepatitis C were tested for HGV/GBV-C RNA and HCV-RNA by nested PCR and DEIA in serum and in liver specimens to evaluate the prevalence and the impact of HGV/GBV-C coinfection in patients with chronic HCV-related hepatitis. Sera were also assayed for antibodies to HGV/GBV-C E2 protein. Serum HGV/GBV-RNA could be detected in nine (19%) patients, and anti-E2 antibodies in 22 (46%) patients. The presence of HGV/GBV-C RNA or anti-E2 antibodies was mutually exclusive. The cumulative prevalence of HGV/GBV-C infection was 65% (31/48); the majority of these patients (26/31, 84%) were intravenous drug users (IVDUs). In eight of nine patients viraemic for HGV/GBV-C, RNA positivity could be revealed even in liver specimens; these eight patients were also positive for HCV-RNA both in serum and the liver and did not exibit any specific association with HCV genotype. HGV/GBV-C RNA negative strand RT-PCR testing was negative in all of the eight liver specimens, providing little support to the hypothesis that liver represents the primary site of HGV/GBV-C replication. Moreover, patients with HGV/GBV-C and HCV coinfection were comparable to those with HCV infection alone in terms of biochemistry and liver histology.     

GB virus C/Hepatitis G virus infection is frequent in American children and young adults.

The novel flavivirus GB virus C/hepatitis G virus (GBV-C/HGV) has been detected in approximately 2% of blood donors in the United States, and neutralizing antibody to the envelope protein (E2), a marker of previous infection with GBV-C/HGV, is present in approximately 9% of donors. The rate of GBV-C/HGV infection among American children is unknown. To determine whether viral infection might occur during childhood, 160 serum specimens (obtained from blood bank samples) from children and young adults with no history of transfusion were tested. Viral RNA and antibody to E2 were detected in 6.3% and 9.4% of subjects, respectively. Evidence of previous or current infection (viremia and/or antibody to E2) was detected in 13.8% of subjects, indicating that GBV-C/HGV infection appears to be common among American children and young adults, even in the absence of blood transfusion.     

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.     

Lower Hepatitis G Virus Infection Prevalence Compared to Hepatitis B and C Virus Infection Prevalences

To more accurately determine the seroprevalence of hepatitis G virus (HGV) infection, we surveyed antibody to HGV (anti-E2) by enzyme-linked immunosorbent assay (ELISA) and HGV RNA by nested polymerase chain reaction (PCR) in 298 residents of a hepatitis C virus (HCV)-endemic area of Japan and in 225 hemodialysis patients. We then compared these findings with known HCV and hepatitis B virus (HBV) infection prevalences. Anti-E2 and HGV RNA prevalences were 32 (10.7%) and 5 (1.7%) in the residents and 24 (10.7%) and 10 (4.4%) in the hemodialysis patients, respectively. Anti-E2 and HGV RNA concurrence was found in two of the hemodialysis patients. Total HGV marker (anti-E2 and/or HGV RNA) prevalences [37 (12.4%) in residents and 32 (14.2%) in hemodialysis patients], were significantly lower than the prevalences of antibody to HCV (anti-HCV) by ELISA [59 (19.8%) and 96 (42.7%)], and antibody to hepatitis B core antigen (anti-HBc) by radioimmunoassay (RIA) [87 (29.2%) and 101 (44.9%)] (P < 0.05). The anti-HCV prevalence in subjects with total HGV marker was significantly higher than in those without total HGV marker. There was no significant difference in anti-HBc prevalence between those with and without total HGV marker. The viremic rate was highest in HCV infection (HCV RNA by PCR/anti-HCV) (83.2%), with HGV infection (HGV RNA/total HGV marker) (21.7%) intermediate, and HBV infection (hepatitis B surface antigen by RIA/anti-HBc) (5.3%) lowest (P < 0.05). These findings indicate that HGV infection was less endemic than HCV and HBV. HGV was eliminated naturally more frequently than HCV infection and less frequently than HBV infection.