Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon

E. Jenny L Heathcote, Stephen James, Kevin D. Mullen, S. C. Hauser, H. Rosenblate, Donald G. Albert, R. Bailey, V. G. Bain, K. Bala, L. A. Balart, H. Bonkovsky, M. Black, W. M. Cassidy, J. Donovan, M. Ehrinpreis, G. T. Everson, S. V. Feinman, R. T. Foust, H. Fromm, J. C. HoefsE. B. Hollinger, D. M. Jensen, P. G. Killenberg, E. B. Keeffe, E. L. Krawitt, S. Lee, W. M. Lee, D. J. VanLeeuwen, H. R. Lesesne, K. D. Lyche, J. McHutchison, G. Y. Minuk, K. M. Payne, N. R. Pimstone, P. J. Pockros, K. R. Reddy, D. A. Shafritz, C. I. Smith, M. J. Tong, B. E. Willems, J. Willis

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Abstract

Patients with chronic hepatitis C who have not had a sustained hepatitis C virus (HCV)-RNA response or serum alanine transaminase (ALT) response to a 6-month course of interferon (IFN) may respond to higher dose retreatment with consensus interferon (CIFN). Some nonresponders to initial IFN treatment have a transient response defined as undetectable HCV RNA or normalization of ALT during treatment, but subsequently have a 'breakthrough' while still on treatment. The aim of this study was to determine if nonresponders who had breakthroughs responded differently to CIFN retreatment than nonresponders without breakthroughs using data from a large, multicenter trial. ALT and HCV RNA were monitored frequently during initial IFN therapy (either 9 mcg CIFN or 3 MU IFN-α2b 3 times per week). HCV-RNA breakthroughs were observed in 86 of 467 (18%) of all treated patients, and ALT breakthroughs were observed in 90 of 467 (19%) of all treated patients. There was no association between breakthroughs and the presence of either binding or neutralizing anti-IFN antibodies. When the patients who were nonresponders to initial IFN treatment were retreated with CIFN (15 mcg) for 12 months, 27% of those with viral breakthroughs had a sustained viral response compared with 8% in prior nonresponders without breakthroughs (P =. 102). Sustained ALT responses were observed in 39% with breakthroughs compared with 10% in those without breakthroughs (P = .014). The data suggest that prior nonresponders with breakthroughs have a greater chance of responding to retreatment than do nonresponders without breakthroughs. However, most breakthrough patients would be missed unless repeated HCV-RNA testing were conducted during therapy.

Original languageEnglish (US)
Pages (from-to)562-566
Number of pages5
JournalHepatology
Volume30
Issue number2
DOIs
StatePublished - 1999

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Chronic Hepatitis C
Hepacivirus
Interferons
Alanine Transaminase
Retreatment
RNA
Therapeutics
Neutralizing Antibodies
Multicenter Studies
Anti-Idiotypic Antibodies

ASJC Scopus subject areas

  • Hepatology

Cite this

Heathcote, E. J. L., James, S., Mullen, K. D., Hauser, S. C., Rosenblate, H., Albert, D. G., ... Willis, J. (1999). Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon. Hepatology, 30(2), 562-566. https://doi.org/10.1002/hep.510300202

Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon. / Heathcote, E. Jenny L; James, Stephen; Mullen, Kevin D.; Hauser, S. C.; Rosenblate, H.; Albert, Donald G.; Bailey, R.; Bain, V. G.; Bala, K.; Balart, L. A.; Bonkovsky, H.; Black, M.; Cassidy, W. M.; Donovan, J.; Ehrinpreis, M.; Everson, G. T.; Feinman, S. V.; Foust, R. T.; Fromm, H.; Hoefs, J. C.; Hollinger, E. B.; Jensen, D. M.; Killenberg, P. G.; Keeffe, E. B.; Krawitt, E. L.; Lee, S.; Lee, W. M.; VanLeeuwen, D. J.; Lesesne, H. R.; Lyche, K. D.; McHutchison, J.; Minuk, G. Y.; Payne, K. M.; Pimstone, N. R.; Pockros, P. J.; Reddy, K. R.; Shafritz, D. A.; Smith, C. I.; Tong, M. J.; Willems, B. E.; Willis, J.

In: Hepatology, Vol. 30, No. 2, 1999, p. 562-566.

Research output: Contribution to journalArticle

Heathcote, EJL, James, S, Mullen, KD, Hauser, SC, Rosenblate, H, Albert, DG, Bailey, R, Bain, VG, Bala, K, Balart, LA, Bonkovsky, H, Black, M, Cassidy, WM, Donovan, J, Ehrinpreis, M, Everson, GT, Feinman, SV, Foust, RT, Fromm, H, Hoefs, JC, Hollinger, EB, Jensen, DM, Killenberg, PG, Keeffe, EB, Krawitt, EL, Lee, S, Lee, WM, VanLeeuwen, DJ, Lesesne, HR, Lyche, KD, McHutchison, J, Minuk, GY, Payne, KM, Pimstone, NR, Pockros, PJ, Reddy, KR, Shafritz, DA, Smith, CI, Tong, MJ, Willems, BE & Willis, J 1999, 'Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon', Hepatology, vol. 30, no. 2, pp. 562-566. https://doi.org/10.1002/hep.510300202
Heathcote, E. Jenny L ; James, Stephen ; Mullen, Kevin D. ; Hauser, S. C. ; Rosenblate, H. ; Albert, Donald G. ; Bailey, R. ; Bain, V. G. ; Bala, K. ; Balart, L. A. ; Bonkovsky, H. ; Black, M. ; Cassidy, W. M. ; Donovan, J. ; Ehrinpreis, M. ; Everson, G. T. ; Feinman, S. V. ; Foust, R. T. ; Fromm, H. ; Hoefs, J. C. ; Hollinger, E. B. ; Jensen, D. M. ; Killenberg, P. G. ; Keeffe, E. B. ; Krawitt, E. L. ; Lee, S. ; Lee, W. M. ; VanLeeuwen, D. J. ; Lesesne, H. R. ; Lyche, K. D. ; McHutchison, J. ; Minuk, G. Y. ; Payne, K. M. ; Pimstone, N. R. ; Pockros, P. J. ; Reddy, K. R. ; Shafritz, D. A. ; Smith, C. I. ; Tong, M. J. ; Willems, B. E. ; Willis, J. / Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon. In: Hepatology. 1999 ; Vol. 30, No. 2. pp. 562-566.
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title = "Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon",
abstract = "Patients with chronic hepatitis C who have not had a sustained hepatitis C virus (HCV)-RNA response or serum alanine transaminase (ALT) response to a 6-month course of interferon (IFN) may respond to higher dose retreatment with consensus interferon (CIFN). Some nonresponders to initial IFN treatment have a transient response defined as undetectable HCV RNA or normalization of ALT during treatment, but subsequently have a 'breakthrough' while still on treatment. The aim of this study was to determine if nonresponders who had breakthroughs responded differently to CIFN retreatment than nonresponders without breakthroughs using data from a large, multicenter trial. ALT and HCV RNA were monitored frequently during initial IFN therapy (either 9 mcg CIFN or 3 MU IFN-α2b 3 times per week). HCV-RNA breakthroughs were observed in 86 of 467 (18{\%}) of all treated patients, and ALT breakthroughs were observed in 90 of 467 (19{\%}) of all treated patients. There was no association between breakthroughs and the presence of either binding or neutralizing anti-IFN antibodies. When the patients who were nonresponders to initial IFN treatment were retreated with CIFN (15 mcg) for 12 months, 27{\%} of those with viral breakthroughs had a sustained viral response compared with 8{\%} in prior nonresponders without breakthroughs (P =. 102). Sustained ALT responses were observed in 39{\%} with breakthroughs compared with 10{\%} in those without breakthroughs (P = .014). The data suggest that prior nonresponders with breakthroughs have a greater chance of responding to retreatment than do nonresponders without breakthroughs. However, most breakthrough patients would be missed unless repeated HCV-RNA testing were conducted during therapy.",
author = "Heathcote, {E. Jenny L} and Stephen James and Mullen, {Kevin D.} and Hauser, {S. C.} and H. Rosenblate and Albert, {Donald G.} and R. Bailey and Bain, {V. G.} and K. Bala and Balart, {L. A.} and H. Bonkovsky and M. Black and Cassidy, {W. M.} and J. Donovan and M. Ehrinpreis and Everson, {G. T.} and Feinman, {S. V.} and Foust, {R. T.} and H. Fromm and Hoefs, {J. C.} and Hollinger, {E. B.} and Jensen, {D. M.} and Killenberg, {P. G.} and Keeffe, {E. B.} and Krawitt, {E. L.} and S. Lee and Lee, {W. M.} and VanLeeuwen, {D. J.} and Lesesne, {H. R.} and Lyche, {K. D.} and J. McHutchison and Minuk, {G. Y.} and Payne, {K. M.} and Pimstone, {N. R.} and Pockros, {P. J.} and Reddy, {K. R.} and Shafritz, {D. A.} and Smith, {C. I.} and Tong, {M. J.} and Willems, {B. E.} and J. Willis",
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T1 - Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon

AU - Heathcote, E. Jenny L

AU - James, Stephen

AU - Mullen, Kevin D.

AU - Hauser, S. C.

AU - Rosenblate, H.

AU - Albert, Donald G.

AU - Bailey, R.

AU - Bain, V. G.

AU - Bala, K.

AU - Balart, L. A.

AU - Bonkovsky, H.

AU - Black, M.

AU - Cassidy, W. M.

AU - Donovan, J.

AU - Ehrinpreis, M.

AU - Everson, G. T.

AU - Feinman, S. V.

AU - Foust, R. T.

AU - Fromm, H.

AU - Hoefs, J. C.

AU - Hollinger, E. B.

AU - Jensen, D. M.

AU - Killenberg, P. G.

AU - Keeffe, E. B.

AU - Krawitt, E. L.

AU - Lee, S.

AU - Lee, W. M.

AU - VanLeeuwen, D. J.

AU - Lesesne, H. R.

AU - Lyche, K. D.

AU - McHutchison, J.

AU - Minuk, G. Y.

AU - Payne, K. M.

AU - Pimstone, N. R.

AU - Pockros, P. J.

AU - Reddy, K. R.

AU - Shafritz, D. A.

AU - Smith, C. I.

AU - Tong, M. J.

AU - Willems, B. E.

AU - Willis, J.

PY - 1999

Y1 - 1999

N2 - Patients with chronic hepatitis C who have not had a sustained hepatitis C virus (HCV)-RNA response or serum alanine transaminase (ALT) response to a 6-month course of interferon (IFN) may respond to higher dose retreatment with consensus interferon (CIFN). Some nonresponders to initial IFN treatment have a transient response defined as undetectable HCV RNA or normalization of ALT during treatment, but subsequently have a 'breakthrough' while still on treatment. The aim of this study was to determine if nonresponders who had breakthroughs responded differently to CIFN retreatment than nonresponders without breakthroughs using data from a large, multicenter trial. ALT and HCV RNA were monitored frequently during initial IFN therapy (either 9 mcg CIFN or 3 MU IFN-α2b 3 times per week). HCV-RNA breakthroughs were observed in 86 of 467 (18%) of all treated patients, and ALT breakthroughs were observed in 90 of 467 (19%) of all treated patients. There was no association between breakthroughs and the presence of either binding or neutralizing anti-IFN antibodies. When the patients who were nonresponders to initial IFN treatment were retreated with CIFN (15 mcg) for 12 months, 27% of those with viral breakthroughs had a sustained viral response compared with 8% in prior nonresponders without breakthroughs (P =. 102). Sustained ALT responses were observed in 39% with breakthroughs compared with 10% in those without breakthroughs (P = .014). The data suggest that prior nonresponders with breakthroughs have a greater chance of responding to retreatment than do nonresponders without breakthroughs. However, most breakthrough patients would be missed unless repeated HCV-RNA testing were conducted during therapy.

AB - Patients with chronic hepatitis C who have not had a sustained hepatitis C virus (HCV)-RNA response or serum alanine transaminase (ALT) response to a 6-month course of interferon (IFN) may respond to higher dose retreatment with consensus interferon (CIFN). Some nonresponders to initial IFN treatment have a transient response defined as undetectable HCV RNA or normalization of ALT during treatment, but subsequently have a 'breakthrough' while still on treatment. The aim of this study was to determine if nonresponders who had breakthroughs responded differently to CIFN retreatment than nonresponders without breakthroughs using data from a large, multicenter trial. ALT and HCV RNA were monitored frequently during initial IFN therapy (either 9 mcg CIFN or 3 MU IFN-α2b 3 times per week). HCV-RNA breakthroughs were observed in 86 of 467 (18%) of all treated patients, and ALT breakthroughs were observed in 90 of 467 (19%) of all treated patients. There was no association between breakthroughs and the presence of either binding or neutralizing anti-IFN antibodies. When the patients who were nonresponders to initial IFN treatment were retreated with CIFN (15 mcg) for 12 months, 27% of those with viral breakthroughs had a sustained viral response compared with 8% in prior nonresponders without breakthroughs (P =. 102). Sustained ALT responses were observed in 39% with breakthroughs compared with 10% in those without breakthroughs (P = .014). The data suggest that prior nonresponders with breakthroughs have a greater chance of responding to retreatment than do nonresponders without breakthroughs. However, most breakthrough patients would be missed unless repeated HCV-RNA testing were conducted during therapy.

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