Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon

Adrian M. Di Bisceglie, Mitchell L. Shiffman, Gregory T. Everson, Karen L. Lindsay, James E. Everhart, Elizabeth C. Wright, William M. Lee, Anna S. Lok, Herbert L. Bonkovsky, Timothy R. Morgan, Marc G. Ghany, Chihiro Morishima, Kristin K. Snow, Jules L. Dienstag

Research output: Contribution to journalArticle

375 Citations (Scopus)

Abstract

Background: In patients with chronic hepatitis C who do not have a response to antiviral treatment, the disease may progress to cirrhosis, liver failure, hepatocellular carcinoma, and death. Whether long-term antiviral therapy can prevent progressive liver disease in such patients remains uncertain. Methods: We conducted a randomized, controlled trial of peginterferon alfa-2a at a dosage of 90 ?g per week for 3.5 years, as compared with no treatment, in 1050 patients with chronic hepatitis C and advanced fibrosis who had not had a response to previous therapy with peginterferon and ribavirin. The patients, who were stratified according to stage of fibrosis (622 with noncirrhotic fibrosis and 428 with cirrhosis), were seen at 3-month intervals and underwent liver biopsy at 1.5 and 3.5 years after randomization. The primary end point was progression of liver disease, as indicated by death, hepatocellular carcinoma, hepatic decompensation, or, for those with bridging fibrosis at baseline, an increase in the Ishak fibrosis score of 2 or more points. Results: We randomly assigned the patients to receive peginterferon (517 patients) or no therapy (533 patients) for 3.5 years. The level of serum aminotransferases, the level of serum hepatitis C virus RNA, and histologic necroinflammatory scores all decreased significantly (P<0.001) with treatment, but there was no significant difference between the groups in the rate of any primary outcome (34.1% in the treatment group and 33.8% in the control group; hazard ratio, 1.01; 95% confidence interval, 0.81 to 1.27; P = 0.90). The percentage of patients with at least one serious adverse event was 38.6% in the treatment group and 31.8% in the control group (P = 0.07). Conclusions: Long-term therapy with peginterferon did not reduce the rate of disease progression in patients with chronic hepatitis C and advanced fibrosis, with or without cirrhosis, who had not had a response to initial treatment with peginterferon and ribavirin. (ClinicalTrials.gov number, NCT00006164.).

Original languageEnglish (US)
Pages (from-to)2429-2441
Number of pages13
JournalNew England Journal of Medicine
Volume359
Issue number23
DOIs
StatePublished - Dec 4 2008

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Chronic Hepatitis C
Fibrosis
Therapeutics
Ribavirin
Antiviral Agents
Liver Diseases
Hepatocellular Carcinoma
Control Groups
Liver
Liver Failure
Random Allocation
Transaminases
Serum
Hepacivirus
Disease Progression
Randomized Controlled Trials
RNA
Confidence Intervals
Biopsy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Di Bisceglie, A. M., Shiffman, M. L., Everson, G. T., Lindsay, K. L., Everhart, J. E., Wright, E. C., ... Dienstag, J. L. (2008). Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. New England Journal of Medicine, 359(23), 2429-2441. https://doi.org/10.1056/NEJMoa0707615

Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. / Di Bisceglie, Adrian M.; Shiffman, Mitchell L.; Everson, Gregory T.; Lindsay, Karen L.; Everhart, James E.; Wright, Elizabeth C.; Lee, William M.; Lok, Anna S.; Bonkovsky, Herbert L.; Morgan, Timothy R.; Ghany, Marc G.; Morishima, Chihiro; Snow, Kristin K.; Dienstag, Jules L.

In: New England Journal of Medicine, Vol. 359, No. 23, 04.12.2008, p. 2429-2441.

Research output: Contribution to journalArticle

Di Bisceglie, AM, Shiffman, ML, Everson, GT, Lindsay, KL, Everhart, JE, Wright, EC, Lee, WM, Lok, AS, Bonkovsky, HL, Morgan, TR, Ghany, MG, Morishima, C, Snow, KK & Dienstag, JL 2008, 'Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon', New England Journal of Medicine, vol. 359, no. 23, pp. 2429-2441. https://doi.org/10.1056/NEJMoa0707615
Di Bisceglie AM, Shiffman ML, Everson GT, Lindsay KL, Everhart JE, Wright EC et al. Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. New England Journal of Medicine. 2008 Dec 4;359(23):2429-2441. https://doi.org/10.1056/NEJMoa0707615
Di Bisceglie, Adrian M. ; Shiffman, Mitchell L. ; Everson, Gregory T. ; Lindsay, Karen L. ; Everhart, James E. ; Wright, Elizabeth C. ; Lee, William M. ; Lok, Anna S. ; Bonkovsky, Herbert L. ; Morgan, Timothy R. ; Ghany, Marc G. ; Morishima, Chihiro ; Snow, Kristin K. ; Dienstag, Jules L. / Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. In: New England Journal of Medicine. 2008 ; Vol. 359, No. 23. pp. 2429-2441.
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abstract = "Background: In patients with chronic hepatitis C who do not have a response to antiviral treatment, the disease may progress to cirrhosis, liver failure, hepatocellular carcinoma, and death. Whether long-term antiviral therapy can prevent progressive liver disease in such patients remains uncertain. Methods: We conducted a randomized, controlled trial of peginterferon alfa-2a at a dosage of 90 ?g per week for 3.5 years, as compared with no treatment, in 1050 patients with chronic hepatitis C and advanced fibrosis who had not had a response to previous therapy with peginterferon and ribavirin. The patients, who were stratified according to stage of fibrosis (622 with noncirrhotic fibrosis and 428 with cirrhosis), were seen at 3-month intervals and underwent liver biopsy at 1.5 and 3.5 years after randomization. The primary end point was progression of liver disease, as indicated by death, hepatocellular carcinoma, hepatic decompensation, or, for those with bridging fibrosis at baseline, an increase in the Ishak fibrosis score of 2 or more points. Results: We randomly assigned the patients to receive peginterferon (517 patients) or no therapy (533 patients) for 3.5 years. The level of serum aminotransferases, the level of serum hepatitis C virus RNA, and histologic necroinflammatory scores all decreased significantly (P<0.001) with treatment, but there was no significant difference between the groups in the rate of any primary outcome (34.1{\%} in the treatment group and 33.8{\%} in the control group; hazard ratio, 1.01; 95{\%} confidence interval, 0.81 to 1.27; P = 0.90). The percentage of patients with at least one serious adverse event was 38.6{\%} in the treatment group and 31.8{\%} in the control group (P = 0.07). Conclusions: Long-term therapy with peginterferon did not reduce the rate of disease progression in patients with chronic hepatitis C and advanced fibrosis, with or without cirrhosis, who had not had a response to initial treatment with peginterferon and ribavirin. (ClinicalTrials.gov number, NCT00006164.).",
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AU - Di Bisceglie, Adrian M.

AU - Shiffman, Mitchell L.

AU - Everson, Gregory T.

AU - Lindsay, Karen L.

AU - Everhart, James E.

AU - Wright, Elizabeth C.

AU - Lee, William M.

AU - Lok, Anna S.

AU - Bonkovsky, Herbert L.

AU - Morgan, Timothy R.

AU - Ghany, Marc G.

AU - Morishima, Chihiro

AU - Snow, Kristin K.

AU - Dienstag, Jules L.

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N2 - Background: In patients with chronic hepatitis C who do not have a response to antiviral treatment, the disease may progress to cirrhosis, liver failure, hepatocellular carcinoma, and death. Whether long-term antiviral therapy can prevent progressive liver disease in such patients remains uncertain. Methods: We conducted a randomized, controlled trial of peginterferon alfa-2a at a dosage of 90 ?g per week for 3.5 years, as compared with no treatment, in 1050 patients with chronic hepatitis C and advanced fibrosis who had not had a response to previous therapy with peginterferon and ribavirin. The patients, who were stratified according to stage of fibrosis (622 with noncirrhotic fibrosis and 428 with cirrhosis), were seen at 3-month intervals and underwent liver biopsy at 1.5 and 3.5 years after randomization. The primary end point was progression of liver disease, as indicated by death, hepatocellular carcinoma, hepatic decompensation, or, for those with bridging fibrosis at baseline, an increase in the Ishak fibrosis score of 2 or more points. Results: We randomly assigned the patients to receive peginterferon (517 patients) or no therapy (533 patients) for 3.5 years. The level of serum aminotransferases, the level of serum hepatitis C virus RNA, and histologic necroinflammatory scores all decreased significantly (P<0.001) with treatment, but there was no significant difference between the groups in the rate of any primary outcome (34.1% in the treatment group and 33.8% in the control group; hazard ratio, 1.01; 95% confidence interval, 0.81 to 1.27; P = 0.90). The percentage of patients with at least one serious adverse event was 38.6% in the treatment group and 31.8% in the control group (P = 0.07). Conclusions: Long-term therapy with peginterferon did not reduce the rate of disease progression in patients with chronic hepatitis C and advanced fibrosis, with or without cirrhosis, who had not had a response to initial treatment with peginterferon and ribavirin. (ClinicalTrials.gov number, NCT00006164.).

AB - Background: In patients with chronic hepatitis C who do not have a response to antiviral treatment, the disease may progress to cirrhosis, liver failure, hepatocellular carcinoma, and death. Whether long-term antiviral therapy can prevent progressive liver disease in such patients remains uncertain. Methods: We conducted a randomized, controlled trial of peginterferon alfa-2a at a dosage of 90 ?g per week for 3.5 years, as compared with no treatment, in 1050 patients with chronic hepatitis C and advanced fibrosis who had not had a response to previous therapy with peginterferon and ribavirin. The patients, who were stratified according to stage of fibrosis (622 with noncirrhotic fibrosis and 428 with cirrhosis), were seen at 3-month intervals and underwent liver biopsy at 1.5 and 3.5 years after randomization. The primary end point was progression of liver disease, as indicated by death, hepatocellular carcinoma, hepatic decompensation, or, for those with bridging fibrosis at baseline, an increase in the Ishak fibrosis score of 2 or more points. Results: We randomly assigned the patients to receive peginterferon (517 patients) or no therapy (533 patients) for 3.5 years. The level of serum aminotransferases, the level of serum hepatitis C virus RNA, and histologic necroinflammatory scores all decreased significantly (P<0.001) with treatment, but there was no significant difference between the groups in the rate of any primary outcome (34.1% in the treatment group and 33.8% in the control group; hazard ratio, 1.01; 95% confidence interval, 0.81 to 1.27; P = 0.90). The percentage of patients with at least one serious adverse event was 38.6% in the treatment group and 31.8% in the control group (P = 0.07). Conclusions: Long-term therapy with peginterferon did not reduce the rate of disease progression in patients with chronic hepatitis C and advanced fibrosis, with or without cirrhosis, who had not had a response to initial treatment with peginterferon and ribavirin. (ClinicalTrials.gov number, NCT00006164.).

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