Autoantibodies before, during and after administration of recombinant interferon-alpha for chronic viral hepatitis

Lopes, Edmundo P.A.; Silva, A. Eduardo; Sette Junior, Hoel; Guimarães, Rubens X.; Ferraz, M. Lucia

doi:10.1590/S0036-46651995000500012

Abstract

This study was undertaken to investigate the presence of autoantibodies in patients with chronic viral hepatitis B and C, before, during and after interferon-alpha (IFN-alpha) therapy and to study their relation to dose and type of IFN-alpha and response to treatment. Fifty patients with chronic hepatitis were divided in two groups, a control-group of 21 patients (10 type B and 11 type C) who were followed for 6 months without treatment and an IFN-group consisting of 29 patients (8 type B and 21 type C) who received IFN therapy for 6 months. Serum samples were tested for a range of antibodies at the start of the study, during therapy and at the end of the 6 month period. Antibodies tested for included: antinuclear, smooth muscle, antimitochondrial, parietal cell and thyroid microsomal. Four (8%) of the total patient group had autoantibodies at the beginning of the study (two in each group). During the follow-up period no patient in the control group developed antibodies compared with 3 (11%) patients in the treatment group. Autoantibodies developed in patients treated with higher doses of IFN and were found in those patients who tended to show a poor response to IFN-therapy. Further studies are needed to establish the relationship between poor response to IFN-alpha and development of autoantibodies.

Viral hepatitis; Autoantibodies; Interferon-alpha

Resumo

Este estudo teve como objetivo avaliar a presença de auto-anticorpos em pacientes com hepatite crônica pelos vírus B e C, antes, durante e após tratamento com interferon-alfa (IFN-alfa), assim como estudar a relação destes anticorpos com o tipo de IFN, com a dose e com a resposta terapêutica. Cinqüenta pacientes com hepatite viral crônica foram divididos em 2 grupos: grupo-controle constituído por 21 pacientes (10 hepatites B e 11 hepatites C), que foram seguidos durante 6 meses sem tratamento e grupo-IFN constituído por 29 pacientes (8 hepatites B e 21 hepatites C), que receberam IFN-alfa durante 6 meses. Anticorpos antinúcleo, antimúsculo liso, antimitocôndria, anticélula parietal e antitireóide foram pesquisados em amostras de soro colhidas antes do início, durante e ao final do estudo. Quatro dos 50 pacientes (8%) apresentavam auto-anticorpos no início do estudo (2 em cada grupo). Durante o estudo nenhum paciente do grupo-controle desenvolveu auto-anticorpos, enquanto que 3 (11%) pacientes do grupo-IFN passaram a apresentá-los. Os auto-anticorpos ocorreram apenas em pacientes tratados com doses mais elevadas de IFN. Verificou-se ainda tendência à resposta desfavorável ao tratamento naqueles indivíduos que apresentaram ou desenvolveram auto-anticorpos. Assim, sugere-se que mais estudos sejam realizados para determinar se existe ou não relação entre resposta desfavorável e a presença ou o desenvolvimento de auto-anticorpos.

CLINICAL AND LABORATORIAL STUDIES

Autoantibodies before, during and after administration of recombinant interferon-a for chronic viral hepatitis

Estudo dos auto-anticorpos nas Hepatites virais crônicas B e C antes, durante e após tratamento com Interferon-a

Edmundo P.A. Lopes^I; A. Eduardo Silva^I; Hoel Sette Junior^II; Rubens X. Guimarães^I; M. Lucia Ferraz^I

^IDisciplina de Gastroenterologia, Escola Paulista de Medicina, São Paulo, S.P., Brasil

^IIHospital Oswaldo Cruz, São Paulo, SP, Brasil

Correspondence to

SUMMARY

This study was undertaken to investigate the presence of autoantibodies in patients with chronic viral hepatitis B and C, before, during and after interferon-a (IFN-a) therapy and to study their relation to dose and type of IFN-a and response to treatment. Fifty patients with chronic hepatitis were divided in two groups, a control-group of 21 patients (10 type B and 11 type C) who were followed for 6 months without treatment and an IFN-group consisting of 29 patients (8 type B and 21 type C) who received IFN therapy for 6 months. Serum samples were tested for a range of antibodies at the start of the study, during therapy and at the end of the 6 month period. Antibodies tested for included: antinuclear, smooth muscle, antimitochondrial, parietal cell and thyroid microsomal. Four (8%) of the total patient group had autoantibodies at the beginning of the study (two in each group). During the follow-up period no patient in the control group developed antibodies compared with 3 (11%) patients in the treatment group. Autoantibodies developed in patients treated with higher doses of IFN and were found in those patients who tended to show a poor response to IFN-therapy. Further studies are needed to establish the relationship between poor response to IFN-a and development of autoantibodies.

Keywords: Viral hepatitis; Autoantibodies; Interferon-a

RESUMO

Este estudo teve como objetivo avaliar a presença de auto-anticorpos em pacientes com hepatite crônica pelos vírus B e C, antes, durante e após tratamento com interferon-a (IFN-a), assim como estudar a relação destes anticorpos com o tipo de IFN, com a dose e com a resposta terapêutica. Cinqüenta pacientes com hepatite viral crônica foram divididos em 2 grupos: grupo-controle constituído por 21 pacientes (10 hepatites B e 11 hepatites C), que foram seguidos durante 6 meses sem tratamento e grupo-IFN constituído por 29 pacientes (8 hepatites B e 21 hepatites C), que receberam IFN-a durante 6 meses. Anticorpos antinúcleo, antimúsculo liso, antimitocôndria, anticélula parietal e antitireóide foram pesquisados em amostras de soro colhidas antes do início, durante e ao final do estudo. Quatro dos 50 pacientes (8%) apresentavam auto-anticorpos no início do estudo (2 em cada grupo). Durante o estudo nenhum paciente do grupo-controle desenvolveu auto-anticorpos, enquanto que 3 (11%) pacientes do grupo-IFN passaram a apresentá-los. Os auto-anticorpos ocorreram apenas em pacientes tratados com doses mais elevadas de IFN. Verificou-se ainda tendência à resposta desfavorável ao tratamento naqueles indivíduos que apresentaram ou desenvolveram auto-anticorpos. Assim, sugere-se que mais estudos sejam realizados para determinar se existe ou não relação entre resposta desfavorável e a presença ou o desenvolvimento de auto-anticorpos.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

Recebido para publicação em 24/01/1995

Aceito para publicação em 16/10/1995

References

1. BRADLEY, D.W. - Virology, molecular biology, and serology of hepatitis C virus. Transf. Med. Rev., 6: 93-102, 1992.
2. CALZIA, R.; MIGLIORINI, R.; BADARACCO, B. et al. - Development of autoantibodies during IFN-a2r treatment in chronic viral hepatitis. J. Hepat., 17 (suppl. 1): S37, 1992.
3. DI BISCEGLIE, A.M.; GOODMAN, Z.D.; ISHAK, K.G. et al. - Long-term clinical and histopathological follow-up of chronic post-transfusion hepatitis. Hepatology, 14: 969-974, 1991.
4. DIANZANI, F. & ANTONELLI, G. - Physiological mechanisms of production and action of interferon in response to viral infection. Advanc. exp. Med. Biol., 257: 47-60, 1989.
5. FATTOVICH, G.; BETTERLE, C.; BROLLO, L. et al. - Autoantibodies during a-interferon therapy for chronic hepatitis B. J. Med. Virol., 34: 132-135, 1991.
6. FATTOVICH, G.; BROLLO, L.; GIUSTINA, G. et al. - Natural history and prognostic factors for chronic hepatitis type B. Gut, 32: 294-298, 1991.
7. FINDOR, J.A.; IGARTUA, E.; SORDÁ, J. et al. - Circulating autoantibodies after treatment with recombinant (a) interferon 2b (IFN 2b). Acta Hepat., 1: 73, 1991.
8. FRIED, M.W.; DRAGUESKU, J.O.; SHINDO, M. et al. - Clinical and serological differentiation of autoimmune and hepatitis C virus-related chronic hepatitis. Dig. Dis. Sci., 38: 631-636, 1993.
9. KANEKO, S., MILLER, R.H.; FEINSTONE, S.M. et al. - Detection of serum hepatitis B virus DNA in patients with chronic hepatitis using the polymerase chain reaction assay. Proc. nat. Acad. Sci. (Wash.), 86: 312-316, 1989.
10. KOIVISTO, V.A.; PELKONEN, R. & CANTELL, K. - Effect of interferon on glucose tolerance and insulin sensitivity. Diabetes, 38: 641-647, 1989.
11. KORENMAN, J.; BAKER, B.; WAGGNOER, J. et al. - Long-term remission of chronic hepatitis B after alpha-interferon therapy. Ann. intern. Med., 114: 629-634, 1991.
12. LISKER-MELMAN, M.; DI BISCEGLIE, A.M.; USALA, S.J. et al. - Development of thyroid disease during therapy of chronic viral hepatitis with interferon alpha. Gastroenterology, 102: 2155-2160, 1992.
13. LOPES, E.P.A.; OLIVEIRA, P.M.; SILVA, A.E. et al. - Exacerbation of type 2 diabetes mellitus during interferon-alfa therapy for chronic hepatitis B. Lancet, 343: 244, 1994.
14. MAYET, W-J.; HESS, G.; GERKEN, G. et al. - Treatment of chronic type B hepatitis with recombinant a-interferon induces autoantibodies not specific for autoimmune chronic hepatitis. Hepatology, 10: 24-28, 1989.
15. OKUNO, T.; SHINDO, M.; ARAI, K. et al - Autoantibodies related to interferon therapy in chronic hepatitis B may affect the therapeutic response to interferon. Nippon Shokakibyo Gakkay Zasshi, 88: 2771-2777, 1991.
16. PÉREZ, R.; PRAVIA, R.; LINARES, A. et al. - Response related factors in recombinant interferon alfa-2b treatment of chronic hepatitis C. Gut, 34 (suppl.2): S139-S140, 1993.
17. RENAULT, P.F. & HOOFNAGLE, J. H. - Side effects of alpha Ąnterferon. Semin. Liver Dis., 9: 273-278, 1989.
18. SARACCO, G.; TOUSCOZ, A.; DURAZZO, M. et al. - Autoantibodies and response to a-interferon with in patients with chronic viral hepatitis. J. Hepat., 11: 339-343, 1990.
19. SHINDO, M.; BISCEGLIE, A.M. & HOOFNAGLE, J.H. - Long-term follow-up of patients with chronic hepatitis C treated with a-interferon. Hepatology, 15: 1013-1016, 1992.
20. THOMAS, H.C. - The hepatitis B virus and the host response. J. Hepat, 11 (suppl. 1): S83-S89, 1990.
21. TODD, J.A.; ACHA-ORBEA, H.; BELL, J. et al. - A molecular basis of MHC class II-associated autoimmunity. Science, 240: 1003-1009, 1988.
22. TRAN, A.; QUARANTA, J-F.; BENZAKEN, S. et al. - High prevalence of thyroid autoantibodies in a prospective series of patients with chronic hepatitis C before interferon therapy. Hepatology, 18: 253-257, 1993.
23. WEBER, P.; WIEDMANN, K-H.; KLEIN, R. et al. - Induction of autoimmune phenomena in patients with chronic hepatitis B treated with gamma-interferon. J. Hepat., 20: 321-328, 1994.

Correspondence to:

M. Lucia Ferraz, M.D.

Rua Machado Bittencourt, 413/81

04043-002 São Paulo, SP, Brasil

Fax: 55-11-572-5945

Publication Dates

Publication in this collection
21 Sept 2006
Date of issue
Oct 1995

History

Accepted
16 Oct 1995
Received
24 Jan 1995

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

[1] 1. BRADLEY, D.W. - Virology, molecular biology, and serology of hepatitis C virus. Transf. Med. Rev., 6: 93-102, 1992.

[2] 2. CALZIA, R.; MIGLIORINI, R.; BADARACCO, B. et al. - Development of autoantibodies during IFN-a2r treatment in chronic viral hepatitis. J. Hepat., 17 (suppl. 1): S37, 1992.

[3] 3. DI BISCEGLIE, A.M.; GOODMAN, Z.D.; ISHAK, K.G. et al. - Long-term clinical and histopathological follow-up of chronic post-transfusion hepatitis. Hepatology, 14: 969-974, 1991.

[4] 4. DIANZANI, F. & ANTONELLI, G. - Physiological mechanisms of production and action of interferon in response to viral infection. Advanc. exp. Med. Biol., 257: 47-60, 1989.

[5] 5. FATTOVICH, G.; BETTERLE, C.; BROLLO, L. et al. - Autoantibodies during a-interferon therapy for chronic hepatitis B. J. Med. Virol., 34: 132-135, 1991.

[6] 6. FATTOVICH, G.; BROLLO, L.; GIUSTINA, G. et al. - Natural history and prognostic factors for chronic hepatitis type B. Gut, 32: 294-298, 1991.

[7] 7. FINDOR, J.A.; IGARTUA, E.; SORDÁ, J. et al. - Circulating autoantibodies after treatment with recombinant (a) interferon 2b (IFN 2b). Acta Hepat., 1: 73, 1991.

[8] 8. FRIED, M.W.; DRAGUESKU, J.O.; SHINDO, M. et al. - Clinical and serological differentiation of autoimmune and hepatitis C virus-related chronic hepatitis. Dig. Dis. Sci., 38: 631-636, 1993.

[9] 9. KANEKO, S., MILLER, R.H.; FEINSTONE, S.M. et al. - Detection of serum hepatitis B virus DNA in patients with chronic hepatitis using the polymerase chain reaction assay. Proc. nat. Acad. Sci. (Wash.), 86: 312-316, 1989.

[10] 10. KOIVISTO, V.A.; PELKONEN, R. & CANTELL, K. - Effect of interferon on glucose tolerance and insulin sensitivity. Diabetes, 38: 641-647, 1989.

[11] 11. KORENMAN, J.; BAKER, B.; WAGGNOER, J. et al. - Long-term remission of chronic hepatitis B after alpha-interferon therapy. Ann. intern. Med., 114: 629-634, 1991.

[12] 12. LISKER-MELMAN, M.; DI BISCEGLIE, A.M.; USALA, S.J. et al. - Development of thyroid disease during therapy of chronic viral hepatitis with interferon alpha. Gastroenterology, 102: 2155-2160, 1992.

[13] 13. LOPES, E.P.A.; OLIVEIRA, P.M.; SILVA, A.E. et al. - Exacerbation of type 2 diabetes mellitus during interferon-alfa therapy for chronic hepatitis B. Lancet, 343: 244, 1994.

[14] 14. MAYET, W-J.; HESS, G.; GERKEN, G. et al. - Treatment of chronic type B hepatitis with recombinant a-interferon induces autoantibodies not specific for autoimmune chronic hepatitis. Hepatology, 10: 24-28, 1989.

[15] 15. OKUNO, T.; SHINDO, M.; ARAI, K. et al - Autoantibodies related to interferon therapy in chronic hepatitis B may affect the therapeutic response to interferon. Nippon Shokakibyo Gakkay Zasshi, 88: 2771-2777, 1991.

[16] 16. PÉREZ, R.; PRAVIA, R.; LINARES, A. et al. - Response related factors in recombinant interferon alfa-2b treatment of chronic hepatitis C. Gut, 34 (suppl.2): S139-S140, 1993.

[17] 17. RENAULT, P.F. & HOOFNAGLE, J. H. - Side effects of alpha Ąnterferon. Semin. Liver Dis., 9: 273-278, 1989.

[18] 18. SARACCO, G.; TOUSCOZ, A.; DURAZZO, M. et al. - Autoantibodies and response to a-interferon with in patients with chronic viral hepatitis. J. Hepat., 11: 339-343, 1990.

[19] 19. SHINDO, M.; BISCEGLIE, A.M. & HOOFNAGLE, J.H. - Long-term follow-up of patients with chronic hepatitis C treated with a-interferon. Hepatology, 15: 1013-1016, 1992.

[20] 20. THOMAS, H.C. - The hepatitis B virus and the host response. J. Hepat, 11 (suppl. 1): S83-S89, 1990.

[21] 21. TODD, J.A.; ACHA-ORBEA, H.; BELL, J. et al. - A molecular basis of MHC class II-associated autoimmunity. Science, 240: 1003-1009, 1988.

[22] 22. TRAN, A.; QUARANTA, J-F.; BENZAKEN, S. et al. - High prevalence of thyroid autoantibodies in a prospective series of patients with chronic hepatitis C before interferon therapy. Hepatology, 18: 253-257, 1993.

[23] 23. WEBER, P.; WIEDMANN, K-H.; KLEIN, R. et al. - Induction of autoimmune phenomena in patients with chronic hepatitis B treated with gamma-interferon. J. Hepat., 20: 321-328, 1994.