Antibodies against non-structural c100/3 and structural core antigen of hepatitis C virus (HCV) in hemodialysis patients

Yoshida, C.F.T.; Takahashi, Y.; Vanderborght, B.O.M.; Rouzere, C.D.; França, M.S.; Takahashi, C.; Takamizawa, A.; Yoshida, I.; Schatzmayr, H.G.

doi:10.1590/S0036-46651993000400002

Abstracts

Two groups of patients undergoing hemodialysis (HD) maintenance were evaluated for their antibody response to non-structural c100/3 protein and structural core protein of hepatitis C virus (HCV). Forty-six patients (Group 1) never presented liver abnormalities during HD treatment, while 52 patients (Group 2) had either current or prior liver enzyme elevations. Prevalence rates of 32.6% and 41.3% were found for anti-c100/3 and anti-HCV core antibodies, respectively, in patients with silent infections (Group 1). The rate of anti-c100/3 in patients of Group 2 was 71.15% and reached 86.5% for anti-HCV core antibodies. The recognition of anti-c100/3 and anti-core antibodies was significantly higher in Group 2 than in Group 1. A line immunoassay composed of structural and non-structural peptides was used as a confirmation assay. HBV infection, measured by the presence of anti-HBc antibodies, was observed in 39.8% of the patients. Six were HBsAg chronic carriers and 13 had naturally acquired anti-HBs antibodies. The duration of HD treatment was correlated with anti-HCV positivity. A high prevalence of 96.7% (Group 2) was found in patients who underwent more than 5 years of treatment. Our results suggest that anti-HCV core ELISA is more accurate for detecting HCV infection than anti-c100/3. Although the risk associated with the duration of HD treatment and blood transfusion was high, additional factors such as a significant non-transfusional spread of HCV seems to play a role as well. The identification of infective patients by more sensitive methods for HCV genome detection should help to control the transmission of HCV in the unit under study.

HCV; Anti-c100/3; anti-HCV core; Hemodialysis; Aminotransferases; Anti-HBc

Dois grupos de pacientes em tratamento hemodialítico foram avaliados quanto às respostas de anticorpos contra as proteínas não estrutural c100/3 (anti-c100/3) e estrutural core (anti-HCV core) do vírus da hepatite C (HCV). Quarenta e seis pacientes (Grupo 1) nunca apresentaram alterações dos níveis de alanina aminotransferase (ALT) durante o tratamento hemodialítico, ao passo que 52 pacientes (Grupo 2) têm ou já tiveram elevações desta enzima hepática. Em pacientes sem alterações bioquímicas evidentes (Grupo 1) foram encontradas prevalências de 32.6% e 41.3% para anti-c100/3 e anti-HCV core, respectivamente. No Grupo 2, estas prevalências foram de 71,15% e 86,5%. Um teste composto de peptídeos estruturais e não estruturais imobilizados separadamente e dispostos em bandas paralelas em fitas de nailon, foi usado como teste confirmatório. A infecção pelo HBV, avaliada pela presença de anticorpos anti-HBc foi observada em 39.8% dos pacientes; 6 eram portadores crônicos de HBsAg e 13 possuiam anti-HBs adquiridos naturalmente. O tempo de tratamento hemodialítico teve correlação com a positividade para anti-HCV. A prevalência de 96,7% (Grupo 2) foi encontrada em pacientes que tiveram mais de 5 anos de tratamento. Nossos resultados sugerem que o anti-HCV core é um marcador mais preciso para detectar a infecção pelo HCV do que o anti-c100/3. Apesar dos riscos associados com a duração do tratamento e transfusões sanguíneas, uma significante disseminação não transfusional do HCV parece ocorrer dentro da unidade. A identificação de pacientes infectantes por métodos sensíveis como a detecção do genoma viral deverá auxiliar no controle da transmissão do HCV na unidade em estudo.

ORIGINAL ARTICLES

Antibodies against non-structural c100/3 and structural core antigen of hepatitis C virus (HCV) in hemodialysis patients

Anticorpos contra os antígenos não estrutural c100/3 e estrutural core do vírus da hepatite C (HCV) em pacientes de hemodiálise

C.F.T. Yoshida^I; Y. Takahashi^II; B.O.M. Vanderborght^III; C.D. Rouzere^III; M.S. França^I; C. Takahashi^IV; A. Takamizawa^II; I. Yoshida^II; H.G. Schatzmayr^I

^IDepartamento de Virologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil

^IIThe Research Foundation for Microbial Disease of Osaka University, Kanonji, Japan

^IIIInnogenetics, Industriepark, Ghent, Belgium

^IVClínica de Doenças Renais, Rio de Janeiro, Brazil

^{Address for correspondence} Address for correspondence: Clara Fumiko Tachibana Yoshida Departamento de Virologia, Fundação Oswaldo Cruz Av. Brasil, 4365 21040-360. Rio de Janeiro, RJ. Brazil

SUMMARY

Two groups of patients undergoing hemodialysis (HD) maintenance were evaluated for their antibody response to non-structural c100/3 protein and structural core protein of hepatitis C virus (HCV). Forty-six patients (Group 1) never presented liver abnormalities during HD treatment, while 52 patients (Group 2) had either current or prior liver enzyme elevations. Prevalence rates of 32.6% and 41.3% were found for anti-c100/3 and anti-HCV core antibodies, respectively, in patients with silent infections (Group 1). The rate of anti-c100/3 in patients of Group 2 was 71.15% and reached 86.5% for anti-HCV core antibodies. The recognition of anti-c100/3 and anti-core antibodies was significantly higher in Group 2 than in Group 1. A line immunoassay composed of structural and non-structural peptides was used as a confirmation assay. HBV infection, measured by the presence of anti-HBc antibodies, was observed in 39.8% of the patients. Six were HBsAg chronic carriers and 13 had naturally acquired anti-HBs antibodies. The duration of HD treatment was correlated with anti-HCV positivity. A high prevalence of 96.7% (Group 2) was found in patients who underwent more than 5 years of treatment. Our results suggest that anti-HCV core ELISA is more accurate for detecting HCV infection than anti-c100/3. Although the risk associated with the duration of HD treatment and blood transfusion was high, additional factors such as a significant non-transfusional spread of HCV seems to play a role as well. The identification of infective patients by more sensitive methods for HCV genome detection should help to control the transmission of HCV in the unit under study.

Key words: HCV; Anti-c100/3; anti-HCV core; Hemodialysis; Aminotransferases; Anti-HBc.

RESUMO

Dois grupos de pacientes em tratamento hemodialítico foram avaliados quanto às respostas de anticorpos contra as proteínas não estrutural c100/3 (anti-c100/3) e estrutural core (anti-HCV core) do vírus da hepatite C (HCV). Quarenta e seis pacientes (Grupo 1) nunca apresentaram alterações dos níveis de alanina aminotransferase (ALT) durante o tratamento hemodialítico, ao passo que 52 pacientes (Grupo 2) têm ou já tiveram elevações desta enzima hepática. Em pacientes sem alterações bioquímicas evidentes (Grupo 1) foram encontradas prevalências de 32.6% e 41.3% para anti-c100/3 e anti-HCV core, respectivamente. No Grupo 2, estas prevalências foram de 71,15% e 86,5%. Um teste composto de peptídeos estruturais e não estruturais imobilizados separadamente e dispostos em bandas paralelas em fitas de nailon, foi usado como teste confirmatório. A infecção pelo HBV, avaliada pela presença de anticorpos anti-HBc foi observada em 39.8% dos pacientes; 6 eram portadores crônicos de HBsAg e 13 possuiam anti-HBs adquiridos naturalmente. O tempo de tratamento hemodialítico teve correlação com a positividade para anti-HCV. A prevalência de 96,7% (Grupo 2) foi encontrada em pacientes que tiveram mais de 5 anos de tratamento. Nossos resultados sugerem que o anti-HCV core é um marcador mais preciso para detectar a infecção pelo HCV do que o anti-c100/3. Apesar dos riscos associados com a duração do tratamento e transfusões sanguíneas, uma significante disseminação não transfusional do HCV parece ocorrer dentro da unidade. A identificação de pacientes infectantes por métodos sensíveis como a detecção do genoma viral deverá auxiliar no controle da transmissão do HCV na unidade em estudo.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

ACKNOWLEDGEMENTS

We are grateful C.F. Ginuino, L.D. Almeida da Silva, C.R.B. Ferreira and L.A.C. Mercadante for the serology of hepatitis B and the Reagents Section of Biomanguinhos for the supply of hepatitis B kits and anti-human conjugate linked to peroxidase. We also thank A.M.C. Gaspar and F. Ruzany for helpful discussion, Dr. H.G. Pereira for valuable comments and F. Shapiro for review of the manuscript. This work was supported in part by JICA Japan International Cooperation Agency.

Recebido para publicação em 12/11/1992

Aceito para publicação em 23/03/1993

References

1. ALTER, H.J.; PURCELL, R.H.; SHIH, J.W.; MELPOLDER, J.C.; HOUGHTON, M.; CHOO, Q.L. & KUO, G. - Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. New Engl. J. Med., 321: 1494-1500, 1989.
2. BARBARA, J.A. & CONTRERAS, M. - Non-A, non-B hepatitis and the anti-HCV assay. Vox Sang. (Basel), 60: 1-7, 1991.
3. CHIBA, J.; OHBA, H.; MATSUURA, Y.; WATANABE, Y.; KATAYAMA, T.; KIKUCHI, S.; SAITO, I. & MIYAMURA, T. - Serodiagnosis of hepatitis C virus (HCV) infection with an HCV core protein molecularly expressed by a recombinant baculovirus. Proc. nat. Acad. Sci. (Wash.), 88: 4641-4645, 1991.
4. CHOO, Q.L.; KUO, G.; WEINER, A.J.; OVERBY, L.R.; BRADLEY, D.W. & HOUGHTON, M. - Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science, 244: 359-362, 1989.
5. DIENSTAG, J.L. & ALTER, H.J. - Non-A Non-B hepatitis: evolving epidemiological and clinical perspective. Semin. Liver Dis., 6: 67-81, 1986.
6. ESTEBAN, J.I.; ESTEBAN, R.; VILADOMIU, L.; LOPEZ TALAVERA, J.C.; GONZALEZ, A.; HERNANDEZ, J.M.; ROGET, M.; VARGAS, V.; GENESCA, J.; BUTI, M.; GUARDIA, J.; HOUGHTON, M.; CHOO, Q.L. & KUO, G. - Hepatitis C virus antibodies among risk groups in Spain. Lancet, 2: 294-297, 1989.
7. ESTEBAN, J.I.; GONZALEZ, A.; HERNANDEZ, J.M.; VILADOMIU, L.; SANCHEZ, C.; LOPEZ TALAVERA, J.C.; LUCEA, D.; MARTIN VEGA, C.; VIDAL, X.; ESTEBAN, R. & GUARDIA, J. - Evaluation of antibodies to hepatitis C virus in a study of transfusion-associated hepatitis. New Engl. J. Med., 323: 1107-1112, 1990.
8. GILLI, P.; MORETTI, M.; SOFFRITTI, S.; MARCHI, N.; MALACARNE, F.; BEDANI, P.L.; DE PAOLI VITALI, E.; FIOCCHI, O. & MENINI, C. - Non-A, Non-B hepatitis and anti-HCV antibodies in dialysis patients. Int. J. artif. Organs, 13: 737-741, 1990.
9. HARADA, S.; WATANABE, Y.; TAKEUCHI, K.; SUZUKI, T.; KATAYAMA, T.; TAKEBE, Y.; SAITO, I. & MIYAMURA, T. - Expression of processed core protein of hepatitis C virus in mammalian cells. J. Virol., 65: 3015-3021, 1991.
10. HOSEIN, B.; FANG, C.T.; POPOVSKY, M.A.; YE, J.; ZHANG, M. & WANG, C.Y. - Improved serodiagnosis of hepatitis C virus infection with synthetic peptide antigen from capsid protein. Proc. nat. Acad. Sci. (Wash.), 88: 3647-3651, 1991.
11. JEFFERS, L.J.; PEREZ, G.O.; DE MEDINA, M.D.; ORTIZ INTERIAN, C.J.; SCHIFF, E.R.; REDDY, K.R.; JIMENEZ, M.; BOURGOIGNIE, J.J.; VAAMONDE, C.A.; DUNCAN, R.; HOUGHTON, M.; CHOO, Q.L. & KUO, G. - Hepatitis C infection in two urban hemodi-alysis units. Kidney Int., 38: 320-322, 1990.
12. KATO, N.; HIJIKATA, M.; OOTSUYAMA, Y.; NAKAGAWA, M.; OHKOSHI, S.; SUGIMURA, T. & SHIMOTOHNO, K. - Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proc. nat. Acad. Sci. (Wash.), 87: 9524-9528, 1990.
13. KUO, G.; CHOO, Q.L.; ALTER, H.J.; GITNICK, G.L.; REDEKER, A.G.; PURCELL, R.H.; MIYAMURA, T.; DIENSTAG, J.L.; ALTER, M.J.; STEVENS, C.E.; TEGTMEIR, G.E.; BONINO, F.; COLOMBO, M.; LEE, W.S.; BERGER, K.; SCHUSTER, J.R.; OVERBY, L.R.; BRADLEY, D.W. & HOUGHTON, M. - An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science, 244: 362-364, 1989.
14. MATTSSON, L.; ABERG, B.; VON SYDOW, M. & WEILAND, O. - Incidence of hepatitis and seroconversion to hepatitis C virus after open-heart surgery in transfused and non-transfused patients in Sweden. Scand. J. infect. Dis., 23: 25-29, 1991.
15. MONDELLI, M.V.; CRISTINA, G.; FILICI, C.; RONDANELLI, R.G.; PIAZZA, V. & BARBIERI, C. - Anti-HCV positive patients in dialysis units? Lancet, 336: 243-244, 1990.
16. MORTIMER, P.P.; COHEN, B.J.; LITTON, P.A.; VANDERVELDE, E.M.; BASSENDINE, M.F.; BRIND, A.M. & HANBLING, M.H. - Hepatitis C virus antibody. Lancet, 2: 798, 1989.
17. PONZ, E.; CAMPISTOL, J.M.; BARRERA, J.M.; GIL, C.; PINTO, J.; ANDREU, J. & BRUGUERA, M. - Hepatitis C virus antibodies in patients on hemodialysis and after kidney transplantation. Transplant. Proc., 23: 1371-1372, 1991.
18. RUMI, M.G.; COLOMBO, M.; GRINGERI, A. & MANNUCCI, P.M. - High prevalence of antibody to hepatitis C virus in multi-transfused hemophiliacs with normal transaminase levels. Ann. intern. Med., 112: 379-380, 1990.
19. SCHLIPOTTER, U.; ROGGENDORF, M.; ERNST, G.; RASSHOFER, R.; DEINHARDT, F.; WEISE, A.; GLADZIWA, U. & LUZ, N. - Hepatitis C virus antibodies in hemodialysis patients. Lancet, 335: 1409, 1990.
20. SEAWORTH, B.J.; GARRET, L.E.; STEAD, W.W. & HAMILTON, J.D. - NonA, nonB hepatitis in chronic dialysis - Another dilemma. Amer. J. Nephrol., 4: 235-239, 1984.
21. STURM, J.A.; PEREIRA, C.F.A.; SUASSUNA, J.H.R.; NOGUEIRA NETO, J.F.; LOBĂO, V.I.; COELHO, C.J.B.P. & LAURIA, C. - Marcadores virais (vírus B e vírus C) da hepatite em uma unidade de transplante renal. Rev. bras. Pat. clín., 23: 128-135, 1990.
22. TAKAHASHI, C.; YOSHIDA, C.F.T.; GASPAR, A.M.C.; BAPTISTA, M.L.; HOETTE, M. & RUZANY, F. - Ocorręncia das hepatites năoA, năoB em unidade de hemodiálise. Rev. Soc. bras. Med. trop., 21: 105-111, 1988.
23. TAKAHASHI, C.; YOSHIDA, C.F.T.; HOETTE, M.; RUZANY, F. & SCHATZMAYR, H.G. - Prevençăo e controle da hepatite B em unidade de diálise. J. bras. Nefrol., 7: 1-8, 1985.
24. TAKAMIZAWA, A.; MORI, C.; FUKE, I.; MANABE, S.; MURAKAMI, S.; FUJITA, J.; ONISHI, E.; ANDOH, T.; YOSHIDA, I. & OKAYAMA, H. - Structure and organization of the hepatitis C virus genome isolated from human carriers. J. Virol., 65: 1105-1113, 1991.
25. TAKEUCHI, K.; KUBO, Y.; BOONMAR, S.; WATANABE, Y.; KATAYAMA, T.; CHOO, Q.L.; KUO, G.; HOUGHTON, M.; SAITO, I. & MIYAMURA, T. - Nucleotide sequence of core and envelope genes of the hepatitis C virus genome derived directly from human healthy carriers. Nucleic Acids Res., 18: 4626, 1990.
26. VAN DER POEL, C.L.; REESINK, H.W.; LELIE, P.N.; LEENTVAAR KUYPERS, A.; CHOO, Q.L.; KUO, G. & HOUGHTON, M. Anti- hepatitis C antibodies and non-A, non-B post-transfusion hepatitis in The Netherlands. Lancet, 2: 297-298, 1989.
27. WATANABE, Y.; HARADA, S.; SAITO, I. & MIYAMURA, T. - Prevalence of antibody against the core protein of hepatitis C virus in patients with hepatocellular carcinoma. Int. J. Cancer, 48: 340-343, 1991.
28. WONG, D.C.; DIWAN, A.R.; ROSEN, L.; GERIN, J.L.; JOHNSON, R.G.; POLITO, A & PURCELL, R.H. - Non-specificity of anti-HCV test for seroepidemiological analysis. Lancet, 336: 750-751, 1990.
29. YAMAGUCHI, K.; NISHIMURA, C.; FURUOKA, N.; MACHIDA, J.; KUSUMOTO, Y.; FUTAMI, G.; ISHII, T. & TAKATSUKI, K. - Hepatitis C virus antibodies in hemodialysis patients. Lancet, 335: 1409-1410, 1990.
30. YOSHIDA, C.F.; TAKAHASHI, C.; GASPAR, A.M.; SCHATZMAYR, H.G. & RUZANY, F. - Hepatitis C virus in chronic hemodialysis patients with non-A, non-B hepatitis. Nephron, 60: 150-153, 1992.

Address for correspondence:

Clara Fumiko Tachibana Yoshida

Departamento de Virologia, Fundação Oswaldo Cruz

Av. Brasil, 4365

21040-360. Rio de Janeiro, RJ. Brazil

Publication Dates

Publication in this collection
21 July 2006
Date of issue
Aug 1993

History

Received
12 Nov 1992
Accepted
23 Mar 1993

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ALTER, H.J.; PURCELL, R.H.; SHIH, J.W.; MELPOLDER, J.C.; HOUGHTON, M.; CHOO, Q.L. & KUO, G. - Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. New Engl. J. Med., 321: 1494-1500, 1989.

[2] 2. BARBARA, J.A. & CONTRERAS, M. - Non-A, non-B hepatitis and the anti-HCV assay. Vox Sang. (Basel), 60: 1-7, 1991.

[3] 3. CHIBA, J.; OHBA, H.; MATSUURA, Y.; WATANABE, Y.; KATAYAMA, T.; KIKUCHI, S.; SAITO, I. & MIYAMURA, T. - Serodiagnosis of hepatitis C virus (HCV) infection with an HCV core protein molecularly expressed by a recombinant baculovirus. Proc. nat. Acad. Sci. (Wash.), 88: 4641-4645, 1991.

[4] 4. CHOO, Q.L.; KUO, G.; WEINER, A.J.; OVERBY, L.R.; BRADLEY, D.W. & HOUGHTON, M. - Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science, 244: 359-362, 1989.

[5] 5. DIENSTAG, J.L. & ALTER, H.J. - Non-A Non-B hepatitis: evolving epidemiological and clinical perspective. Semin. Liver Dis., 6: 67-81, 1986.

[6] 6. ESTEBAN, J.I.; ESTEBAN, R.; VILADOMIU, L.; LOPEZ TALAVERA, J.C.; GONZALEZ, A.; HERNANDEZ, J.M.; ROGET, M.; VARGAS, V.; GENESCA, J.; BUTI, M.; GUARDIA, J.; HOUGHTON, M.; CHOO, Q.L. & KUO, G. - Hepatitis C virus antibodies among risk groups in Spain. Lancet, 2: 294-297, 1989.

[7] 7. ESTEBAN, J.I.; GONZALEZ, A.; HERNANDEZ, J.M.; VILADOMIU, L.; SANCHEZ, C.; LOPEZ TALAVERA, J.C.; LUCEA, D.; MARTIN VEGA, C.; VIDAL, X.; ESTEBAN, R. & GUARDIA, J. - Evaluation of antibodies to hepatitis C virus in a study of transfusion-associated hepatitis. New Engl. J. Med., 323: 1107-1112, 1990.

[8] 8. GILLI, P.; MORETTI, M.; SOFFRITTI, S.; MARCHI, N.; MALACARNE, F.; BEDANI, P.L.; DE PAOLI VITALI, E.; FIOCCHI, O. & MENINI, C. - Non-A, Non-B hepatitis and anti-HCV antibodies in dialysis patients. Int. J. artif. Organs, 13: 737-741, 1990.

[9] 9. HARADA, S.; WATANABE, Y.; TAKEUCHI, K.; SUZUKI, T.; KATAYAMA, T.; TAKEBE, Y.; SAITO, I. & MIYAMURA, T. - Expression of processed core protein of hepatitis C virus in mammalian cells. J. Virol., 65: 3015-3021, 1991.

[10] 10. HOSEIN, B.; FANG, C.T.; POPOVSKY, M.A.; YE, J.; ZHANG, M. & WANG, C.Y. - Improved serodiagnosis of hepatitis C virus infection with synthetic peptide antigen from capsid protein. Proc. nat. Acad. Sci. (Wash.), 88: 3647-3651, 1991.

[11] 11. JEFFERS, L.J.; PEREZ, G.O.; DE MEDINA, M.D.; ORTIZ INTERIAN, C.J.; SCHIFF, E.R.; REDDY, K.R.; JIMENEZ, M.; BOURGOIGNIE, J.J.; VAAMONDE, C.A.; DUNCAN, R.; HOUGHTON, M.; CHOO, Q.L. & KUO, G. - Hepatitis C infection in two urban hemodi-alysis units. Kidney Int., 38: 320-322, 1990.

[12] 12. KATO, N.; HIJIKATA, M.; OOTSUYAMA, Y.; NAKAGAWA, M.; OHKOSHI, S.; SUGIMURA, T. & SHIMOTOHNO, K. - Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proc. nat. Acad. Sci. (Wash.), 87: 9524-9528, 1990.

[13] 13. KUO, G.; CHOO, Q.L.; ALTER, H.J.; GITNICK, G.L.; REDEKER, A.G.; PURCELL, R.H.; MIYAMURA, T.; DIENSTAG, J.L.; ALTER, M.J.; STEVENS, C.E.; TEGTMEIR, G.E.; BONINO, F.; COLOMBO, M.; LEE, W.S.; BERGER, K.; SCHUSTER, J.R.; OVERBY, L.R.; BRADLEY, D.W. & HOUGHTON, M. - An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science, 244: 362-364, 1989.

[14] 14. MATTSSON, L.; ABERG, B.; VON SYDOW, M. & WEILAND, O. - Incidence of hepatitis and seroconversion to hepatitis C virus after open-heart surgery in transfused and non-transfused patients in Sweden. Scand. J. infect. Dis., 23: 25-29, 1991.

[15] 15. MONDELLI, M.V.; CRISTINA, G.; FILICI, C.; RONDANELLI, R.G.; PIAZZA, V. & BARBIERI, C. - Anti-HCV positive patients in dialysis units? Lancet, 336: 243-244, 1990.

[16] 16. MORTIMER, P.P.; COHEN, B.J.; LITTON, P.A.; VANDERVELDE, E.M.; BASSENDINE, M.F.; BRIND, A.M. & HANBLING, M.H. - Hepatitis C virus antibody. Lancet, 2: 798, 1989.

[17] 17. PONZ, E.; CAMPISTOL, J.M.; BARRERA, J.M.; GIL, C.; PINTO, J.; ANDREU, J. & BRUGUERA, M. - Hepatitis C virus antibodies in patients on hemodialysis and after kidney transplantation. Transplant. Proc., 23: 1371-1372, 1991.

[18] 18. RUMI, M.G.; COLOMBO, M.; GRINGERI, A. & MANNUCCI, P.M. - High prevalence of antibody to hepatitis C virus in multi-transfused hemophiliacs with normal transaminase levels. Ann. intern. Med., 112: 379-380, 1990.

[19] 19. SCHLIPOTTER, U.; ROGGENDORF, M.; ERNST, G.; RASSHOFER, R.; DEINHARDT, F.; WEISE, A.; GLADZIWA, U. & LUZ, N. - Hepatitis C virus antibodies in hemodialysis patients. Lancet, 335: 1409, 1990.

[20] 20. SEAWORTH, B.J.; GARRET, L.E.; STEAD, W.W. & HAMILTON, J.D. - NonA, nonB hepatitis in chronic dialysis - Another dilemma. Amer. J. Nephrol., 4: 235-239, 1984.

[21] 21. STURM, J.A.; PEREIRA, C.F.A.; SUASSUNA, J.H.R.; NOGUEIRA NETO, J.F.; LOBĂO, V.I.; COELHO, C.J.B.P. & LAURIA, C. - Marcadores virais (vírus B e vírus C) da hepatite em uma unidade de transplante renal. Rev. bras. Pat. clín., 23: 128-135, 1990.

[22] 22. TAKAHASHI, C.; YOSHIDA, C.F.T.; GASPAR, A.M.C.; BAPTISTA, M.L.; HOETTE, M. & RUZANY, F. - Ocorręncia das hepatites năoA, năoB em unidade de hemodiálise. Rev. Soc. bras. Med. trop., 21: 105-111, 1988.

[23] 23. TAKAHASHI, C.; YOSHIDA, C.F.T.; HOETTE, M.; RUZANY, F. & SCHATZMAYR, H.G. - Prevençăo e controle da hepatite B em unidade de diálise. J. bras. Nefrol., 7: 1-8, 1985.

[24] 24. TAKAMIZAWA, A.; MORI, C.; FUKE, I.; MANABE, S.; MURAKAMI, S.; FUJITA, J.; ONISHI, E.; ANDOH, T.; YOSHIDA, I. & OKAYAMA, H. - Structure and organization of the hepatitis C virus genome isolated from human carriers. J. Virol., 65: 1105-1113, 1991.

[25] 25. TAKEUCHI, K.; KUBO, Y.; BOONMAR, S.; WATANABE, Y.; KATAYAMA, T.; CHOO, Q.L.; KUO, G.; HOUGHTON, M.; SAITO, I. & MIYAMURA, T. - Nucleotide sequence of core and envelope genes of the hepatitis C virus genome derived directly from human healthy carriers. Nucleic Acids Res., 18: 4626, 1990.

[26] 26. VAN DER POEL, C.L.; REESINK, H.W.; LELIE, P.N.; LEENTVAAR KUYPERS, A.; CHOO, Q.L.; KUO, G. & HOUGHTON, M. Anti- hepatitis C antibodies and non-A, non-B post-transfusion hepatitis in The Netherlands. Lancet, 2: 297-298, 1989.

[27] 27. WATANABE, Y.; HARADA, S.; SAITO, I. & MIYAMURA, T. - Prevalence of antibody against the core protein of hepatitis C virus in patients with hepatocellular carcinoma. Int. J. Cancer, 48: 340-343, 1991.

[28] 28. WONG, D.C.; DIWAN, A.R.; ROSEN, L.; GERIN, J.L.; JOHNSON, R.G.; POLITO, A & PURCELL, R.H. - Non-specificity of anti-HCV test for seroepidemiological analysis. Lancet, 336: 750-751, 1990.

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