Apoptosis and hepatitis C virus infection in renal transplant recipients

Hepatocellular injury in renal transplant recipients with hepatitis C virus (HCV) infection remains unclear. The suppressed immune response, in combination with increased viremia levels, provides a unique setting for the study of a potential HCV-induced apoptotic process.Liver biopsy specimens from 59 HCV-infected renal transplant recipients were examined histologically. DNA fragmentation was detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling assay, and the CD8 T-cell count was assessed immunohistochemically.A low apoptotic index (0-2.5) was observed in 31 cases, a moderate index (2.6-5) in 16, and a high index (>5) in 12. Apoptotic cell death correlated significantly with viremia because it was demonstrated by higher HCV-RNA levels in cases with a high number of apoptotic cells (odds ratio, 2.96; 95% confidence interval, 1.0-8.5; P = .04). No correlation was found between the apoptotic index and hepatitis necroinflammatory activity, CD8 cell count, fibrosis stage, immunosuppressive therapy, or genotype.In HCV-infected renal transplant recipients, apoptotic cell death seems to be associated with high viral load, thus providing indications of viral interference in the pathogenetic process.     

Prevalence of hepatitis B, hepatitis C, GB virus C/hepatitis G and TT viruses in predialysis and hemodialysis patients

Patients with chronic renal failure on hemodialysis have a high risk of infections with viruses such as hepatitis B (HBV), hepatitis C (HCV), GB virus C/hepatitis G (GBV-C/HGV) and TT (TTV) viruses. The prevalence of HBV, HCV, GBV-C/HGV and TTV in patients with chronic renal failure who are on conservative management before entering into a hemodialysis program (predialysis) in comparison with hemodialyzed patients was studied to elucidate whether the high prevalence of these viruses is influenced by that observed in the predialysis stage. The presence of hepatitis B virus surface antigen (HBsAg), HCV RNA, GBV-C/HGV RNA and TTV DNA was analyzed in sera from 80 patients with chronic renal failure (35 on predialysis and 45 on hemodialysis). HBsAg, HCV RNA, GBV-C/HGV RNA and TTV DNA were detected in one (2.8%), six (17.1%), eight (22.5%) and 16 (45.7%) of the 35 patients on predialysis. Two (5.7%) of these patients were coinfected with HCV and GBV-C/HGV, whereas six (17.1%) had GBV-C/HGV and TTV coinfection. In the 45 hemodialyzed patients, HBsAg, HCV RNA, GBV-C/HGV RNA and TTV DNA were detected in one (2.2%), two (4.4%), seven (15.5%) and 26 (57.7%). One (2.2%) patient had HBV and TTV coinfection, two (4.4%) HCV and TTV coinfection whereas four (8.8%) were coinfected with GBV-C/HGV and TTV. No differences regarding age, gender, previous surgery and number of transfusions were found between infected and uninfected patients within and between both groups. In conclusion, the prevalence of the viruses studied in predialysis may influence their prevalence in dialysis units.     

Effects of GB virus-C/hepatitis G virus on hepatitis B and C viremia in multiple hepatitis virus infections

Summary.  We found that patients with dual HBV and GBV-C/HGV infection had comparable serum HBV DNA positivity and mean virus concentration compared with age-matched HBV carriers, and those with triple infection had a significantly lower HBV DNA positivity. Serum HCV RNA positivity and mean virus titer were similar between HCV carriers with or without GBV-C/HGV co-infection, and those with GBV-C/HGV co-infection seemed to have a lower serum ALT level. These data suggest that GBV-C/HGV infection exerts no significant suppression on levels of chronic hepatitis B or hepatitis C viremia. Accepted December 4, 1997 Received September 8, 1997     

Sexual transmission of GB virus C/hepatitis G virus

Although it is established that infection with GB virus C (GBV-C) or hepatitis G virus (HGV) can be transmitted parenterally, the prevalence of GBV-C/HGV viremia in the general population (2–5%) is relatively high compared with other parenterally borne viruses such as hepatitis C virus. To investigate the possibility of sexual transmission of GBV-C/HGV, we determined the frequency of viremia by the polymerase chain reaction and serological reactivity to the E2 protein by ELISA in samples collected from individuals at risk for sexually transmitted diseases attending a city genitourinary medicine clinic. GBV-C/HGV viremia was detected in 27 of 87 male homosexuals (31%) and 9 of 50 prostitutes (18%), frequencies significantly greater than those in matched controls (2/63) and local blood donors (2.3%). Among nonviremic individuals, a high frequency of serological reactivity to the E2 protein of GBV-C/HGV was also observed in the risk groups (male homosexuals: 14/60; prostitutes: 11/41), although these figures are likely to be underestimates of the frequency of past infection as detectable anti-E2 reactivity may attenuate rapidly over time following resolution of infection. Infection with GBV-C/HGV was more frequent among those coinfected with human immunodeficiency virus type 1. Among male homosexuals from whom retrospective samples were available, evidence for de novo infection was found in 9 of 22 individuals over a mean sampling time of 2.9 years, predicting an annualized incidence of GBV-C/HGV infection of approximately 11% in this group. The high prevalence and incidence of GBV-C/HGV infection in these individuals and prostitutes provides strong evidence for its spread by sexual contact. Further studies are required to investigate the mechanism of its transmission and the clinical significance of acute and persistent infection in these risk groups. J. Med. Virol. 55:203–208, 1998. © 1998 Wiley-Liss, Inc.     

Lack of anti-GOR antibody among subjects with GB virus C/hepatitis G virus RNA

Homologies were sought between the putative amino acid sequences of GB virus C/hepatitis G virus (GBV-C/HGV) and the GOR epitope or the liver/kidney microsome-1 (LKM-1) epitope, which share partial sequence identity with the hepatitis C virus (HCV) polyprotein. Anti-GOR antibody (anti-GOR) was assayed among 100 subjects with GBV-C/HGV RNA. Twenty-one and 25 subjects were coinfected with hepatitis B virus (HBV) or HCV, respectively. Homologies were found between the NS5 or E2 polyproteins of GBV-C/HGV and the GOR epitope or the LKM-1 epitope, respectively. These segments of GBV-C/HGV polyproteins sharing identity with the GOR or the LKM-1 epitope were well conserved among three genotypes of GBV-C/HGV. However, only 1 of 55 subjects (1.8%) with GBV-C/HGV RNA, but not with HBV or HCV, was positive for anti-GOR. The positivity for anti-GOR among the group with GBV-C/HGV RNA alone was significantly lower than that among the groups with HCV RNA (P < 0.01 and P < 0.05, respectively). Only 2 of 55 subjects (3.6%) with GBV-C/HGV RNA alone exhibited elevation of alanine aminotransferase. The incidence of liver dysfunction among the group with GBV-C/HGV RNA alone was significantly lower than the incidence among the groups with GBV-C/HGV RNA and hepatitis B surface antigen (HBsAg) or HCV RNA (P < 0.01 and P < 0.01, respectively). These data indicate that 1) there is no association between GBV-C/HGV infection and the presence of anti-GOR, and 2) GBV-C/HGV infection is not related to chronic liver dysfunction. J. Med. Virol. 55:129–133, 1998. © 1998 Wiley-Liss, Inc.     

Prevalence of infections in renal transplant recipients of north India

Renal transplant is usually performed at the end stage of renal disease. Most of the transplant recipients become susceptible to infections due to chronic uremia, protein depletion, anemia and administration of immunosuppressive drugs. It is a retrospective study of 510 post renal transplant recipients. 378 (74%) renal transplant recipients suffered from the infections. Most common site of infection was urinary tract infection (53%). Out of 26% of wound infections, the deep wound infection (23%) was six times higher than superficial wound infection (3.5%). Chest infection and bacteraemia were noticed to be 18% and 8%, respectively. The common isolate was Escherichia coli (160) followed by Staphylococcus aureus (140), Enterococcus (86) and Pseudomonas (69).     

High prevalence of GB virus C/hepatitis G virus genotype 3 among autochthonous Venezuelan populations

GB virus C or hepatitis G virus (GBV-C/HGV) is highly prevalent among population groups at risk of parenterally transmitted viral agents, but it has also a worldwide distribution in other non-risk population groups. GBV-C/HGV RNA and antibodies against its envelope protein (anti-E2 Abs) were found in 3/86 (3%) and 7/89 (8%) of biomedical science personnel (BSP), in 31/453 (7%) and 37/200 (19%) of blood donors (BD), and in 6/64 (9%) and 26/59 (44%) of hemodialysis patients (HD) from Caracas, Venezuela. A significant gradient of GBV-C/HGV exposure (anti-E2 Abs and/or GBV-C/HGV RNA) was found between BSP (lowest prevalence), BD, and HD (P < 0.001). GBV-C/HGV RNA and anti-E2 Abs were also found in 2/69 (2.9%) and 2/44 (4.5%) of individuals from a rural community, in 9/162 (5.5%) and 2/40 (5%) of West Amerindians, and in 14/56 (25%) and 4/53 (7.5%) of South Amerindians. Socioeconomic and cultural factors may have contributed to the relatively high risk of exposure to GBV-C/HGV in BD and Amerindians. Whereas GBV-C/HGV genotypes 1 (n = 1), 2 (n = 6), and 3 (n = 22) were present in Venezuela, only the Asiatic genotype 3 was found infecting Amerindians and rural populations (n = 16). Genotype assignment based on the 5' noncoding region of the GBV- C/HGV genome was corroborated in some isolates by genetic analysis of the E2 region. This report confirms the circulation of the Asiatic genotype of GBV-C/HGV among Amerindians, suggesting an old origin of GBV-C/HGV. This might be associated with the apparently low pathogenesis of this virus.     

Viral infections in renal transplant recipients.

Cytomegalovirus (CMV) infections are common in renal transplant recipients. We studied 23 recipients prospectively to determine whether infections by other herpes-group and non-herpes-group viruses were also present. Sera, obtained at the time of surgery and periodically thereafter, were tested for antibody to CMV, herpes simplex virus (HSV), Epstein-Barr virus (EBV), parainfluenza viruses types 1, 2, and 3, and the viruses of measles and rubella. We found no evidence of an unusual incidence of primary or secondary infection by the non-herpesviruses tested. Rises to CMV, HSV, and EBV antibody titers occurred in 43, 38, and 32% of patients, respectively. All serological rises to herpes-group viruses occurred in patients seropositive at the time of transplantation, with the exception of three patients who experienced primary CMV infections. We conclude that reactivation of all herpes-group viruses tested may occur in transplant recipients. Morbidity was associated only with primarly CMV infection.     

High prevalence of GB virus C/hepatitis G virus infection in different risk groups of HIV-infected patients

Objectives: To investigate the prevalence of GB virus C (GBV-C)/hepatitis G virus (HGV) RNA and anti-E2 antibodies in different risk groups of HIV-infected patients compared to that in healthy blood donors, and to study the effects of possible interactions between HIV and GBV-C/HGV on the carrier state and hepatic changes.
Methods: Sera from 100 consecutive unselected HIV-infected outpatients and from 100 healthy blood donors were screened for GBV-C/HGV viremia and anti-E2 antibodies. Anti-E2 antibodies were detected using an immunoassay developed by Boehringer Mannheim according to the manufacturer's instructions. GBV-C/HGV RNA was extracted from sera and reverse transcribed. The resulting cDNA was amplified with a PCR developed in the laboratory with primers derived from the 5' noncoding region of the viral genome and detected with a specific capture probe. This procedure was validated by a French multicenter quality control group.
Results: Thirty-one of the 100 HIV-infected patients and 8% of the healthy blood donors displayed anti-E2 antibodies. Four HIV-infected patients and one healthy blood donor were found to be GBV-C/HGV viremic. When analyzed by risk factor for the acquisition of HIV, no differences in the prevalence of anti-E2 antibodies were found between intravenous drug users and homosexual and heterosexual patients.
Conclusions: We found a high prevalence of GBV-C/HGV infection in the HIV-infected population, irrespective of the risk group factor for HIV infection, suggesting that the sexual route is as effective as the parenteral route for the acquisition of GBV-C/HGV. No biological alteration could be attributed to GBV-C/HGV, even in the viremic patients. HIV-infected patients were able to clear GBV-C/HGV viremia and to mount a humoral immune response.     

Persisting TT virus (TTV) genogroup 1 variants in renal transplant recipients

Summary.  TT virus (TTV) genogroup 1 infection has an increased prevalence in solid organ transplant recipients. In this study, the presence of TTV in renal transplant recipients was examined by two PCR methods, one capable of detecting most TTV genotypes (UTR-PCR), the other specific to genogroup 1 (N22-PCR). The N22-PCR detected TTV in 57% (53/92) of the renal transplant patients and in 20% (13/66) of the healthy individuals, while the prevalence of TTV with the UTR-PCR was above 90% in both the control and the patient groups. The N22-PCR was used in longitudinal studies of 31 renal transplant recipients, these PCR products were sequenced and aligned. TTV status was not associated with the patients’ age at transplantation, male to female ratio and the time lag between kidney transplantation and the TTV test. During the follow-up consistent TTV status was found in 26 patients, while two initially TTV positive patients converted to negative and three initially negative patients converted to positive. The TTV variants varied among the tested patients, but were the same in the consecutive samples of each patient, indicating that TTV infection was persistent in renal transplant recipients and novel infection occured rarely in the post-transplant period. Received October 2, 2002; accepted December 27, 2002 Published online March 13, 2003     

Frequencies of GB virus C/hepatitis G virus genomes and of specific antibodies in German risk and non-risk populations

The prevalence of the new flavivirus GB virus C/hepatitis virus G (GBV-C/HGV) in different German populations was investigated by detection of viral genomes and anti-E2 antibodies. While blood donors had an overall prevalence of 10.4% there were increased rates for hemophiliacs (54.7%), hemodialysis patients (30.2%), male homosexuals (30.2%) and intravenous drug users (74.4%). Most GBV-C/HGV positive samples were either viral genome positive or antibody positive, exclusively. Samples with the rare constellation “positive for both GBV-C/HGV genome and specific antibody” originated in almost all cases from patients who were additionally infected with HIV or HCV. Probable transmission of GBV-C/HGV by PCR-positive blood transfusions was observed in 5 of 6 cases approximately six months after transfusion. J. Med. Virol. 53:218–224, 1997. © 1997 Wiley-Liss, Inc.     

Genetic heterogeneity and molecular epidemiology of GB virus C/hepatitis G virus in China

OBJECTIVE: The inter- and intrapatient genetic variation of GB virus C (GBV-C)/hepatitis G virus (HGV) was investigated to characterize the molecular epidemiologic profile of GBV-C/ HGV infection in China, an area endemic for viral hepatitis. The intrapatient variation of hepatitis C virus (HCV) from the same patients was compared to that of GBV-C/HGV. STUDY DESIGN/METHODS: GB virus C/HGV RNA was amplified by polymerase chain reaction in 88 patients with hepatitis C, hepatitis B or presumed non-A-E hepatitis from three cities in China. Five clones of the GBV-C/HGV NS3 region were sequenced from each GBV-C/HGV RNA-positive patient. The corresponding region of HCV was also sequenced from patients co-infected with HCV. Representative sequences of the GBV-C/HGV NS3 region from each patient and those of isolates from other continents were subjected to phylogenetic analyses. RESULTS: GB virus C/HGV was detected in 22 (25.25%) of 88 patients: 9 (21.4%) of 42 patients with presumed non-A-E hepatitis, 10 (27.7%) of 36 patients with hepatitis C, 3 (30.0%) in 10 patients with hepatitis B and C, and in none of 60 volunteer blood donors. The extent of nucleotide variation was less between Chinese isolates (2.4-17%; median, 10.4%) than between Chinese isolates and seven isolates from outside China (10.5-19.5%; median, 15.3%). Intrapatient sequence variation ranged from 0 to 1.75%, with a mean of 0.57 +/- 0.51%. Phylogenetic analysis grouped most Chinese isolates into four geographically specific clusters with a divergence of 10% to 16% from each other. The ratio of nonsynonymous to synonymous substitutions of GBV-C/HGV (Ka/Ks 0.019) was much lower than for HCV (0.071) in the same patients. CONCLUSION: Chinese isolates of GBV-C/HGV are genetically distinct. There are local strains as well as shared strains between different locales. The extent of amino acid sequence conservation suggests strong selection against nonsynonymous substitutions in the GBV-C/HGV genome.