Long term follow-up and patterns of response of ALT in patients with chronic hepatitis NANB/C treated with recombinant interferon-alpha

Silva, L.C. da; Ono, S.K.; Fonseca, L.E.P.; Carrilho, F.J.; Mendes, L.C.A.; França, A.V.C.; Madruga, C.L.A.; Laudanna, A.A.

doi:10.1590/S0036-46651995000300010

Abstracts

The response to interferon treatment in chronic hepatitis NANB/C has usually been classified as complete, partial or absent, according to the behavior of serum alanine aminotransferase (ALT). However, a more detailed observation of the enzymatic activity has shown that the patterns may be more complex. The aim of this study was to describe the long term follow-up and patterns of ALT response in patients with chronic hepatitis NANB/C treated with recombinant interferon-alpha. A follow-up of 6 months or more after interferon-a was achieved in 44 patients. We have classified the serum ALT responses into six patterns and the observed frequencies were as follows: I. Long term response = 9 (20.5%); II. Normalization followed by persistent relapse after IFN = 7 (15.9%); III. Normalization with transient relapse = 5 (11.9%); IV. Temporary normalization and relapse during IFN = 4 (9.1%); V. Partial response (more than 50% of ALT decrease) = 7 (15.9%); VI. No response = 12 (27.3%). In conclusion, ALT patterns vary widely during and after IFN treatment and can be classified in at least 6 types.

Chronic hepatitis; Hepatitis C; Antiviral Therapy; Interferon; Response; Relapse

A resposta ao tratamento com interferon em pacientes com hepatite crônica NANB/C tem sido classificada como completa, parcial ou ausente, de acordo com o comportamento da alanino aminotransferase sérica (ALT). Entretanto, uma observação mais detalhada da atividade enzimática tem mostrado que os padrões podem ser mais complexos. O objetivo deste estudo foi descrever o seguimento tardio e os padrões de resposta da ALT em pacientes com hepatite crônica NANB/C tratados com interferon alfa recombinante. Classificamos os tipos de resposta da ALT em 6 padrões e as freqüências observadas foram:I. Resposta completa e persistente = 9 (20,5%); II. Resposta completa com recaída persistente após o IFN = 7 (15,9%); III. Resposta completa com recaída temporária = 5 (11,9%); IV. Normalização temporária e recaída durante o tratamento com IFN = 4 (9,1%); V. Resposta parcial (queda dos níveis iniciais da ALT maior que 50%) = 7 (15,9%); VI. Não resposta = 12 (27,3%). Em conclusão, os padrões de ALT variam durante e após o tratamento e podem ser classificados em pelo menos 6 tipos.

CLINICAL STUDIES

Long term follow-up and patterns of response of ALT in patients with chronic hepatitis NANB/C treated with recombinant interferon-a

Seguimento tardio e padrões de resposta da ALT em pacientes com hepatite crônica NANB/C tratados com interferon-a

L.C. da Silva; S.K. Ono; L.E.P. Fonseca; F.J. Carrilho; L.C.A. Mendes; A.V.C. França; C.L.A. Madruga; A.A. Laudanna

Departament of Gastroenterology - Hepatology branch, University of São Paulo, School of Medicine; Institute of Tropical Medicine (LIM-47) São Paulo, SP, Brazil

^{Correspondence to} Correspondence to: Prof. Luiz Caetano da Silva Instituto de Medicina Tropical Av. Dr. Enéas de Carvalho Aguiar, 470 05403-000 São Paulo, SP, Brasil Telephone number: (011) 883-3233 ramal 328

SUMMARY

The response to interferon treatment in chronic hepatitis NANB/C has usually been classified as complete, partial or absent, according to the behavior of serum alanine aminotransferase (ALT). However, a more detailed observation of the enzymatic activity has shown that the patterns may be more complex. The aim of this study was to describe the long term follow-up and patterns of ALT response in patients with chronic hepatitis NANB/C treated with recombinant interferon-a. A follow-up of 6 months or more after interferon-a was achieved in 44 patients. We have classified the serum ALT responses into six patterns and the observed frequencies were as follows: I. Long term response = 9 (20.5%); II. Normalization followed by persistent relapse after IFN = 7 (15.9%); III. Normalization with transient relapse = 5 (11.9%); IV. Temporary normalization and relapse during IFN = 4 (9.1%); V. Partial response (more than 50% of ALT decrease) = 7 (15.9%); VI. No response = 12 (27.3%). In conclusion, ALT patterns vary widely during and after IFN treatment and can be classified in at least 6 types.

Keywords: Chronic hepatitis; Hepatitis C; Antiviral Therapy; Interferon; Response; Relapse.

RESUMO

A resposta ao tratamento com interferon em pacientes com hepatite crônica NANB/C tem sido classificada como completa, parcial ou ausente, de acordo com o comportamento da alanino aminotransferase sérica (ALT). Entretanto, uma observação mais detalhada da atividade enzimática tem mostrado que os padrões podem ser mais complexos. O objetivo deste estudo foi descrever o seguimento tardio e os padrões de resposta da ALT em pacientes com hepatite crônica NANB/C tratados com interferon alfa recombinante. Classificamos os tipos de resposta da ALT em 6 padrões e as freqüências observadas foram:I. Resposta completa e persistente = 9 (20,5%); II. Resposta completa com recaída persistente após o IFN = 7 (15,9%); III. Resposta completa com recaída temporária = 5 (11,9%); IV. Normalização temporária e recaída durante o tratamento com IFN = 4 (9,1%); V. Resposta parcial (queda dos níveis iniciais da ALT maior que 50%) = 7 (15,9%); VI. Não resposta = 12 (27,3%). Em conclusão, os padrões de ALT variam durante e após o tratamento e podem ser classificados em pelo menos 6 tipos.

Full text available only in PDF format.

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ACKNOWLEDGEMENT

The authors would like to thank Dr. Marcos Wolff for reading this manuscript and making a number of valuable suggestions. Dr. S.K. Ono was a recipient of a grant supported by Schering-Plough Laboratories.

Recebido para publicação em 26/12/1994.

Aceito para publicação em 07/03/1995.

List of abbreviations: IFN Interferon; ALT Alamineaminotransferase; NANB/C Non A- Non B/C; CH-C Chronic hepatitis C; HCV Hepatitis C virus and PCR Polymerase chain reaction.

1. ALBERTI, A.; CHEMELLO, L.; BONETTI, P. et al. - Treatment with interferon(s) of community-acquired chronic hepatitis and cirrhosis type C. J. Hepat., 17 (suppl. 3): S123-S126, 1993.
2. BONINO, F.; BRUNETTO, M.R.; NEGRO, F. et al. - Hepatitis C virus infection and disease. Diagnostic problems. J. Hepat., 17 (suppl. 3): S78-S82, 1993.
3. DAVIS, G.L.; BALART, L.A.; SCHIFF, E.R. et al. - Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. New Engl. J. Med., 321: 1501-1506, 1989.
4. DOUGLAS, D.D.; RAKELA, J.; LIN, H.J. et al. - Randomized controlled trial of recombinant alpha-2a-interferon for chronic hepatitis C. Comparison of alanine aminotransferase normalization versus loss of HCV RNA and anti-HCV IgM. Dig. Dis. Sci., 38: 601-607, 1993.
5. FARCI, P.; ALTER, H.J.; GOVINDARANJAN, S. et al. - Lack of protective immunity against reinfection with hepatitis C virus. Science, 258: 135-140, 1992.
6. FONSECA, L.E.P. da. - Tratamento da hepatite crônica năo-A, năo-B com interferon - alfa recombinante. Săo Paulo 1992. (Dissertaçăo de mestrado - Faculdade de Medicina da Universidade de Săo Paulo).
7. HOOFNAGLE, J.H. - Treatment. In: ZUCKERMAN, A.J. & THOMAS, H.C. Viral hepatitis. Scientific basis and clinical management. Edinburgh, Churchill Livingstone, 1993. p. 307.
8. HOOFNAGLE, J.H.; DI BISCEGLIE, A.M. & SHINDO, M. - Antiviral therapy of hepatitis C - present and future. J. Hepat., 17 (suppl. 3): S130-S136, 1993.
9. UNO, S.; HINO, K.; KUROKI, T.; SUZUKI, H. & YAMAMOTO, S. - Treatment of chronic hepatitis C with high-dose Interferon a-2b. A multicenter study. Dig. Dis. Sci., 38: 612-618, 1993.
10. JOUET, P.; ROUDOT-THOROVAL, F.; DHUMEAUX, D.; MÉTREAU, J.M. & Le Group Français pour létude du traitment des hépatites chroniques NANB/C - Comparative efficacy of interferon alfa in cirrhotic and noncirrhotic patients with non-A, non-B, C hepatitis. Gastroenterology, 106: 686-690, 1994.
11. MILLELA, M.; ANTONELLI, G.; SANTANTONIO, T. et al. - Neutralizing antibodies to recombinant alpha-interferon and response to therapy in chronic hepatitis C virus infection. Liver, 13: 146-150, 1993.
12. ONO, S.K.; MENDES, L.C.A.; DA SILVA, L.C. et al. - Cocaína como causa de "recaída" após interferon alfa recombinante (IFN) na hepatite C. In: CONGRESSO BRASILEIRO DE GASTROENTEROLOGIA., 33, Porto Alegre, 20-23 de novembro de 1994.
13. ORITO, E.; MIZOKAMI, M.; MIZOGUCHI, N. et al. - Hepatitis C virus serotype II responds more favorably to interferon-a therapy. J. Hepat., 21: 130-132, 1994.
14. PAPO, T.; MERCELLIN, P.; BERNUAU, J. et al. - Autoimmune chronic hepatitis exacerbated by Alpha-interferon. Ann. intern. Med., 116: 51-53, 1992.
15. QU, D.; LI, J.S.; VITVITSKI, L. et al. - Hepatitis C virus genotypes in France: comparison of clinical features of patients infected with HCV type I and type II. J. Hepat., 21: 70-75, 1994.
16. SERFATY, L.; GIRAL, P.; LORIA, A. et al. - Factors predictive of the response to interferon in patients with chronic hepatitis C. J. Hepat., 21: 12-17, 1994.
17. SHAPIRO, A. - Long term surveillance of HIV, HBV and HCV infected patients. Ann. Hematol., 68: S87-S88, 1994.
18. VAN THIEL, D.H.; FRIEDLANDER, L.; FAGIUOLI, S. et al. - Response to interferon a therapy is influenced by the iron content of the liver. J. Hepat., 20: 410-415, 1994.
19. YOSHIOKA, K.; KAKAMU, S.; AIYAMA, T. - Detection of serum antibodies to E2/NS1 hypervariable region of hepatitis C virus. Hepatology, 20: 231A, 1994.

Correspondence to:

Prof. Luiz Caetano da Silva

Instituto de Medicina Tropical

Av. Dr. Enéas de Carvalho Aguiar, 470

05403-000 São Paulo, SP, Brasil

Telephone number: (011) 883-3233 ramal 328

Publication Dates

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

History

Received
26 Dec 1994
Accepted
07 Mar 1995

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

[1] 1. ALBERTI, A.; CHEMELLO, L.; BONETTI, P. et al. - Treatment with interferon(s) of community-acquired chronic hepatitis and cirrhosis type C. J. Hepat., 17 (suppl. 3): S123-S126, 1993.

[2] 2. BONINO, F.; BRUNETTO, M.R.; NEGRO, F. et al. - Hepatitis C virus infection and disease. Diagnostic problems. J. Hepat., 17 (suppl. 3): S78-S82, 1993.

[3] 3. DAVIS, G.L.; BALART, L.A.; SCHIFF, E.R. et al. - Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. New Engl. J. Med., 321: 1501-1506, 1989.

[4] 4. DOUGLAS, D.D.; RAKELA, J.; LIN, H.J. et al. - Randomized controlled trial of recombinant alpha-2a-interferon for chronic hepatitis C. Comparison of alanine aminotransferase normalization versus loss of HCV RNA and anti-HCV IgM. Dig. Dis. Sci., 38: 601-607, 1993.

[5] 5. FARCI, P.; ALTER, H.J.; GOVINDARANJAN, S. et al. - Lack of protective immunity against reinfection with hepatitis C virus. Science, 258: 135-140, 1992.

[6] 6. FONSECA, L.E.P. da. - Tratamento da hepatite crônica năo-A, năo-B com interferon - alfa recombinante. Săo Paulo 1992. (Dissertaçăo de mestrado - Faculdade de Medicina da Universidade de Săo Paulo).

[7] 7. HOOFNAGLE, J.H. - Treatment. In: ZUCKERMAN, A.J. & THOMAS, H.C. Viral hepatitis. Scientific basis and clinical management. Edinburgh, Churchill Livingstone, 1993. p. 307.

[8] 8. HOOFNAGLE, J.H.; DI BISCEGLIE, A.M. & SHINDO, M. - Antiviral therapy of hepatitis C - present and future. J. Hepat., 17 (suppl. 3): S130-S136, 1993.

[9] 9. UNO, S.; HINO, K.; KUROKI, T.; SUZUKI, H. & YAMAMOTO, S. - Treatment of chronic hepatitis C with high-dose Interferon a-2b. A multicenter study. Dig. Dis. Sci., 38: 612-618, 1993.

[10] 10. JOUET, P.; ROUDOT-THOROVAL, F.; DHUMEAUX, D.; MÉTREAU, J.M. & Le Group Français pour létude du traitment des hépatites chroniques NANB/C - Comparative efficacy of interferon alfa in cirrhotic and noncirrhotic patients with non-A, non-B, C hepatitis. Gastroenterology, 106: 686-690, 1994.

[11] 11. MILLELA, M.; ANTONELLI, G.; SANTANTONIO, T. et al. - Neutralizing antibodies to recombinant alpha-interferon and response to therapy in chronic hepatitis C virus infection. Liver, 13: 146-150, 1993.

[12] 12. ONO, S.K.; MENDES, L.C.A.; DA SILVA, L.C. et al. - Cocaína como causa de "recaída" após interferon alfa recombinante (IFN) na hepatite C. In: CONGRESSO BRASILEIRO DE GASTROENTEROLOGIA., 33, Porto Alegre, 20-23 de novembro de 1994.

[13] 13. ORITO, E.; MIZOKAMI, M.; MIZOGUCHI, N. et al. - Hepatitis C virus serotype II responds more favorably to interferon-a therapy. J. Hepat., 21: 130-132, 1994.

[14] 14. PAPO, T.; MERCELLIN, P.; BERNUAU, J. et al. - Autoimmune chronic hepatitis exacerbated by Alpha-interferon. Ann. intern. Med., 116: 51-53, 1992.

[15] 15. QU, D.; LI, J.S.; VITVITSKI, L. et al. - Hepatitis C virus genotypes in France: comparison of clinical features of patients infected with HCV type I and type II. J. Hepat., 21: 70-75, 1994.

[16] 16. SERFATY, L.; GIRAL, P.; LORIA, A. et al. - Factors predictive of the response to interferon in patients with chronic hepatitis C. J. Hepat., 21: 12-17, 1994.

[17] 17. SHAPIRO, A. - Long term surveillance of HIV, HBV and HCV infected patients. Ann. Hematol., 68: S87-S88, 1994.

[18] 18. VAN THIEL, D.H.; FRIEDLANDER, L.; FAGIUOLI, S. et al. - Response to interferon a therapy is influenced by the iron content of the liver. J. Hepat., 20: 410-415, 1994.

[19] 19. YOSHIOKA, K.; KAKAMU, S.; AIYAMA, T. - Detection of serum antibodies to E2/NS1 hypervariable region of hepatitis C virus. Hepatology, 20: 231A, 1994.

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