Hepatitis G virus infection in hemodialysis patients and the effects of interferon treatment

OBJECTIVE: To characterize the nature of hepatitis G virus (HGV) infections in hemodialysis patients and to determine the responsiveness of HGV to antiviral therapy in these patients. METHODS: HGV, a recently identified flavivirus, is associated with non-A-E viral hepatitis infections. We studied HGV infections in hepatitis C virus (HCV)-infected hemodialysis patients over a 1-yr period, using two independent PCR assays and nucleic acid sequencing. Thirty-four of 63 study patients were treated with interferon. RESULTS: We observed a 27% prevalence (17/63 patients) and a 4% annual incidence of HGV infections in the study population. HGV was not detected in any of the 10 HGV-infected patients immediately after interferon therapy. Although seven of these 10 patients developed HGV relapses, three had long-term responses. The interferon responsiveness of HGV and HCV appeared to be unrelated. In contrast, all seven untreated HGV-infected patients remained viremic. Sequence analyses of the different HGV isolates revealed only very limited genetic variability in the polymerase chain reaction-amplified regions of HGV during 1 yr of observation. CONCLUSIONS: Our data suggest that HCV-infected hemodialysis patients are at substantial risk of acquiring HGV infection and that HGV infections are prevalent in this population. In addition, HGV infections become chronic but are responsive to interferon treatment.     

Antenatal diagnosis of esophageal atresia with tracheoesophageal fistula

We have studied the antibody response to hepatitis B vaccine in 42 hemodialysis patients; 8 of them were diagnosed as having HCV infection before vaccination. Hemodialysis patients received four doses of recombinant HB vaccine (Engerix-B, SKB, 40 micrograms per dose). Seroconversion occurred in 71.4% of all hemodialysis patients; in 79.4% of HCV-negative and in 37.5% of HCV-positive patients. Effective immunity (anti-HBs titer higher than 100 m IU/ml) was observed in 12.5% of HCV positive and in 35.3% of HCV-negative patients. We conclude that HCV infection may modify or postpone the response to hepatitis B vaccine.     

Infection with hepatitis G virus among recipients of plasma products

BACKGROUND: Hepatitis G virus (HGV or GBV-C) is a newly discovered human flavivirus distantly related to hepatitis C virus (HCV). Little information is available on its natural history or routes of transmission, although it can be transmitted parenterally. We investigated the prevalence of persistent infection of HGV and HCV in patients exposed to non-virus-inactivated pooled blood products associated with transmission of HCV. METHODS: RNA was extracted from the plasma of 112 patients with haemophilia and 57 with hypogammaglobulinaemia, as well as from 64 different batches of archived coagulation-factor concentrates and immunoglobulins. RNA was reverse transcribed and amplified with primers from the 5' non-coding region of HCV and HGV by a nested polymerase chain reaction (PCR). Viral RNA was quantified by titration of complementary DNA before amplification. FINDINGS: Among non-renumerated UK blood donors HGV infection (detected by PCR) was more common than HCV infection (four [3.2%] of 125 compared with 137 [0.076%] of 180658 in southeast Scotland). Testing of batches of factor VIII and factor IX concentrates prepared without viral inactivation procedures showed high frequencies of contamination with HGV (16 of 17 factor VIII batches positive; six of six factor IX batches positive), with no difference between renumerated and non-renumerated donors. However, among 95 haemophiliacs who had received non-virus-inactivated concentrates, 13 (14%) were positive for HGV compared with 79 (83%) who were positive for HCV. Two of 37 recipients of long-term immunoglobulin replacement therapy were positive for HGV. Virus inactivation of blood products substantially reduced or eliminated contamination by HGV RNA sequences. INTERPRETATION: Despite the extremely high level of HGV contamination of non-virus-inactivated blood products, their use was not associated with high rates of persistent infection in recipients. The infectivity of HGV in blood products may be lower than that of HCV, or the virus may be less able to establish persistent infection in humans. Whatever the case, the high prevalence of active HGV infection in the general population remains difficult to explain.     

Natural course of HGV infection in haemophiliacs

The natural course of hepatitis G virus (HGV) infection was clarified in 70 haemophiliacs by testing for HGV RNA and antibodies against HGV envelope protein (anti-E2). None of 12 patients treated with only virus-inactivated coagulation factors were infected with HGV. Of 58 patients who received non-inactivated products, 28 (48%) were positive for HGV RNA and/or anti-E2. Of 16 patients with anti-E2, 14 were negative for the viral RNA, and had recovered from HGV infections. HCV antibodies were detected in 59 patients, and eight patients were successively negative for HCV RNA. Thus, the recovery rate of HGV infection (14/28, 50%) was higher than that of HCV (8/59, 14%) (P<0.001). Longitudinal study revealed that anti-E2 developed either during viraemia or some years after seronegativity for HGV RNA. Hence the antibody response itself seemed not to play a major role in the clearance of HGV though anti-E2 was associated with the clearance of HGV RNA. In conclusion, HGV and HCV are prevalent in patients treated with unsterilized coagulation factor concentrates. However, in contrast to HCV, spontaneous recovery is frequently observed in HGV infections.     

Hepatitis G virus co-infection in liver transplantation recipients with chronic hepatitis C and nonviral chronic liver disease

Hepatitis G virus (HGV) is a newly described RNA virus that is parenterally transmitted and has been found frequently in patients with chronic hepatitis C infection. To determine the impact of hepatitis G virus co-infection on morbidity and mortality following liver transplantation, we measured HGV RNA by polymerase chain reaction in pre and posttransplantation sera from a cohort of patients transplanted for chronic hepatitis C and a control group of patients transplanted for nonviral causes who were negative for hepatitis C virus (HCV) RNA in serum. The overall prevalence rate of HGV RNA in transplanted patients with chronic hepatitis C was 20.7%. HGV infection was present before transplantation in 13% while it appeared to have been acquired at the time of transplantation in 7.4%. Mean serum alanine aminotransferase activity, hepatic histological activity, and patient and graft survival were similar between HGV-positive and HGV-negative patients. The prevalence rate of HGV RNA in transplanted controls was 64% (P < .01) with a significantly higher rate of acquisition of HGV infection following transplantation (53%, P < .001) when compared with patients with chronic hepatitis C. Mean serum alanine aminotransferase activity was significantly lower in the control patients with HGV infection alone following transplantation than in patients co-infected with hepatitis C (37 +/- 9 vs. 70 +/- 33 U/L, P < .01). Thus, HGV is frequently found in transplantation patients co-infected with hepatitis C although it appears to have minimal clinical impact. In patients transplanted for nonviral causes of end-stage liver disease, a high rate of hepatitis G acquisition at the time of transplantation may occur but does not appear to predispose to chronic hepatitis.     

High prevalence of anti-HGV/E2 antibodies in HCV-positive patients with non Hodgkin's lymphoma

We evaluated in a series of 33 HCV positive (both RT-PCR and HCV RIBA 2 assays) B cell non-Hodgkin's lymphomas (NHL) patients the prevalence of active and inactive HGV infection by HGV RNA assays (RT-PCR) and anti HGV antibodies directed against E2 structural protein (immunoenzimatic method), a reliable serologic marker of past HGV infection followed by viral clearance. We found only one patient with HGV positivity at RT-PCR (3%). Twenty-six of 33 patients were positive for anti HGV/E2 antibodies (78.8%) suggesting past infection. If confirmed, our preliminary data seem to suggest a higher incidence of HGV past infection in our group of HCV positive patients with B cell NHL.     

Chronic hepatic porphyria and hepatitis B and C virus infections

BACKGROUND: It is known that in patients with porphyria cutanea tarda (PCT) there is an increased prevalence of the hepatitis B virus (HBV) and the hepatitis C virus (HCV). The incidence of anti-HCV in PCT in our country is 21.7% in estimations by the second generation method, however, the incidence of HBV in PCT was not assessed so far. METHODS AND RESULTS: In 60 patients with PCT antigens and antibodies against HBV and HCV were assessed (by the anti-HCV third generation ELISA method) and in subjects with signs of HBV or HCV. HBV DNA and HCV RNA were assessed by the method of the polymerase chain reaction. PCT without detectable HBV or HCV infection was found in 45 subjects (68%). HBV infection only was confirmed in seven subjects (10.6%), however none of the patients had positive HBsAg in serum. All had only antibodies against HBV. HCV infection only was detected in seven patients (10.6%) and HBV and HCV co-infection also in seven patients (10.6%). In the group of patients with HBV and HCV co-infection there was not a single HBsAg positive subject. The mean ALT serum activity was significantly higher as compared with subjects with HBV or HCV infection only (p < 0.05) and the histological finding on liver biopsy was more serious. CONCLUSION: HBV (21%) and HCV (21%) infection participates significantly in the clinical picture of PCT. A special subgroup is formed by patients with PCT and HBV and HCV co-infection who have as a rule a higher ALT activity and more severe histological changes in the liver. The incidence of HBV and HCV infection in PCT in the Czech Republic is double as compared with Germany or Great Britain.     

Liver transplantation in hepatitis C. A Spanish multi-centre experience

OBJECTIVE: The purpose of this retrospective survey was to determine the prevalence and outcome of hepatitis C virus (HCV) infection in cirrhotic patients undergoing liver transplantation (OLT) in Spain in 1992. METHODS: Post-OLT HCV infection was defined by anti-HCV (second-generation ELISA) and/or PCR. Patients were divided into groups A (HCV-positive pre-OLT: n = 124, 46%) and B (HCV-negative pre-OLT: n = 145, 54%). RESULTS: HCV infection was more prevalent in patients originally diagnosed as having non-A non-B cirrhosis (97%) and cryptogenic cirrhosis (79%) than in patients with cholestatic or metabolic diseases. Group A patients were older (53.3+/-7.9 versus 47.6+/-9.7; P< 0.05) and had a higher prevalence of hepatocellular carcinoma (22% versus 4%, P< 0.05). Post-OLT HCV infection was 99% in group A versus 4% in group B (P< 0.05). Histological hepatitis developed in 39% (66% in group A versus 14% in group B, P< 0.05) with similar follow-up. Chronic rejection occurred in 6% (3% in group A versus 8.5% in group B, P= 0.07). Retransplantation rate (overall 8%) and two-year patient survival did not differ between groups (79% versus 72%). Graft survival was higher in group A (74% versus 65% at 2 years, P= 0.04). CONCLUSIONS: HCV-cirrhosis represented the most frequent indication for OLT in Spain in 1992. While HCV recurrence was universal, de novo acquisition was rare. HCV accounted for most post-OLT hepatitis (87%), but was not associated with chronic rejection, nor with a higher retransplantation rate. Patient survival was not different in HCV patients compared to a control group after a follow-up of 2-3 years. Therefore, at present, HCV-cirrhosis is an acceptable indication for OLT.     

Transfusion-associated or nosocomial hepatitis G virus infection in patients undergoing surgery

BACKGROUND: Despite blood donor screening, there are still cases of transfusion-associated hepatitis. From 1988 to 1992, a prospective study was conducted on the incidence of non-A, non-B posttransfusion hepatitis (PTH). STUDY DESIGN: The present investigation was designed to determine if transfusion recipients with PTH who are negative for hepatitis C virus (HCV) were positive for hepatitis G virus (HGV). Patients admitted for surgery who had normal liver tests and no transfusions during the previous 6 months were enrolled. Alanine amino transferase levels were determined monthly for 6 months after surgery and for 1 year in the case of PTH (defined as alanine aminotranferase twice the upper limit of normal in two consecutive assays). HGV RNA and E2 antibodies were tested for in samples from transfusion recipients with or without PTH and from nontransfused patients. RESULTS: Of the 308 blood recipients who were enrolled in the study, 21 (6.8%) had PTH. HGV RNA was detected at the onset of hepatitis in 3 patients with PTH (14%), 2 of whom were also anti-HCV and HCV RNA positive. One patient developed E2 antibodies without detectable HGV RNA. Three (10.7%) of 28 recipients of an allogeneic transfusion without PTH developed HGV infection. HGV RNA was also found in two nontransfused patients, which suggests nosocomial transmission of HGV. CONCLUSION: Some cases of PTH are associated with HGV; most cases of postoperative HGV infection are not associated with liver abnormalities; and most PTH cases are not associated with known hepatotropic viruses.     

Serum hepatitis G virus RNA in patients with chronic viral hepatitis

OBJECTIVES: The hepatitis G virus (HGV) is a newly described flavivirus that affects a high proportion of patients with chronic viral hepatitis: our objective was to determine what role HGV might play in the course of disease. METHODS: We evaluated stored serum samples from 108 patients with chronic hepatitis B and 99 patients with chronic hepatitis C who participated in trials of alpha-interferon or ribavirin for the presence of hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA by branched DNA and for the presence of HGV RNA by polymerase chain reaction (PCR), using primers from the NS5 region of the genome. RESULTS: Initially, 20 (19%) patients with hepatitis B and 11 (11%) with hepatitis C had HGV RNA in their serum. Patients with and without HGV infection were similar with regard to clinical features, laboratory tests, and hepatic histology. HGV RNA levels fell during interferon therapy and became undetectable in those receiving the highest doses; however, HGV RNA levels returned to pretreatment values when therapy was stopped. With ribavirin therapy, HGV RNA levels did not change. Two- to 12-yr follow-up serum samples were available from 17 initially HGV RNA-positive patients, of whom only 10 (59%) were still positive. CONCLUSIONS: HGV infection is common among patients with chronic hepatitis B and C but has little effect on the short-term course of disease or response to therapy. HGV RNA levels are suppressed but not eradicated by alpha-interferon and are unaffected by ribavirin treatment. Spontaneous loss of HGV RNA occurs over time in a proportion of patients.     

C-type hepatitis in spontaneous intracerebral hemorrhage

The prevalence of hepatitis C virus (HCV) in 139 cases of spontaneous intracerebral hemorrhage (ICH) was investigated with regard to a diagnosis of hypertension. Patients under 30 and over 79 years of age were omitted from this study, and those with complicating malignancies and undergoing anti-coagulation or antiplatelet therapy were also excluded. The prevalence of HCV was significantly higher among the ICH group as a whole (19 out of 139 cases, p < 0.05) especially in the non-hypertensive group (7 out of 29 cases, p < 0.01), compared to the control group (7 out of 140 cases without ICH). The non-hypertensive HCV-positive group (7 cases) had significantly higher GOT and GPT levels, prolonged PT and a-PTT values, and lower platelet counts, compared to the hypertensive HCV-negative group (74 cases). The HCV antibody titers did not differ among the HCV-positive groups. The results suggest that chronic hepatitis due to HCV infection is a major risk factor for spontaneous intracerebral hemorrhage, especially in non-hypertensive patients.     

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 addiction, 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 hepatocytes 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.     

Exposure to blood borne viruses and the hepatitis B vaccination status among healthcare workers in inner London

The performance of a commercially available assay for detection of hepatitis C virus (HCV) antibody in saliva samples was assessed. Samples of saliva were collected from 270 individuals whose HCV antibody status was determined by serum assay (161 HCV-positive, 109 HCV-negative). The saliva samples were tested for the presence of HCV antibodies using a modified protocol. The sensitivity was 94.4% (95% CI, 89.3-97.2%) and the specificity 99.1% (95% CI, 94.3-100%). Although the optical density in tests on HIV-positive individuals was lower than that among HIV-negative individuals, the HIV status had no significant influence on the results of the HCV assay in saliva. These findings suggest that tests on saliva can be useful in epidemiological studies for estimating the prevalence of HCV in populations that are difficult to reach.     

Hepatitis G virus in the general population and in patients on hemodialysis

To determine the routes of transmission of hepatitis G virus (HGV) and the relationship between HGV and hepatitis C virus (HCV) infections, we tested for HGV RNA by polymerase chain reaction and antibody to HCV (anti-HCV) in 494 hemodialysis patients, 638 inhabitants of two HCV endemic areas, and in 400 blood donors in Japan. HGV RNA was detected in 6.9% of hemodialysis patients, in 1.4% of inhabitants, and in 0.8% of donors, and anti-HCV was detected in 39.3%, 12.4%, and 1.8%, respectively. Of HGV RNA-positive hemodialysis patients, and HGV RNA-positive inhabitants, 64.7% and 11.1%, respectively, had been given blood transfusions. The prevalences of HGV RNA and anti-HCV significantly increased with the duration of hemodialysis. Of all HGV RNA positives, 74.4% were coinfected with HCV and subjects with HGV RNA alone had normal liver function. In conclusion, HGV is transmitted by blood transfusion and within the hemodialysis unit itself. HGV does not seem to injure hepatocytes.     

High prevalence of hepatitis G virus (HGV) infection in renal transplantation

INTRODUCTION: The newly discovered (1995) hepatitis G virus (HGV) is an RNA virus from the Flaviviridae family with 85% genomic homology to GB virus C (GBV-C). We studied the prevalence of HGV infection among a cohort of 398 renal transplant recipients (RTR), all of whom had previously received blood transfusions, been grafted between August 1984 and December 1991, and been treated by cyclosporin A (CsA) as the main immunosuppressant. SUBJECTS AND METHODS: According to hepatitis C virus (HCV) antibody status, and after exclusion of 28 HBs antigen-positive recipients, this cohort had previously been divided into an HCV +ve subgroup (106 RTR; 62 M vs 44 F; 29 French vs 77 non-French) and an HCV -ve subgroup (264 RTR; 181 M vs 83 F, 196 French vs 68 non-French). We randomly selected 27 RTR in the HCV+/HBV- subgroup (14 M vs 13 F, 10 French vs 17 Italians) and 27 RTR in the HCV-/HBV- subgroup (19 M vs 8 F, 18 French vs 9 Italians) for HGV screening. The detection of HGV RNA sequences in serum (viraemia) was done by double nested RT-PCR using specific primers chosen in the 5' non-coding genomic region. The serum detection of specific antibodies (anti E2) was done by ELISA test. All sera (at time of liver biopsy or at last follow-up) were tested in duplicate. RESULTS: The prevalence of HGV viraemia was 26% (14/54) in the whole group and in both HCV +ve and -ve subgroups (7/27). The prevalence of HGV infection (viraemia + and/or anti E2 antibodies +) was 44% (24/54) in the whole group and in both HCV +ve and -ve subgroups (12/27). In addition, the prevalence was similar in males vs females and in French vs foreigners recipients (mostly Italians). In the HCV +ve subgroup, the seven HGV viraemia-positive patients who previously had liver biopsies disclosed chronic active hepatitis in four (mean Knodell score 5.75) and normal livers in three, with only one case of elevated ALT (CAH 5). In the HCV- subgroup, none of the seven HGV+ viraemic patients had elevated ALT and liver biopsy was not performed. CONCLUSION: HGV infection prevalence is high (44%) in RTR, but clearly independent of HCV status and/or the geographical origin of the recipients. This data indicates a different epidemiology as compared to our HCVs previous experience.