Int Urol Nephrol (2007) 39:1257–1263 DOI 10.1007/s11255-007-9267-x
ORIGINAL ARTICLE
Hepatitis G virus exposure in dialysis patients Ali Eslamifar Æ Rasool Hamkar Æ Amitis Ramezani Æ Farrokhlagha Ahmadi Æ Latif Gachkar Æ Somayeh Jalilvand Æ Ladan Adibi Æ Shahnaz Atabak Æ Ali Khameneh Æ Ramin Ghadimi Æ Arezoo Aghakhani
Received: 24 February 2007 / Accepted: 25 July 2007 / Published online: 5 September 2007 Ó Springer Science+Business Media B.V. 2007
Abstract Background Hepatitis G virus (HGV) is a bloodborne 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. Methods This study was performed in a major dialysis centre in Tehran, Iran. The study cohort
consisted of77 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 (antiHCV). In patients who tested positive for anti-E2, HGV RNA was detected by RT-PCR using primers
A. Eslamifar A. Ramezani A. Aghakhani (&) Clinical Research Department, Pasteur Institute of Iran, No 69, Pasteur Ave., Tehran 13164, Iran e-mail:
[email protected]
L. Gachkar Infectious Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran e-mail:
[email protected]
A. Eslamifar e-mail:
[email protected] A. Ramezani e-mail:
[email protected] R. Hamkar S. Jalilvand L. Adibi Virology Department, Tehran University of Medical Sciences, Tehran, Iran R. Hamkar e-mail:
[email protected] S. Jalilvand e-mail:
[email protected] L. Adibi e-mail:
[email protected]
S. Atabak Nephrology Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran e-mail:
[email protected] A. Khameneh Microbiology Department, Lahijan Azad University, Lahijan, Iran e-mail:
[email protected] R. Ghadimi Gastroenterology Department, Tehran University of Medical Sciences, Tehran, Iran e-mail:
[email protected]
F. Ahmadi Nephrology Department, Tehran University of Medical Sciences, Tehran, Iran e-mail:
[email protected]
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derived from the NS5A region of the viral genome. Results 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. Conclusion 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. Keywords Anti-HGV envelope protein E2 Continuous ambulatory peritoneal dialysis Haemodialysis Hepatitis G virus
Introduction Simons et al. [1] and Linnen et al. [2] independently reported a putative agent for non-A–non-E hepatitis. These viruses were named GB virus C (GBV-C) and hepatitis G virus (HGV). The viral genome of both viruses is a single-stranded RNA of approximately 9.4 kb that encodes a putative single large polyprotein of 2900 amino acids in which, similarly to hepatitis C virus (HCV), the structural proteins are positioned at the N-terminal end and the nonstructural proteins at the C-terminal end. The HGV genome encodes a single long open reading frame (ORF) coding for two putative envelope proteins (E1 and E2) and several nonstructural proteins (NS1NS5). GBV-C/HGV appears to share with HCV similar modes of transmission [3, 4]. The putative core protein that has been described in related viruses such as HCV appears to be truncated or even absent in different isolates of HGV [5]. The predominant route of HGV transmission is parenteral through exposure to contaminated blood and blood products, although other routes, such as vertical transmission or through saliva, may also exist [6–10]. It has been reported that HGV can be associated with either acute or persistent infection
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[11]. The results of some studies suggest the possibility of a link between fulminant hepatitis and HGV infection [12, 13], and there are weak associations between the transmission of HGV and the onset of acute hepatitis [11, 14] .There is no convincing evidence in favour of fulminant hepatic failure due to acute HGV infection [13]. Although HGV is able to persist in humans, chronic hepatitis due to HGV infection has not been reported to date [15]. Due to the parenteral transmission of HGV, blood transfusions are suggested to represent the main risk factor for viral infections [15]. Patients with chronic renal failure are at high risk of acquiring this virus because they require frequent blood transfusions and undergo medical procedures that accompany bleeding [16, 17]. The present data on the prevalence of HGV anti-E2 in HD patients is conflicting, with studies showing rates ranging from 7% in Japan [18] to 29% in Germany [19]. In contrast, few reports are available in patients on peritoneal dialysis treatment, but these report rates ranging from 0 by Campo et al. [20] to10.5% by Hyunjin and Fabrizi et al. [21, 22]. The only available diagnostic method for determining an ongoing GBV-C/HGV infection is to demonstrate a viremia in a patient sample by reverse transcriptase (RT)-PCR. An assay detecting antibodies to the envelope protein E2 (anti-E2) of GBV-C/ HGV has been developed, and this serological marker is considered to be an indicator of the virus clearance [23, 24]. Thus, the presence of anti-E2 seems to testify to a past GBV-C/HGV contact and is highly associated with protection from reinfection [25]. The aim of this study was to assess the frequency of HGV exposure (past infection) in HD and continuous ambulatory peritoneal dialysis (CAPD) patients serologically through the presence of anti-HGV envelope protein E2 (anti-E2). We compared HGV exposure with age, sex, time on dialysis, previous blood transfusions and co-infection with hepatitis B virus (HBV) and HCV. A secondary aim was to determine the co-existence of anti-E2 and HGV-RNA in these patients.
Patients and methods This cross-sectional study was carried out in a main dialysis centre in Tehran, Iran. Between January and March 2006, all of the dialysis patients of this centre,
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including 77 HD and 13 CAPD patients, were asked to participate in this study. A questionnaire was used to collect sociodemographic data such as age, sex, number of previous blood transfusions and length of time on dialysis. Blood samples were collected from all patients and the plasmas stored at –80°C. All samples were tested for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis C antibody (anti-HCV) and anti-E2 using the appropriateenzyme-linked immunosorbent assay (ELISA). Commercial HBsAg, anti-HBs (Hepanosticka Biomerieux, the Netherlands), anti-HCV (Bio-Rad, Italy) and anti-E2 (ClinPro Int, LLC, USA) enzyme immunoassay kits were used. All assay protocols, cut-offs and result interpretations were carried out according to the manufacturers’ instructions. A recombinant immunoblot assay (RIBA; Innogenetics, Ghent, Belgium) was employed to confirm anti-HCV reactivity.
Reverse transcriptase-PCR Anti-E2-positive samples were tested for HGV RNA by RT-PCR using primers derived from the NS5A region of the viral genome. RNA was purified from 200 ll of plasma of each sample using a viral RNA extraction kit (NucleoSpin RNA virus; MacheryNagel GmbH, Germany; Cat. no. 740 956.250) following the manufacturer’s instructions. RNA was converted to cDNA using the Superscript One-Step RT-PCR system with the random hexamer primer at 37° for 1 h. cDNA was subsequently amplified in the same tube. RT-PCR products were further amplified with nested PCR using Hot start Taq polymerase (Roche, Mannheim, Germany). The primers used in the RT-PCR/nested PCR were as follows: G58 (outer; forward), 50 -CAGGGTTGGTAGGT CGTAAATCC-30 ; G75 (outer; reverse), 50 -CCTATTGGTCAAGAGA GACAT-30 ; G134 (inner; forward), 50 -GGTCAYCYTGGTAG CCACTATAGG- 30 ; G131 (inner; reverse), 50 -AAGAGAGACATTG WAGGGCGACGT-30 . The inner primers should amplify a 208-bp region in the 50 -untranslated region (UTR) of GBV-C/HGV
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(bases 152–359) [26, 27]. An HGV-RNA positive sample was obtained from the Dr. Keivan laboratory (Tehran, Iran) and was used as a positive control. PCR products were electrophoresed on a 1.5% agarose gel containing ethidium bromide and visualized using a gel documentation system.
Statistical analysis The chi-square and t2 test were used with the SPSS ver. 11.5 package programme (SPSS, Chicago, Ill.) for statistical analysis. Data are presented as means ± standard deviation or, when indicated, as absolute numbers and percentages. A P value of \0.05 was considered to be significant.
Results A total of 77 HD patients (64% males, 36% females) with mean age of 52.1 ± 16.7 years and 13 CAPD patients (69% males, 31% females) with a mean age 52.1 ± 19.3 years participated in the study. HD patients had been on dialysis for a mean of 55.6 ± 57.6 months (range 1–218 months), and CAPD patients for a mean of 9.4 ± 7.6 months (range 1–24 months). Eighty-one percent of HD patients and 15% of CAPD patients had previously received a blood transfusion (HD patients: mean 4.9 ± 3.5 transfusions; CAPD patients: 0.31 ± 0.85 transfusions). Three of the 77 HD patients tested positive for anti-E2 (3.89%). The mean age of patients testing positive for anti-E2 was 53.3 ± 26.5 years, and that of patients with negative anti-E2 was 49.1 ± 16.4 years. In none of the anti-E2 positive patients was HGV RNA detected. Anti-HCV antibodies, HBsAg and anti-HBs Ab were found in 6.49, 6.49 and 57.14% of the HD patients, respectively. In anti-E2-positive patients, co-infection with HCV or HBV was not significant. Blood transfusion(s) had been received previously by 66.66% of the anti-E2positive patients and by 86.48% of the anti-E2negative patients. The mean duration of haemodialysis in anti-E2 positive and anti-E2 negative patients was 68 ± 64 and 48.2 ± 55.5 months, respectively. Anti-E2 was not detected in any of the CAPD patients, and none of the CAPD patients tested
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Table 1 Patient’s characteristics (NS not significant) Haemodialysis
Continuous ambulatory peritoneal dialysis
P value
Number of patients
77
13
–
Age (years)
52.1 ± 16.7
52.1 ± 19.3
NS
Sex (M:F)
49:28
9:4
NS
HbsAg (+)
5 (6.49%)
0
NS
Anti-HBs (+)
44 (57.14%)
0
NS
Ant- HCV (+) Anti-E2 (+)
5 (6.49%) 3 (3.89%)
0 0
NS NS
Values are the mean ± standard deviation NS, Not significant
positive for anti-HCV antibodies, HBsAg and antiHBsAb. The mean age, male:female ratio and prevalence of HCV and HBsAg were not significantly different between the HD and CAPD patients. The prevalence of HBsAb was significantly higher in HD patients than in CAPD patients (57.14% vs. 0, P \ 0.001) (Table 1).
Discussion Patients undergoing dialysis potentially have an increased risk of infection with parenterally transmitted viral agents due to an impaired host immune response and multiple transfusion requirements [28]. This is particularly the case for HD patients, for whom transmission by contamination during dialysis cannot be ruled out. Viral hepatitis has been recognized as a relevant problem for these patients because 1.9% of all deaths among this population are regarded to be the consequence of viral hepatitis [29]. GBV-C/ HGV is transmitted mainly by parenteral mode. Thus, patients with chronic renal failure are at high risk of acquiring this virus because they need frequent blood transfusions and undergo medical procedures that involve direct contact with blood [30]. The existing data on GBV-C/HGV RNA prevalence in chronic dialysis patients, however, is conflicting [31]. Time on haemodialysis, transfusion requirements and renal transplantation are risk factors for hepatitis G virus (HGV) infection in patients on maintenance HD, with transversal studies reporting a prevalence ranging
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from 3 to 57% [14, 16, 17, 32–35]. GBV-C/HGV RNA prevalence rates in HD patients range from 11.5 to 27% in the USA [36, 37], from 6 to 57.5% in Europe [14, 17] and, in Asia, from less than 2.2% in India [38] to 55% in Indonesia [39]. In one preliminary study from Iran reported that the sera of patients on maintenance HD were negative for GBV-C [40]. In contrast, few reports are available on HGV prevalence in patients on CAPD treatment who are also at increased risk of GBV-C/HGV infection [21]. HGV-RNA prevalence rates in CAPD patients have been reported to vary from 12.7 to 23.3%, depending on the study [21, 22, 41]. Anti-HGV envelope protein E2 occurs mostly after the loss of HGV-RNA in the serum and indicates a previous HGV infection with spontaneous clearance virus [42]. In our study, 3.89% of the HD patients and none of the CAPD patients tested positive for anti-E2, showing that HGV exposure was low in this population of dialysis patients. This low prevalence of HGV exposure may be explained by epidemiological factors, including the size and clinical features of the patients, as well as geographic factors; for example, anti-E2 positivity has been shown to be significantly lower in Asian countries than Europe [43]. It also may be due to infection control measures practiced in the dialysis unit. In European countries, anti-E2 seropositivity has been reported to range from 10.9% (Germany) to 15.3% (Austria), while even higher anti-E2 prevalence rates have been recorded in South Africa (20.3%) and Brazil (19.5%). In Asian countries, such as Bhutan (3.9%), Malaysia (6.3%) and the Philippines (2.7%), anti-E2 positivity was significantly lower [43]. The prevalence of anti-E2 antibodies in HD patients has been established in several studies, with reported antibody rates of 12.9– 29% in Germany [19, 44], 22% in Austria [45], 14.2% in Belgium [46], 7% in Japan [18] and 15.6% in Taiwan [41]. Little data are available on patients on peritoneal dialysis treatment; however, rates ranging from 0 [20] to10.5% [21, 22] have been reported. The simultaneous detection of viral RNA and antiE2 antibody seems to be rare and occurs only for a limited time interval [47]. In most cases, anti-E2 serological positivity is associated with the loss of detectable HGV-RNA [48]. In rare cases, however, HGV-RNA and anti-E2 may be detected simultaneously. The coexistence of the HGV viremia and the anti-E2 appears just before clearance, probably in the
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form of an immunocomplex [49]. In our study, none of the anti-E2-positive patients tested positive for HGV RNA, indicating that the appearance of the antibody is accompanied by a clearance of serum HGV-RNA, which confirms results found in other studies [24, 33]. In a French study, none of the blood specimens that tested positive for anti-E2 were also positive for GBV-C/HGV RNA [33]. In a German study, 3% of patients were positive for both antibodies and HGV-RNA [50]. This overlapping was observed in 0.6% of the samples testedin a Taiwanese study [41]. Numerous authors have reported an association between HCV, HBV and GBV-C/HGV [35, 48, 51]. In our study, HGV-exposed patients were not co-infected with HCV or HBV, indicating that HGV is capable of independent transmission. This may be due to the low prevalence of HCV and HBV infection and the low number of anti-E2-positive patients in our study. Tanaka et al. demonstrated HGV and HCV coinfection in 11% of patients with chronic HCV [52]. Martinot et al. found HGV infection in 21% of patients with chronic HCV and in 32% of injecting drug users [53]. Fabrizi et al. reported that the frequency of anti-HCV antibody was significantly higher in HGV-positive than in HGV-negative patients on chronic HD treatment and that the rate of co-infection with HGV and HCV in HD patients was 82% [54]. In an Italian study, none of the HGVpositive HD patients were found to be co-infected with HCV [55], while in a Brazilian study, 22% of the GBV-C/HGV-positive HD patients were coinfected with HCV [56]. However, whether these results can be explained simply by common modes of transmission (transfusion, sexual contact) or whether HCV actually influences, for example, the persistence or replication efficiency of GBV-C/HGV remains to be established. Suboptimal infection control strategies may account for the high prevalence of HCV and GBV-C/HGV in some HD units [39]. Patients on CAPD usually show a lower frequency of anti-HCV antibody than undergoing HD [22]. Fabrizi et al. reported that there is no relationship between anti-E2 positivity and HCV markers in CAPD patients [22]. Some studies have reported co-infection with HGV and HBV in dialysis patients, with rates varying from 2.2 to 13% in HD patients [35, 57, 58]. Other studies, however, have not found any association between these viral infections [22].
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In several studies there were no significant differences between HGV-positive and -negative patients on chronic dialysis treatment in terms of age and sex [35, 44]. The transfusion requirement appears to be an important risk factor for GBV-C/HGV transmission in dialysis patients [16, 17, 35, 48], as are time on dialysis [17, 35, 46] and renal transplantation [48]. Our study showed that there was no association between HGV exposure and age, sex, history of blood transfusion and length of time on dialysis. Similar results were obtained by Filho et al., who reported that there was no association between GBV-C/HGV infection and age, sex, history of blood transfusion and length of time on dialysis in HD patients [56], and Huang et al. [41]. In conclusion, HGV exposure rate was low in dialysis patients in our investigation, although the real prevalence of HGV infection could be higher than that assessed solely by anti-HGV antibody testing. In all of the patients tested, the appearance of anti-E2 was accompanied with the clearance of serum HGV-RNA. In HGV-exposed patients, coinfection with HCV or HBV was not seen, indicating that HGV is capable of independent transmission. There was no association between HGV exposure and age, sex, history of blood transfusion, length of time on dialysis and/or the presence of HBV or HCV. The clinical significance of HGV and modes of it’s acquisition in dialysis patients still remains unclear and needs further investigation. Acknowledgements The authors are grateful to the Pasteur Institute of Iran for financial support of this study. Special thanks are extended to Ms. Jaleh Taeb for her contribution in writing this publication.
References 1. Simons JN, Leary TP, Dawson GJ et al (1995) Isolation of novel virus-like sequences associated with human hepatitis. Nat Med 1:564–569 2. Linnen J, Wages J, Zhang-Keck ZY et al (1996) Molecular cloning and disease association of hepatitis G virus: a transfusion-transmissible agent. Science 271:505–508 3. Roth WK, Waschk D, Marx S et al (1997) Prevalence of hepatitis G virus and its strain variant, the GB agent, in blood donations and their transmission to recipients. Transfusion 37:651–656 4. Katayama K, Kageyama T, Fukushi S et al (1998) Fulllength GBV-C/HGV genomes from nine Japanese isolate: characterization by comparative analyses. Arch Virol 143:1063–1075
123
1262 5. Li G, Ma HH, Lau GK, Leung YK, Yao CL, Chong YT, Tang WH Yao JL (2002) Prevalence of hepatitis G virus infection and homology of different viral strains in Southern China. World J Gastroenterol 8:1081–1087 6. Lefre`re JJ, Roudot TF, Morand JL, Brossard Y et al (1999) Prevalence of GB virus type C/hepatitis G virus RNA and of anti-E2 in individuals at high or low risk for blood-borne or sexually-transmitted viruses: evidence of sexual and parenteral transmission. Transfusion 39:83–94 7. Lefrere JJ, Sender A, Mercier B et al (2000) High rate of GB virus type C/HGV transmission from mother to infant: possible implications for the prevalence of infection in blood donors. Transfusion 40:602–607 8. Chen M, Sonnerborg A, Johansson B, Sallberg M (1997) Detection of hepatitis G virus (GB virus C) RNA in human saliva. J Clin Microbiol 35:973–975 9. Seemayer CA, Viazov S, Philipp T, Roggendorf M (1998) Detection of GBV-C/HGV RNA in saliva and serum, but not in urine of infected patients. Infection 26:39–41 10. Yashina TL, Favorov MO, Khudyakov YE et al (1997) Detection of hepatitis G virus (HGV) RNA: clinical characteristics of acute HGV infection. J Infect Dis 175:1302– 1306 11. Ling BH, Zhuang H, Cui YH et al (1998) A cross-sectional study on HGV infection in a rural population. World J Gastroenterol 4:489–492 12. Moaven LD, Locarnini SA, Bowden DS et al (1997) Hepatitis G virus and fulminant hepatic failure: infection. J Hepatol 27:613–619 13. Sheng L, Soumillion A, Beckers N et al (1998) Hepatitis G virus infection in acute fulminant hepatitis: prevalence of HGV infection and sequence analysis of a specific viral strain. J Viral Hepatitis 5:301–306 14. Corun C, Jadoul M, Loute G, Goubau P (1997) Hepatitis G virus infection in haemodialysis patients: epidemiology and clinical relevance. Nephrol Dial Transplant 12:1326– 1329 15. Alter HJ, Nakatsuji Y, Melpolder J et al (1997) The incidence of transfusion-associated hepatitis G virus infection and its relation to liver disease. N Engl J Med 336:747–757 16. Masuko K, Mitsui T, Iwano K et al (1996) Infection with hepatitis GB virus C in patients on maintenance hemodialysis. N Engl J Med 334:1485–1490 17. De Lamballerie X, Charrel RN (1996) Hepatitis GB virus C in patients on hemodialysis. N Engl J Med 334:1549 18. Shibuya A, Takeuchi A, Kamata K et al (1998) Prevalence of hepatitis G virus RNA and anti-E2 in a Japanese haemodialysis population. Nephrol Dial Transplant 13:2033– 2036 19. Schulte-Frohlinde E, Schmolke S, Reindl W et al (1998) Significance of antibodies to recombinant E2 protein of hepatitis G virus in haemodialysis patients. J Viral Hepat 5:341–344 20. Campo N, Sinelli N, Brizzolara R et al (1999) Hepatitis G virus infection in haemodialysis and in peritoneal dialysis patients. Nephron 82:17–21 21. Hyunjin N, Kang SW, Choi SH et al (1998) Hepatitis G virus infection in hemodialysis and continuous ambulatory peritoneal dialysis patients. Yonesi Med J 39:116–121
123
Int Urol Nephrol (2007) 39:1257–1263 22. Fabrizi F, De Vecchi AF, Lunghi G et al (2002) Epidemiology of GB virus C/Hepatitis G virus infection in patients on peritoneal dialysis. Perit Dial Int 22:405–410 23. Dille BJ, Surowy TK, Gutierrez RA et al (1997) An ELISA for detection of antibodies to the E2 protein of GB virus C. J Infect Dis 175:458–461 24. Tacke M, Kiyosawa K, Stark K et al (1997) Detection of antibodies to a putative hepatitis G virus envelope protein. Lancet 349:318–320 25. Thomas DL, Vlahov D, Alter HJ et al (1998) Association of antibody to GB virus C (hepatitis G virus) with viral clearance and protection from reinfection. J Infect Dis177:539–542 26. Sugai Y, Nakayama H, Fukuda M et al (1997) Infection with GB virus C in patients with chronic liver disease. J Med Virol 51:175–181 27. Andonov A, Sauder C, Jacobsen H, Chaudhary R (1998) Comparison of six sets of PCR primers from two different genomic regions for amplification of GB virus C/hepatitis G virus RNA J Clin Microbiol 36:286–289 28. Goldblum SE, Reed WP (1980) Host defenses and immunologic alternations associated with chronic hemodialysis. Ann Intern Med 93:597–613 29. Jacobs C, Brunner FP, Chantler C et al (1977) Combined report on regular dialysis and transplantation in Europe, VII, 1976. Proc Eur Dial Transplant Assoc 14:3–69 30. Sheng L, Widyastuti A, Kosala H et al (1998) High prevalence of hepatitis G virus infection compared with hepatitis C virus infection in patients undergoing chronic hemodialysis. Am J Kidney Dis 31:366–368 31. Fabrizi F, Martin P (1999) GBV-C/HGV infection in endstage renal. J Nephrol 12:131–139 32. Cabrerizo M, Bartolome J, de Sequera P et al (1999) GBVC/HGV-RNA in serum and peripheral blood mononuclear cells in hemodialysis patients. Kidney Int 56:1120–1128 33. Desassis JF, Laperche S, Girault A et al (1999) Prevalence of present and past hepatitis G virus infection in a French hemodialysis centre. Nephrol Dial Transplant 14:2692– 2697 34. Konomi N, Miyoshi C, Zerain CF et al (1999) Epidemiology of hepatitis B, C, E and G virus infection and molecular analysis of hepatitis G isolates in Bolivia. J Clin Microbiol 37:3291–3295 35. Forns X, Fernandez-Llama P, Costa J et al (1997) Hepatitis G virus infection in a haemodialysis unit: prevalence and clinical implications. Nephrol Dial Transplant 12:956–960 36. Bastani B, Frenche D, Gellens M, Di Bisceglie A (1998) Infection with hepatitis G (HGV) and hepatitis C (HCV) viruses in patients on chronic hemodialysis. Am J Nephrol 9:199A 37. Medina M, Ashby M, Schlu¨ter V et al (1998) Prevalence of hepatitis C and G virus infection in chronic hemodialysis patients. Am J Kid Dis 31:224–226 38. Desai XX, Pal RB, Banker DD (2004) GB virus C/hepatitis G virus infection in Indian blood donors and high-risk groups. Transfus Apher Sci 30:111–117 39. Tsuda F, Hadiwandowo S, Sawada N et al (1996) Infection with GB virus C (GBV-C) in patients with chronic liver disease or on maintenance hemodialysis in Indonesia. J Med Virol 49:248–252
Int Urol Nephrol (2007) 39:1257–1263 40. Zali MR, Mayumi M, Raoufi M, Nowroozi A (1999) GBVC infection among patients with hepatitis C virus in the Islamic Republic of Iran: a preliminary report. East Mediterr Health J 5:1023–1029 41. Huang JJ, Lee WC, Ruaan MK et al (2001) Incidence, transmission, and clinical significance of hepatitis G virus infection in hemodialysis patients. Eur J Clin Microbiol Infect Dis 20:374–379 42. Pilot-Matias TJ, Carrick RJ, Coleman PF et al (1996) Expression of the GB virus E2 glycoprotein using the Semliki Forest virus vector system and its utility as a serologic marker. Virology 255:282–292 43. Ross RS, Viazov S., Schmitt U et al (1998) Distinct prevalence of antibodies to the E2 protein of GB virus C/ hepatitis G virus in different parts of the world (abstr). J Med Virol 54:103–106 44. Szabo A, Viazov S, Heemann U et al (1997) GBVC/HGV infection in renal dialysis and transplant patients. Nephrol Dial Transplant 12:2380–2384 45. Tribl B, Oesterreicher C, Pohanka E et al (1998) GBV-C/ HGV in hemodialysis patients: Anti-E2 antibodies and GBV-C/RNA in serum and peripheral blood mononuclear cells. Kidney Int 53:212–216 46. Kallinowski B, Ahmadi R, Seipp S et al (1998) Clinical impact of GB-C virus in haemodialysis patients. Nephrol Dial Transplant 13:93–98 47. Lefre`re JJ, Loiseau P, Maury J et al (1997) Natural history of GBV-C/hepatitis G virus infection through the followup of GBV-C/hepatitis G virus-infected blood donors and recipients studied by RNA polymerase chain reaction and Anti-E2 serology Blood 90:3776–3780 48. Stra´nsky´ J (1996) Discovery of hepatitis G virus. J Czech Physicians 4:99–101 49. Mushahwar IK, Zuckerman JN (1998) Clinical implications of GB virus-C. J Med Virol 56:1–3
1263 50. Hinrichsen H, Leimenstoll G, Stegen G et al (2002) Prevalence of and risk factors for hepatitis G (HGV) infection in haemodialysis patients: a multicentre study. Nephrol Dial Transplant 17:271–275 51. Wang Y, Chen HS, Fan MH et al (1997) Infection with GB virus C and hepatitis C virus in hemodialysis patients and blood donors in Bejing. J Med Virol 52:26–30 52. Tanaka E, Alter HJ, Nakatsuji Y et al (1996) Effect of hepatitis G virus infection on chronic hepatitis C. Ann Int Med 125:740–743 53. Martinot M, Marcellin P, Boyer N et al (1997) Influence of hepatitis G virus infection on the severity of liver disease and response to interferon alpha in patients with chronic hepatitis C. Ann Int Med 126:874–881 54. Fabrizi F, Lunghi G, Bacchini G et al (1997) Hepatitis G virus infection in chronic dialysis patients and kidney transplant recipients. Nephrol Dial Transplant 12:1645– 1651 55. Tringali G (1998) Prevalence of HGV infection in hemodialysis patients from eastern Sicily, Giorn. Ital Nefrol 15:141–147 56. Filho RR, Carneiro M.AS, Teles SA et al (2004) GB virus C/hepatitis G virus infection in dialysis patients and kidney transplant recipients in central Brazil, Mem Inst Oswaldo Cruz 99:639–643 57. Klusonova H, Pliskova L, Palicka V, Fixa P (2001) Prevalence of viral hepatitis G infection in hemodialysis patients and coinfection with viral hepatitis B and C. Vnitr Lek 47:678–681 58. Lopez-Alcorocho JM, Barril G, Ortiz-Movilla N et al (2001) Prevalence of hepatitis B, hepatitis C, GB virus C/ hepatitis G and TT viruses in predialysis and hemodialysis patients. J Med Virol 63:103–107
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