Significance of antibodies to the recombinant E2 protein of hepatitis G virus in haemodialysis patients

Patients on maintenance haemodialysis represent a high-risk group for parenterally transmitted viral infections, such as hepatitis B, C and G. In addition to hepatitis G virus (HGV) (GBV-C) RNA, analysed in previous studies, we characterized the seroprevalence rates of antibodies to the putative E2 protein (anti-E2) of HGV in a German cohort of patients on maintenance dialysis ( n = 72) in comparison to healthy blood donors ( n = 100). The presence of anti-E2 and/or HGV RNA as indicators of present or past HGV infection could be demonstrated in 34.7% of patients and in 16% of the blood donors ( P < 0.01). The infection rates with HGV seem to increase only during the first 6 years of haemodialysis. The simultaneous presence of viraemia and anti-E2 was found very rarely in patients and controls. Therefore, the emergence of anti-E2 indicates clearance of HGV viraemia. In conclusion, patients on haemodialysis are at high risk of acquiring HGV infection, but a chronic carrier state with viraemia is rare. The risk of infection is not strictly correlated with the duration of dialysis.     

Fulminant hepatitis and the new G/GBV-C flavivirus

A new virus within the family Flaviviridae, 'hepatitis' G/GBV-C, has been incriminated by several authors as a causative factor of idiopathic or cryptogenic fulminant hepatitis, a syndrome of presumed viral aetiology. Review of worldwide data from 22 studies on 364 cases indicates that G/GBV-C infection is present in approximately 20% of idiopathic cases but a similar or even higher prevalence is detected in fulminant hepatitis of viral B, D or C aetiology, reflecting a high rate of parenteral viral exposure rather than a specific aetiology of fulminant hepatic failure. An aetiopathogenic role of G/GBV-C in fulminant hepatitis seems to be further refuted by the analysis of other data in the literature. The presence of G/GBV-C infection in fulminant hepatic failure is largely a result of secondary infection or coinfection. The aetiopathogenetic mystery of cryptogenic or idiopathic fulminant hepatitis remains unsolved.     

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.     

HGV/GBV-C infection in patients with acute hepatitis of different etiology and in patients with chronic hepatitis C

To investigate the prevalence of hepatitis G virus (HGV/GBV-C) in patients with liver disease and to confirm its hypothesized ability to cause liver damage, we studied 130 subjects; 61 had chronic hepatitis C virus infection and 69 had acute hepatitis of either defined etiology (n = 57) or of unknown origin (n = 12). Positivity for HGV/GBV-C RNA was detected in 10 of the 61 subjects with chronic hepatitis C (16.3%) and in 11 of the 57 subjects with acute hepatitis of defined etiology (19%), whereas we failed to detect HGV/GBV-C viremia in subjects with hepatitis of non-established etiology. Patients exhibiting positivity for HGV/GBV-C RNA were found to be comparable to those exhibiting negativity for HGV/GBV-C RNA in terms of both liver function tests and Knodell's score (in liver biopsies); the affect of HGV/GBV-C infection on the biohumoral and histological activity in patients with chronic hepatitis C therefore appears to be minimal or absent. Similar clinical features were observed in patients with acute hepatitis of known etiology whether they were positive or negative for HGV/GBV-C RNA. However, long-term clinical studies are still required to clarify the actual impact of HGV/GBV-C co-infection. In our geographic, i.e., a region or north-east Italy, HGV/GBV-C infection appears to be strictly related to intravenous drug use, and this agent does not seem to be responsible for acute hepatitis of unknown etiology; other etiological agents are probably involved. Received Feb. 17, 1997; accepted June 27, 1997     

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 C virus quasispecies in the natural course of HCV-related disease in patients with haemophilia

Patients with haemophilia show high prevalence of hepatitis C infection but low rate of progressive liver disease when they are not co-infected with HIV. The balance between host immune system and hepatitis C virus (HCV) variability seems to play a major role in the evolution of the HCV-related disease. To address this point we have studied, in a group of selected patients with haemophilia, the composition and in some cases the evolution, of the highest variable envelope gene within the hypervariable region 1 (HVR1) of the HCV, which is the region more directly exposed to the host immune response. Five of 12 patients show a very high homogeneity of the HVR1 and four of those had severe progressive liver disease. These results seem to confirm the major role of the immunity in driving the variability of the HCV rather than the high degree of different HCV strains to which haemophiliacs have been in touch with, during their long-term replacement therapy. Our results seem in keeping with other studies on different type of patients, where a low degree of quasispecies variability has been demonstrated in relationship with the progression and the severity of their liver disease.     

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.     

Antibodies to the E2 Protein of GB Virus C/Hepatitis G Virus: Prevalence and Risk Factors in Different Populations in Italy

Background: Many aspects of the epidemiology of GB virus C/hepatitis G virus (GBV-C) infection have not been fully elucidated. The purpose of this study was to assess the prevalence of GBV-C antibodies and risk factors in different subjects living in Italy. Materials and Methods: A total of 1,005 sera were tested for the presence of antibodies to the of GBV-C E2 protein using a recently developed enzyme immunoassay. Results: A high prevalence of GBV-C antibodies was found in healthy blood donors (12.6%). Hemodialysis patients and drug users showed higher rates of GBV-C seropositivity (22% and 39%, respectively). Immigrants from sub-Saharan Africa and South Asia had anti-GBV-C prevalence comparable to that found in Italian blood donors, whereas higher and lower rates were detected in immigrants from Latin America and the Caribbean (19.5%) and from Mediterranean Africa (5.6%). Conclusion: GBV-C infections are widespread in the general population in Italy and particularly common in risk groups. The different prevalence of GBV-C antibodies detected in third world immigrants is likely to reflect the prevalence in the countries of origin. However, the observation that the length of residency in Italy is a significant risk factor may suggest that at least some GBV-C infections are contracted in Italy. Received: July 31, 2000 · Revision accepted: October 9, 2000     

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.     

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.     

Hepatitis E virus infection may be transmitted through blood transfusions in an endemic area

AIM: To address the issue of whether or not hepatitis E virus (HEV) is transmitted parenterally. METHODS: We conducted a retrospective study which involved 145 multiple transfused patients and 250 healthy controls. A prospective study was also undertaken involving 50 hospitalized patients, 25 of whom were transfused with 107 blood units, while the other 25 did not receive any transfusions. RESULTS: In our retrospective study, markers of acute HEV infection (IgM anti-HEV and HEV RNA) were detected in a significantly higher number of multiple transfused patients (13 of 145) compared to controls (two of 250) (P < 0.001; OR = 12.21 [95% confidence interval: 2.71-54.70]). All 13 HEV-infected patients had been transfused at least once in a 3-month period before testing. Overall, patients positive for any of the HEV markers (IgG, IgM or HEV RNA) had received more blood transfusions, had higher occurrence of icteric disease and higher serum alanine aminotransferase levels. In our prospective study, IgG anti-HEV was detected in 11 of 107 donor samples, three of 25 patients in their pretransfusion samples (one sample was positive for IgM anti-HEV as well) and two of 25 control patients. Post-transfusion HEV infection developed in three of 22 susceptible (IgG anti-HEV negative) transfused patients; the infection was traced to their four respective donors who were asymptomatic, HEV RNA positive (4/4) and IgM anti-HEV positive (3/4). In contrast, none of the non-transfused patients developed HEV infection during the follow-up period. CONCLUSION: Frequent transmission of HEV by blood transfusion places recipients at risk and warrants redefining of the donor screening policy by blood banks, especially in endemic areas.