Hepatitis G Research Articles

Hepatitis G virus infection in Egyptian children with chronic renal failure (single centre study)

BackgroundHepatitis G virus (HGV) is an RNA virus. It is mainly transmitted through exposure to contaminated blood although other routes may also exist. Patients with chronic renal failure (CRF) are at high risk of acquiring HGV because they require frequent blood transfusions. Ongoing HGV infection can be only diagnosed by demonstrating viremia in patient sample by reverse transcriptase (RT) PCR. Antibodies to the envelop protein E2 (anti E2) of HGV is an indicator of virus clearance and testify past HGV contact. This cross sectional study was done to assess the frequency of HGV exposure (ongoing and past infection) in Egyptian children with CRF and to study the possible risk factors of infection.MethodsThis study included 100 children with CRF [34 on regular haemodialysis (HD) and 66 before the start of dialysis (predialysis)]. All patients sera were tested for HGV RNA by RT-PCR, anti E2, hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (HBcAB). Twenty five healthy children of matched age & sex were used as controls.ResultsHGV RNA was positive in 9 (26.5%) of HD and 9 (13.6%) of predialysis children. Anti E2 was positive in 14 (41.2%) of HD and 19 (28.8%) of predialysis children.In comparison to controls; CRF (n = 100); HD and predialysis children had significantly higher prevalence of anti E2 [4% VS 33% for all CRF cases; (p = 0.002)& 41.2% (p = 0.002) and 28.8% (p = 0.01); for HD and predialysis groups; respectively]. HGV RNA was significantly more prevalent only in HD children in comparison to controls (p = 0.03). HD and predialysis children did not have significant difference in the prevalence of HGV RNA (p = 0.16) or anti E2 (p = 0.26).HGV exposure was not correlated with positivity of anti HCV (p = 0.32), HCV RNA (0.09), HBsAg/HBcAB (p = 1), age (p = 0.06), or gender (p = 0.83). It was significantly correlated with duration of the disease (p < 0.001). Ongoing HGV infection was significantly more prevalent with frequent blood transfusion (p < 0.001). There were no significant differences in serum levels of ALT (p = 0.09), total bilirubin (p = 0.1) and albumin (p = 0.06) in children with ongoing infection in comparison to healthy controls.ConclusionsThe frequency of HGV exposure in Egyptian children with CRF appears to be high and is mainly related to frequent blood transfusions and longer disease duration. HGV infection in these children is not associated with significant changes in hepatic biochemical parameters.

HIV-GB virus C co-infection: an overview

GB virus C (GBV-C) and hepatitis G virus (HGV) are two isolates of the same virus, independently identified in humans in the 1990s by two research laboratories, and were initially considered a potential cause of liver disease. Studies failed to associate the virus with hepatitis or any known human disease. GBV-C reappeared in the scientific scene when some research groups, in an attempt to find the interference of the virus among HIV seropositive patients, reported a lower mortality rate and slower disease progression among co-infected patients. From then on, several mechanisms have been proposed to clarify this putative benefit; however, the question whether GBV-C exerts a protective effect in HIV-infected patients remains to be resolved.

Frequency and genotype of GB virus C among Iranian patients infected with HIV

GB virus C (GBV-C) infection is frequent in patients infected with the human immunodeficiency virus (HIV) due to similar transmission routes of these viruses. The aim of this study was to determine the rate of infection and genotypic characteristics of GBV-C in this population. The presence of GBV-C RNA was determined in serum samples of 106 patients infected with HIV by reverse transcriptase-nested polymerase chain reaction. GBV-C genotypes were determined by direct sequencing. Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis C antibody (anti-HCV), alanine aminotransferase (ALT) levels, HIV viral load and CD4(+) count were also tested in all patients. The overall prevalence of GBV-C infection was 11.3% in HIV patients. There was no significant difference between patients with and without GBV-C infection regarding age, sex, route of transmission, viral load, ALT levels, HBV and HCV co-infection and treatment with antiretroviral drugs. 66.7% of patients with GBV-C had a CD4(+) count > or = 200 and 33.3% had a CD4(+) count < 200 cells/mm(3). Phylogenetic analysis revealed that all GBV-C isolates were genotype 2, and classified as subtype 2a. GBV-C infection is relatively common in patients infected with HIV. The prevailing GBV-C genotype 2a in this study group concurred with reports from other parts of the Middle East.

GBV‐C coinfection is negatively correlated to Fas expression and Fas‐mediated apoptosis in HIV‐1 infected patients

Persistent coinfection with the apathogenic GB virus C (GBV-C) is associated with slower disease progression of human immunodeficiency virus (HIV)-1 infection. Aim of this study was to investigate whether Fas plays a role in this beneficial effect. Fas expression and susceptibility to Fas-mediated apoptosis (FMA) was analyzed in peripheral blood mononuclear cells (PBMCs) of HIV-1 patients coinfected and non-coinfected with GBV-C. Fas expression and function was evaluated in 42 GBV-C coinfected and 101 non-coinfected HIV-1 patients. Thirteen healthy and 11 Hepatitis C virus (HCV)-monoinfected individuals were analyzed as controls. Cell surface Fas expression was determined by flow cytometric analysis. Apoptosis was evaluated by staining with Annexin V and Viaprobe followed by multiparameter flow cytometry analysis. In untreated HIV-1 patients GBV-C coinfection was associated with significantly lower percentage of Fas expressing cells as compared to GBV-C non-coinfected individuals. Expression of Fas was directly correlated with sensitivity to Fas-mediated apoptosis. Sensitivity to FMA was unchanged in GBV-C coinfected patients. PBMCs of patients receiving highly active antiretroviral therapy (HAART) did not show such a difference. Untreated HIV-1 patients with GBV-C coinfection have reduced cell surface Fas expression. Lower FMA of T-cells might contribute to prolonged survival of GBV-C coinfected HIV-1 patients.

Clinicopathological features and natural history of acute sporadic non‐(A‐E) hepatitis

The aim of the present study was to describe the clinicopathological characteristics and the natural history of acute non-(A-E) hepatitis and to assess the possible role of hepatitis G virus (HGV), TT virus (TTV) and mainly SEN virus (SENV). A cohort of 55 patients with sporadic acute non-(A-E) hepatitis with a mean follow up of 31 (6-55) months was studied. The clinical presentation was fulminant in one (1.8%), protracted with impaired regeneration in seven (12.7%) and benign in the remaining 47 (85.5%) cases. Progression to chronic hepatitis was observed in 15 (27.3%) patients; it was more frequent in clinically severe than in non-severe cases (five of eight patients or 62.5% vs 10 of 47 patients or 21.3%, P = 0.028). Six of 10 biopsied chronic non-(A-E) cases developed cirrhosis within 10-33 months. Serum HGV-RNA was detected in 16 of 55 (29.1%) patients, TTV in 20 of 38 (52.6%) patients and SENV-D/H DNA in 20 of 55 (36.4%) cases. HGV-RNA was detected more frequently in clinically severe than in non-severe cases (five of eight or 62.5% vs 11 of 47 or 23.4%, P = 0.038). There was no other association between the presence of HGV, TTV, or SENV infection and patient characteristics or severity and outcome of disease. HGV, TTV, and SENV do not seem to be responsible for the majority of sporadic acute non-(A-E) hepatitis cases. Our cohort further supports the existence of new, unknown hepatitis agent(s) with uncertain mode of transmission. The non-(A-E) agent(s) can also cause chronic hepatitis, which often has an aggressive course with rapid development of cirrhosis.

Reduced Mother‐to‐Child Transmission of HIV Associated with Infant but not Maternal GB Virus C Infection

Prolonged coinfection with GB virus C (GBV-C) has been associated with improved survival in human immunodeficiency virus (HIV)-infected adults. We investigated whether maternal or infant GBV-C infection was associated with mother-to-child transmission (MTCT) of HIV-1 infection. The study population included 1364 HIV-infected pregnant women enrolled in 3 studies of MTCT of HIV in Bangkok, Thailand (the studies were conducted from 1992-1994, 1996-1997, and 1999-2004, respectively). We tested plasma collected from pregnant women at delivery for GBV-C RNA, GBV-C antibody, and GBV-C viral genotype. If GBV-C RNA was detected in the maternal samples, the 4- or 6-month infant sample was tested for GBV-C RNA. The rates of MTCT of HIV among GBV-C-infected women and infants were compared with the rates among women and infants without GBV-C infection. The prevalence of GBV-C RNA in maternal samples was 19%. Of 245 women who were GBV-C RNA positive, 101 (41%) transmitted GBV-C to their infants. Of 101 infants who were GBV-C RNA positive, 2 (2%) were infected with HIV, compared with 162 (13%) of 1232 infants who were GBV-C RNA negative (odds ratio [OR] adjusted for study, 0.13 [95% confidence interval {CI}, 0.03-0.54]). This association remained after adjustment for maternal HIV viral load, receipt of antiretroviral prophylaxis, CD4(+) count, and other covariates. MTCT of HIV was not associated with the presence of GBV-C RNA (adjusted OR [aOR], 0.94 [95% CI, 0.62-1.42]) or GBV-C antibody (aOR, 0.90 [95% CI, 0.54-1.50]) in maternal samples. Reduced MTCT of HIV was significantly associated with infant acquisition of GBV-C but not with maternal GBV-C infection. The mechanism for this association remains unknown.

Activation of Interferon Response Genes and of Plasmacytoid Dendritic Cells in HIV-1 Positive Subjects with GB Virus C Co-Infection

GB virus C (GBV-C) coinfection has a protective role in Human Immunodeficiency Virus (HIV) infection, and increases the duration of suppression of HIV-1 viremia in patients under Highly Active Anti-Retroviral Therapy (HAART). Since innate antiviral response may be involved in the protection, we analyzed the possible role of GBV-C as activator of innate immunity. To this aim, we measured the extent of activation of the interferon (IFN) system and of circulating Dendritic Cells (DC) in vivo, and the ability of GBV-C to activate these functions in vitro. Activation of IFN system and of circulating DC was compared in GBV-positive and -negative HIV-1 co-infected patients with HAART-driven suppression of HIV-1 viremia. Endogenous levels of IFN-gamma and RNA-dependent protein kinase (PKR) mRNA were significantly higher in peripheral blood mononuclear cells (PBMC) from GBV-C-positive when compared to GBV-C-negative patients. IFN-gamma expression was correlated with all the Interferon response genes (IRGs) and with GBV-C viremia. The frequency of circulating plasmacytoid DC (pDC) expressing the CD80 activation marker was increased in GBV-C-positive patients, and was correlated with GBV-C viral load. In vitro experiments indicated that GBV-C is able to induce IFN-gamma expression in PBMC. In addition, in PBMC cultures GBV-C induced an increase of CD80 expression by pDC, that was reduced by antibody to IFN-gamma. Our data indicate that in HIV-positive patients GBV-C coinfection promotes the activation of IFN-gamma and downstream IRG expression, as well as with the activation/maturation of circulating pDC. GBV-C-driven IFN-gamma activation is, at least in part, responsible for the increased maturation of pDC. This crosstalk may suggest a role for GBV-C coinfection in boosting the innate antiviral response to HIV infection.

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.

The prevalence of GB virus C/hepatitis G virus RNA among healthy and HCV-infected Catalan children

GB virus C (GBV-C) is a blood-borne flavivirus. The prevalence of GBV-C viremia among healthy adults is 0.5% to 4% and, to date, no disease has been definitely associated with GBV-C infection. We conducted a cross-sectional study to evaluate GBV-C viremia prevalence in a group of 327 healthy children with normal alanine amino transferase (ALT) levels (Group A) and elevated ALT levels (Group B) of unknown origin, and among 38 pediatric patients with mother-to-child-transmitted hepatitis C virus (HCV) infection (Group C). No statistically significant differences were observed between prevalences in Groups A and B (2.2% vs 6.7%, p = 0.06). None of the children in Groups A or B who tested positive for GBV-C RNA showed any clinical symptoms. The prevalence of GBV-C viremia in Group A was lower than for patients in Group C (2.2% vs 13.2%, p = 0.007); no differences were observed in HCV infection characteristics between those patients who were co-infected with GBV-C and those who were not. In conclusion, while GBV-C viremia is more frequent among HCV-infected pediatric patients, it is neither associated with liver disease nor has any influence on HCV-related chronic hepatitis.

Hepatitis-G Virus Infection in Multi-transfused Patients and Intravenous Drug Abusers: New Delhi Experience

Hepatitis G virus (HGV) is a newly described virus that has been implicated in transfusion-associated hepatitis. HGV-RNA indicating current infection has frequently been isolated from the sera of multi-transfused patients (MTPs) and that of intravenous drug abusers (IVDAs). There is insufficient data on its prevalence among these high-risk groups in India. Hence this study was designed to evaluate the prevalence of HGV infection in MTPs and IVDAs. A total of 90 (57 males and 33 females) MTPs and 65 (44 males and 21 females) IVDAs were recruited in the study. Patients' sera were tested for liver function profile, HGV-RNA, anti-HCV, HCV-RNA, HBsAg, and HBV-DNA. HGV-RNA was detected in 17.7% (16/90) MTPs and 23% (15/65) IVDAs, and 93.5% of our HGV-positive patients were found to be co-infected with either HBV (38.7%) or HCV (74.1%). The sero-prevalence of HBV was found out to be 40% and 21.5%, respectively, in the two groups, that of HCV was 32.2% and 32.3%, respectively, and dual infection was observed in 15.5% and 10.7% of the subjects, respectively. There were no statistically significant differences between the clinical, biochemical, and serological profiles of HGV-positive and negative patients. The prevalence of HGV infection in these high-risk groups is significantly higher than in controls. HGV is found to be co-infected more frequently with HCV than with HBV.

Hepatitis G Virus Exposure in Dialysis Staff

Hepatitis G virus (HGV) is a blood-borne virus. Some present data demonstrate an occupational risk of HGV infection in medical staff of dialysis units. The aim of this investigation was to assess the prevalence of HGV exposure in dialysis staff. This study was performed in a main dialysis unit in Iran. In 27 dialysis staff, HGV exposure was detected serologically by the presence of anti HGV envelope protein E2 (anti-E2) by an enzyme-linked immunosorbent assay, and compared with 77 hemodialysis (HD) and 13 continuous ambulatory peritoneal dialysis (CAPD) patients. All of them were also screened for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis C antibody (anti-HCV). A low prevalence of HGV exposure was found in the dialysis staff (0%), which nearly corresponded to the prevalence of the dialysis patients (HD 3.89%, CAPD 0%). The prevalence of anti-HCV and anti-HBs in staff was 37.03% and 33.33%, respectively, which was higher than HGV anti-E2. The prevalence of HGV exposure was low in dialysis staff in our study, and was near to the prevalence of HGV exposure in dialysis patients. Therefore, it can be concluded that the occupational risk for HGV exposure in our investigation was minimal.

Hepatitis G virus exposure in dialysis patients

Hepatitis G virus (HGV) is a blood-borne virus. The predominant route of its transmission is parenteral. The aim of this study was to assess the frequency of HGV exposure in haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients in Iran. This study was performed in a major dialysis centre in Tehran, Iran. The study cohort consisted of 77 patients on HD and 13 patients on CAPD. The presence of anti-HGV envelope protein E2 (anti-E2) in the blood serum, as determined by means of an ELISA assay, indicated HGV exposure. All patients were also screened for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs) and hepatitis C antibody (anti-HCV). In patients who tested positive for anti-E2, HGV RNA was detected by RT-PCR using primers derived from the NS5A region of the viral genome. In total, 3.89% of the HD patients and none of the CAPD patients tested positive for anti-E2. None of the patients tested positive for HGV RNA. The mean age of the anti-E2-positive patients was 53.3 +/- 26.5 years, with 66.66% having previously received blood transfusion. The mean duration of dialysis of the anti-E2-positive patients was 68 +/- 64 months. Co-infection with HCV or HBV was not observed in the anti-E2 positive patients. The rate of exposure to HGV was low among the dialysis patients in our study. The appearance of anti-E2 was accompanied by clearance of serum HGV-RNA. No relationship was noted between HGV exposure and age, sex, history of blood transfusion, time on dialysis and HCV or HBV markers.

Evaluation of Circulating Natural Type 1 Interferon-producing Cells in HIV/GBV-C and HIV/HCV Coinfected Patients: A Preliminary Study

GB virus-C (GBV-C) is a flavivirus that probably influences HIV infection-associated disease among HIV/GBV-C coinfected patients and inhibits the progression of HIV infection to AIDS. To address the possibility of immune-modulating effects of GBV-C coinfection in HIV patients, we evaluated interferon-producing cells in HIV/GBV-C coinfected patients and compared them to HIV-infected patients. We performed a pilot study to enumerate interferon-producing cell count by two-color flow cytometric analysis and also for determining the frequency of ongoing GBV-C and HCV infection among patients infected with HIV. Then, 83 asymptomatic HIV-positive patients were considered for evaluation of interferon-producing cells. Eighty three patients were stratified in four groups according to the HCV and GBV-C infection status: patients infected with HCV and GBV-C (GBV-C+/HCV+), patients infected with GBV-C but not with HCV (GBV-C+/HCV-), patients infected with HCV but not with GBV-C (GBV-C-/HCV+), and patients not infected by GBV-C and HCV (GBV-C-/HCV-). GBV-C was detected in plasma samples from 15.5% of HIV-infected patients and the frequency of HCV infection was 47.5%. Interferon-producing cells in GBV-C coinfected individuals revealed a wider range of numbers; however, there was no significant difference in the interferon-producing cell count among HIV-infected individuals. It does not appear that GBV-C coinfection affects generation or redistribution of interferon-producing cells in HIV-infected patients with relatively intact immune system.

Hepatitis G Virus Infection in Patients with Hepatocellular Carcinoma in Recife, Brazil

The evidence of a higher incidence of hepatitis G virus (HGV) infection among patients with hepatocellular carcinoma (HCC) and the relatively high prevalence of patients with primary liver carcinoma without apparent risk factors in our country motivated the present study, the objective of which was to determine the frequency of HGV-ribonucleic acid (RNA) in a series of patients with HCC. The diagnosis of HCC was established based on alpha-fetoprotein levels (>400 ng/ml), a compatible image and/or biopsy of the hepatic nodules. Markers of hepatitis B virus (HBV) (HBsAg and anti-HBc), hepatitis C virus (HCV) (anti-HCV) and HGV (HGV-RNA) were investigated using MEIA and RT-PCR (reverse transcriptase polymerase chain reaction). There were 32 patients evaluated, including 20 males (63%), with a mean age of 58 years. Twenty-eight (88%) patients were cirrhotic (Child-Pugh: A = 8 patients, B = 14, and C = 6) and 50% reported alcohol consumption. Serological hepatitis markers were detected in 26 (81%) patients, including HBV in 19 (59%), HCV in 12 (38%) and HGV in 9 (28%). Only one (3%) patient was positive for HGV alone. The prevalence of HGV in blood donors from the same region is 10%. The findings suggest that, despite the frequent detection of HGV markers in patients with HCC, isolated infection with this agent does not seem to be a relevant factor in the etiology of this carcinoma.

Enhanced and resumed GB virus C replication in HIV-1-infected individuals receiving HAART

In patients co-infected with HIV-1 and GB virus C (GBV-C), the disappearance of GBV-C RNA has been associated with accelerated disease progression. We studied longitudinal GBV-C viral titres in 28 HIV-1/GVB-C co-infected individuals receiving HAART. During HAART, median GBV-C RNA titres increased from 95 to 6000 copies/ml (P < 0.001). In patients interrupting HAART, GBV-C-RNA titres decreased as HIV replication resumed. These findings further support the theory that GBV-C replication could depend on the dynamics of HIV progression.

Detection of hepatitis G virus envelope protein E2 antibody in blood donors

The frequency of hepatitis G virus exposure in blood donors varies between 2.5% in Japan to 24.2% in Poland. Therefore there is a geographic difference in distribution of hepatitis G virus (HGV) in the world. We aimed to determine the frequency of HGV exposure in Iranian blood donors. Blood samples from 478 Iranian volunteer blood donors were tested. Positive anti-E2 samples were tested for HGV RNA by reverse transcriptase polymerase chain reaction (RT PCR) using primers derived from the NS5A region of the viral genome. Of the 478 donors enrolled in our study, five (1%) were positive for anti-E2. Only one donor out of a total of three HBsAg-positive donors was co-infected with HGV, but we did not find HGV and HCV co-infection in our subjects. HGV RNA was not observed in the five anti-E2-positive subjects. We did not find HGV viremia and antibody at the same time. A low frequency of HGV exposure in blood donors was found in this study. We did not observe co-infection of HGV with HCV in our subjects, supporting the theory that although the parenteral route is the most effective means of transmission, other routes such as sexual contact and intra-familial contact may also play a role in HGV transmission.

Effect of GB virus C co-infection on response to generic HAART in African patients with HIV-1 clade C infection

In 38 African AIDS patients initiating generic HAART, GB virus C (GBV-C) RNA-positive patients retained GBV-C viraemia during 52 weeks of HAART, had a faster decline in HIV viral load (P = 0.03), fewer opportunistic infections (14.3 versus 50%, P = 0.18), and suffered no serious adverse events (none versus 61%, P = 0.008) compared with patients without GBV-C. GBV-C co-infection may be associated with a beneficial effect on African AIDS patients treated with generic HAART.

The GBV-C envelope glycoprotein E2 does not interact specifically with CD81

The addition of GB virus C (GBV-C) E2 protein to cells inhibits HIV replication in vitro, presumably triggered by interactions with a specific cellular receptor. Indirect evidence suggests that CD81 is the GBV-C E2 cellular receptor. We found that E2 binding to cells was not dependent upon human CD81, and that soluble CD81 did not compete with GBV-C E2 for cell binding. GBV-C E2 protein thus does not appear to interact with CD81.

Association between active GB virus-C (hepatitis G) infection and HIV-1 disease in Uganda

Although not linked to a disease, GB virus-C viraemia has been associated with an improved prognosis in HIV-1-co-infected individuals. Most studies have been conducted on men (men who have sex with men or injection drug users) infected with HIV-1 subtype B, whereas here we report on both male and female subjects from rural Uganda, predominantly infected via the heterosexual route with HIV-1 subtypes A and D. In a longitudinal study of 272 participants, 47 were GBV-C positive and 181 negative, as determined by reverse transcription-polymerase chain reaction, in both of two plasma samples taken a median of 5.0 years apart. The remainder either acquired (25) or cleared (19) infection. Multilevel regression analyses and Cox survival analyses revealed that participants chronically infected with GBV-C had a slower decline in CD4(+) T cells (P<0.001) and increased survival time (P=0.041) compared with GBV-C RNA-negative, HIV-positive adults. We show that the association between active GBV-C co-infection and improved survival of HIV-1-infected adults is not restricted to HIV subtype B, but is also observed in both males and females infected with HIV subtypes A and D.

HIV entry inhibition by the envelope 2 glycoprotein of GB virus C

Epidemiological studies have revealed an association between GB virus C (GBV-C) long-term viraemia and ameliorated HIV disease progression. We have provided evidence that a single protein of GBV-C, the glycoprotein E2, interferes with early HIV replication steps of both X4- and R5-tropic HIV strains. Preincubation with anti-E2 antibody specifically abrogates the inhibitory effect. Results were confirmed by the in-vitro expression of GBV-C E1/E2 encoding RNA.