A randomized, controlled trial of interferon ALFA-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B

Robert P. Perrillo, Eugene R Schiff, Gary L. Davis, Henry C. Bodenheimer, Karen Lindsay, John Payne, Jules L. Dienstag, Christopher B O'Brien, Carlo Tamburro, Ira M. Jacobson, Richard Sampliner, David Feit, Jay Lefkowitch, Mary Kuhns, Carlton Meschievitz, Bharati Sanghvi, Janice Albrecht, Alexandra Gibas, Robert P. Perrillo, Fredric G. RegensteinKenneth Schechtman, Carol J. Bodicky, Eugene R. Schiff, Steven Villanueva, Gary L. Davis, Joanne Kniffen, Henry C. Bodenheimer, Carmel A. Brodeur, Karen L. Lindsay, Susan Milstein, Klaus Lewin, John Payne, Mary Jo Mikotis, Jules L. Dienstag, Alexandra Gibas, Heather Cody, Eloise Watkins, Christopher O'Brien, Michelle Sample, Carlo H. Tamburro, Barbara Miller, Richard Sampliner, Cindy Mackel, Ira M. Jacobson, Michael Cantor, David Feit, Jay Lefkowitch, Mary C. Kuhns, Anne L. McNamara, Ann Kilian, Steve Bariletto, Kenneth Guito, Janice Albrecht, Carlton Meschievitz, Robert B. Kammer, Bharati Sanghvi

Research output: Contribution to journalArticle

743 Citations (Scopus)

Abstract

Background and Methods. Chronic hepatitis B is a common and often progressive liver disorder for which there is no accepted therapy. To assess the efficacy of treatment with interferon, we randomly assigned patients with chronic hepatitis B to one of the following regimens: prednisone for 6 weeks followed by 5 million units of recombinant interferon alfa-2b daily for 16 weeks; placebo followed by 5 million units of interferon daily for 16 weeks; placebo followed by 1 million units of interferon daily for 16 weeks; or observation with no treatment. Results. Hepatitis B e antigen and hepatitis B viral DNA disappeared from serum significantly more often in the patients given prednisone plus interferon (16 of 44 patients, or 36 percent) or 5 million units of interferon alone (15 of 41; 37 percent) than in the untreated controls (3 of 43; 7 percent; P<0.001); the difference between those given 1 million units of interferon (7 of 41; 17 percent) and the controls was not significant. The strongest independent predictor of a response to treatment was the amount of hepatitis B viral DNA in serum at entry (P<0.0001). Of the 38 patients who responded to interferon, 33 (87 percent) had normal serum aminotransferase levels after therapy; 11 patients who responded (29 percent), but no controls, lost the hepatitis B surface antigen. Blinded histologic assessment revealed a significant improvement in periportal necrosis in the treated patients (P = 0.03). Conclusions. In chronic hepatitis B, treatment with interferon alfa-2b (5 million units per day for 16 weeks) was effective in inducing a sustained loss of viral replication and achieving remission, assessed biochemically and histologically, in over a third of patients. Moreover, in about 10 percent of the patients treated with interferon, hepatitis B surface antigen disappeared from serum.

Original languageEnglish
Pages (from-to)295-301
Number of pages7
JournalNew England Journal of Medicine
Volume323
Issue number5
StatePublished - Aug 2 1990

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Chronic Hepatitis B
Prednisone
Interferons
Randomized Controlled Trials
interferon alfa-2b
Viral DNA
Therapeutics
Hepatitis B Surface Antigens
Hepatitis B
Serum
Placebos
Hepatitis B e Antigens
Transaminases
Interferon-alpha
Necrosis
Observation
Liver

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Perrillo, R. P., Schiff, E. R., Davis, G. L., Bodenheimer, H. C., Lindsay, K., Payne, J., ... Sanghvi, B. (1990). A randomized, controlled trial of interferon ALFA-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. New England Journal of Medicine, 323(5), 295-301.

A randomized, controlled trial of interferon ALFA-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. / Perrillo, Robert P.; Schiff, Eugene R; Davis, Gary L.; Bodenheimer, Henry C.; Lindsay, Karen; Payne, John; Dienstag, Jules L.; O'Brien, Christopher B; Tamburro, Carlo; Jacobson, Ira M.; Sampliner, Richard; Feit, David; Lefkowitch, Jay; Kuhns, Mary; Meschievitz, Carlton; Sanghvi, Bharati; Albrecht, Janice; Gibas, Alexandra; Perrillo, Robert P.; Regenstein, Fredric G.; Schechtman, Kenneth; Bodicky, Carol J.; Schiff, Eugene R.; Villanueva, Steven; Davis, Gary L.; Kniffen, Joanne; Bodenheimer, Henry C.; Brodeur, Carmel A.; Lindsay, Karen L.; Milstein, Susan; Lewin, Klaus; Payne, John; Mikotis, Mary Jo; Dienstag, Jules L.; Gibas, Alexandra; Cody, Heather; Watkins, Eloise; O'Brien, Christopher; Sample, Michelle; Tamburro, Carlo H.; Miller, Barbara; Sampliner, Richard; Mackel, Cindy; Jacobson, Ira M.; Cantor, Michael; Feit, David; Lefkowitch, Jay; Kuhns, Mary C.; McNamara, Anne L.; Kilian, Ann; Bariletto, Steve; Guito, Kenneth; Albrecht, Janice; Meschievitz, Carlton; Kammer, Robert B.; Sanghvi, Bharati.

In: New England Journal of Medicine, Vol. 323, No. 5, 02.08.1990, p. 295-301.

Research output: Contribution to journalArticle

Perrillo, RP, Schiff, ER, Davis, GL, Bodenheimer, HC, Lindsay, K, Payne, J, Dienstag, JL, O'Brien, CB, Tamburro, C, Jacobson, IM, Sampliner, R, Feit, D, Lefkowitch, J, Kuhns, M, Meschievitz, C, Sanghvi, B, Albrecht, J, Gibas, A, Perrillo, RP, Regenstein, FG, Schechtman, K, Bodicky, CJ, Schiff, ER, Villanueva, S, Davis, GL, Kniffen, J, Bodenheimer, HC, Brodeur, CA, Lindsay, KL, Milstein, S, Lewin, K, Payne, J, Mikotis, MJ, Dienstag, JL, Gibas, A, Cody, H, Watkins, E, O'Brien, C, Sample, M, Tamburro, CH, Miller, B, Sampliner, R, Mackel, C, Jacobson, IM, Cantor, M, Feit, D, Lefkowitch, J, Kuhns, MC, McNamara, AL, Kilian, A, Bariletto, S, Guito, K, Albrecht, J, Meschievitz, C, Kammer, RB & Sanghvi, B 1990, 'A randomized, controlled trial of interferon ALFA-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B', New England Journal of Medicine, vol. 323, no. 5, pp. 295-301.
Perrillo, Robert P. ; Schiff, Eugene R ; Davis, Gary L. ; Bodenheimer, Henry C. ; Lindsay, Karen ; Payne, John ; Dienstag, Jules L. ; O'Brien, Christopher B ; Tamburro, Carlo ; Jacobson, Ira M. ; Sampliner, Richard ; Feit, David ; Lefkowitch, Jay ; Kuhns, Mary ; Meschievitz, Carlton ; Sanghvi, Bharati ; Albrecht, Janice ; Gibas, Alexandra ; Perrillo, Robert P. ; Regenstein, Fredric G. ; Schechtman, Kenneth ; Bodicky, Carol J. ; Schiff, Eugene R. ; Villanueva, Steven ; Davis, Gary L. ; Kniffen, Joanne ; Bodenheimer, Henry C. ; Brodeur, Carmel A. ; Lindsay, Karen L. ; Milstein, Susan ; Lewin, Klaus ; Payne, John ; Mikotis, Mary Jo ; Dienstag, Jules L. ; Gibas, Alexandra ; Cody, Heather ; Watkins, Eloise ; O'Brien, Christopher ; Sample, Michelle ; Tamburro, Carlo H. ; Miller, Barbara ; Sampliner, Richard ; Mackel, Cindy ; Jacobson, Ira M. ; Cantor, Michael ; Feit, David ; Lefkowitch, Jay ; Kuhns, Mary C. ; McNamara, Anne L. ; Kilian, Ann ; Bariletto, Steve ; Guito, Kenneth ; Albrecht, Janice ; Meschievitz, Carlton ; Kammer, Robert B. ; Sanghvi, Bharati. / A randomized, controlled trial of interferon ALFA-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. In: New England Journal of Medicine. 1990 ; Vol. 323, No. 5. pp. 295-301.
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abstract = "Background and Methods. Chronic hepatitis B is a common and often progressive liver disorder for which there is no accepted therapy. To assess the efficacy of treatment with interferon, we randomly assigned patients with chronic hepatitis B to one of the following regimens: prednisone for 6 weeks followed by 5 million units of recombinant interferon alfa-2b daily for 16 weeks; placebo followed by 5 million units of interferon daily for 16 weeks; placebo followed by 1 million units of interferon daily for 16 weeks; or observation with no treatment. Results. Hepatitis B e antigen and hepatitis B viral DNA disappeared from serum significantly more often in the patients given prednisone plus interferon (16 of 44 patients, or 36 percent) or 5 million units of interferon alone (15 of 41; 37 percent) than in the untreated controls (3 of 43; 7 percent; P<0.001); the difference between those given 1 million units of interferon (7 of 41; 17 percent) and the controls was not significant. The strongest independent predictor of a response to treatment was the amount of hepatitis B viral DNA in serum at entry (P<0.0001). Of the 38 patients who responded to interferon, 33 (87 percent) had normal serum aminotransferase levels after therapy; 11 patients who responded (29 percent), but no controls, lost the hepatitis B surface antigen. Blinded histologic assessment revealed a significant improvement in periportal necrosis in the treated patients (P = 0.03). Conclusions. In chronic hepatitis B, treatment with interferon alfa-2b (5 million units per day for 16 weeks) was effective in inducing a sustained loss of viral replication and achieving remission, assessed biochemically and histologically, in over a third of patients. Moreover, in about 10 percent of the patients treated with interferon, hepatitis B surface antigen disappeared from serum.",
author = "Perrillo, {Robert P.} and Schiff, {Eugene R} and Davis, {Gary L.} and Bodenheimer, {Henry C.} and Karen Lindsay and John Payne and Dienstag, {Jules L.} and O'Brien, {Christopher B} and Carlo Tamburro and Jacobson, {Ira M.} and Richard Sampliner and David Feit and Jay Lefkowitch and Mary Kuhns and Carlton Meschievitz and Bharati Sanghvi and Janice Albrecht and Alexandra Gibas and Perrillo, {Robert P.} and Regenstein, {Fredric G.} and Kenneth Schechtman and Bodicky, {Carol J.} and Schiff, {Eugene R.} and Steven Villanueva and Davis, {Gary L.} and Joanne Kniffen and Bodenheimer, {Henry C.} and Brodeur, {Carmel A.} and Lindsay, {Karen L.} and Susan Milstein and Klaus Lewin and John Payne and Mikotis, {Mary Jo} and Dienstag, {Jules L.} and Alexandra Gibas and Heather Cody and Eloise Watkins and Christopher O'Brien and Michelle Sample and Tamburro, {Carlo H.} and Barbara Miller and Richard Sampliner and Cindy Mackel and Jacobson, {Ira M.} and Michael Cantor and David Feit and Jay Lefkowitch and Kuhns, {Mary C.} and McNamara, {Anne L.} and Ann Kilian and Steve Bariletto and Kenneth Guito and Janice Albrecht and Carlton Meschievitz and Kammer, {Robert B.} and Bharati Sanghvi",
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T1 - A randomized, controlled trial of interferon ALFA-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B

AU - Perrillo, Robert P.

AU - Schiff, Eugene R

AU - Davis, Gary L.

AU - Bodenheimer, Henry C.

AU - Lindsay, Karen

AU - Payne, John

AU - Dienstag, Jules L.

AU - O'Brien, Christopher B

AU - Tamburro, Carlo

AU - Jacobson, Ira M.

AU - Sampliner, Richard

AU - Feit, David

AU - Lefkowitch, Jay

AU - Kuhns, Mary

AU - Meschievitz, Carlton

AU - Sanghvi, Bharati

AU - Albrecht, Janice

AU - Gibas, Alexandra

AU - Perrillo, Robert P.

AU - Regenstein, Fredric G.

AU - Schechtman, Kenneth

AU - Bodicky, Carol J.

AU - Schiff, Eugene R.

AU - Villanueva, Steven

AU - Davis, Gary L.

AU - Kniffen, Joanne

AU - Bodenheimer, Henry C.

AU - Brodeur, Carmel A.

AU - Lindsay, Karen L.

AU - Milstein, Susan

AU - Lewin, Klaus

AU - Payne, John

AU - Mikotis, Mary Jo

AU - Dienstag, Jules L.

AU - Gibas, Alexandra

AU - Cody, Heather

AU - Watkins, Eloise

AU - O'Brien, Christopher

AU - Sample, Michelle

AU - Tamburro, Carlo H.

AU - Miller, Barbara

AU - Sampliner, Richard

AU - Mackel, Cindy

AU - Jacobson, Ira M.

AU - Cantor, Michael

AU - Feit, David

AU - Lefkowitch, Jay

AU - Kuhns, Mary C.

AU - McNamara, Anne L.

AU - Kilian, Ann

AU - Bariletto, Steve

AU - Guito, Kenneth

AU - Albrecht, Janice

AU - Meschievitz, Carlton

AU - Kammer, Robert B.

AU - Sanghvi, Bharati

PY - 1990/8/2

Y1 - 1990/8/2

N2 - Background and Methods. Chronic hepatitis B is a common and often progressive liver disorder for which there is no accepted therapy. To assess the efficacy of treatment with interferon, we randomly assigned patients with chronic hepatitis B to one of the following regimens: prednisone for 6 weeks followed by 5 million units of recombinant interferon alfa-2b daily for 16 weeks; placebo followed by 5 million units of interferon daily for 16 weeks; placebo followed by 1 million units of interferon daily for 16 weeks; or observation with no treatment. Results. Hepatitis B e antigen and hepatitis B viral DNA disappeared from serum significantly more often in the patients given prednisone plus interferon (16 of 44 patients, or 36 percent) or 5 million units of interferon alone (15 of 41; 37 percent) than in the untreated controls (3 of 43; 7 percent; P<0.001); the difference between those given 1 million units of interferon (7 of 41; 17 percent) and the controls was not significant. The strongest independent predictor of a response to treatment was the amount of hepatitis B viral DNA in serum at entry (P<0.0001). Of the 38 patients who responded to interferon, 33 (87 percent) had normal serum aminotransferase levels after therapy; 11 patients who responded (29 percent), but no controls, lost the hepatitis B surface antigen. Blinded histologic assessment revealed a significant improvement in periportal necrosis in the treated patients (P = 0.03). Conclusions. In chronic hepatitis B, treatment with interferon alfa-2b (5 million units per day for 16 weeks) was effective in inducing a sustained loss of viral replication and achieving remission, assessed biochemically and histologically, in over a third of patients. Moreover, in about 10 percent of the patients treated with interferon, hepatitis B surface antigen disappeared from serum.

AB - Background and Methods. Chronic hepatitis B is a common and often progressive liver disorder for which there is no accepted therapy. To assess the efficacy of treatment with interferon, we randomly assigned patients with chronic hepatitis B to one of the following regimens: prednisone for 6 weeks followed by 5 million units of recombinant interferon alfa-2b daily for 16 weeks; placebo followed by 5 million units of interferon daily for 16 weeks; placebo followed by 1 million units of interferon daily for 16 weeks; or observation with no treatment. Results. Hepatitis B e antigen and hepatitis B viral DNA disappeared from serum significantly more often in the patients given prednisone plus interferon (16 of 44 patients, or 36 percent) or 5 million units of interferon alone (15 of 41; 37 percent) than in the untreated controls (3 of 43; 7 percent; P<0.001); the difference between those given 1 million units of interferon (7 of 41; 17 percent) and the controls was not significant. The strongest independent predictor of a response to treatment was the amount of hepatitis B viral DNA in serum at entry (P<0.0001). Of the 38 patients who responded to interferon, 33 (87 percent) had normal serum aminotransferase levels after therapy; 11 patients who responded (29 percent), but no controls, lost the hepatitis B surface antigen. Blinded histologic assessment revealed a significant improvement in periportal necrosis in the treated patients (P = 0.03). Conclusions. In chronic hepatitis B, treatment with interferon alfa-2b (5 million units per day for 16 weeks) was effective in inducing a sustained loss of viral replication and achieving remission, assessed biochemically and histologically, in over a third of patients. Moreover, in about 10 percent of the patients treated with interferon, hepatitis B surface antigen disappeared from serum.

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