Effect of HCV RNA Suppression During Peginterferon Alfa-2a Maintenance Therapy on Clinical Outcomes in the HALT-C Trial

Mitchell L. Shiffman, Chihiro Morishima, Jules L. Dienstag, Karen L. Lindsay, John C. Hoefs, William M. Lee, Elizabeth C. Wright, Deepa Naishadham, Gregory T. Everson, Anna S. Lok, Adrian M. Di Bisceglie, Herbert L. Bonkovsky, Marc G. Ghany

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Abstract

Background & Aims: The Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial demonstrated that low-dose peginterferon maintenance therapy was ineffective in preventing clinical outcomes in patients with chronic hepatitis C, advanced fibrosis, and failure to achieve a sustained virologic response during lead-in phase treatment with standard dose peginterferon/ribavirin. This analysis was performed to determine whether suppressing HCV RNA during the trial was associated with a reduction in clinical outcomes. Methods: Seven hundred sixty-four patients treated during the lead-in phase of HALT-C trial were randomized to either peginterferon alfa-2a (90 μg/week) maintenance therapy or no treatment (control) for 3.5 years. Clinical outcomes included an increase in Child-Turcotte-Pugh score, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage, hepatocellular carcinoma, and mortality. Results: During the lead-in, ≥4-log10 decline in serum HCV RNA occurred in 178 patients; 82% of whom lost detectable HCV RNA and later broke through or relapsed. These patients had significantly (P = .003) fewer clinical outcomes whether randomized to maintenance therapy or control. Following randomization, serum HCV RNA increased significantly in all 90 control patients and in 58 of 88 receiving maintenance therapy. Only 30 patients had persistent suppression of HCV RNA by ≥4 log10 during maintenance therapy. No significant reduction in clinical outcomes was observed in these patients. Conclusions: Viral suppression by ≥4 log10 with full-dose peginterferon/ribavirin is associated with a significant reduction in clinical outcomes. Continuing low-dose peginterferon maintenance therapy, even in patients with persistent viral suppression, does not lead to a further decline in clinical outcomes.

Original languageEnglish (US)
Pages (from-to)1986-1994
Number of pages9
JournalGastroenterology
Volume137
Issue number6
DOIs
StatePublished - Dec 2009

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Hepatitis C
Antiviral Agents
Fibrosis
RNA
Therapeutics
Ribavirin
peginterferon alfa-2a
Hepatic Encephalopathy
Chronic Hepatitis C
Random Allocation
Peritonitis
Serum
Ascites
Hepatocellular Carcinoma
Hemorrhage
Mortality

ASJC Scopus subject areas

  • Gastroenterology

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Effect of HCV RNA Suppression During Peginterferon Alfa-2a Maintenance Therapy on Clinical Outcomes in the HALT-C Trial. / Shiffman, Mitchell L.; Morishima, Chihiro; Dienstag, Jules L.; Lindsay, Karen L.; Hoefs, John C.; Lee, William M.; Wright, Elizabeth C.; Naishadham, Deepa; Everson, Gregory T.; Lok, Anna S.; Di Bisceglie, Adrian M.; Bonkovsky, Herbert L.; Ghany, Marc G.

In: Gastroenterology, Vol. 137, No. 6, 12.2009, p. 1986-1994.

Research output: Contribution to journalArticle

Shiffman, ML, Morishima, C, Dienstag, JL, Lindsay, KL, Hoefs, JC, Lee, WM, Wright, EC, Naishadham, D, Everson, GT, Lok, AS, Di Bisceglie, AM, Bonkovsky, HL & Ghany, MG 2009, 'Effect of HCV RNA Suppression During Peginterferon Alfa-2a Maintenance Therapy on Clinical Outcomes in the HALT-C Trial', Gastroenterology, vol. 137, no. 6, pp. 1986-1994. https://doi.org/10.1053/j.gastro.2009.08.067
Shiffman, Mitchell L. ; Morishima, Chihiro ; Dienstag, Jules L. ; Lindsay, Karen L. ; Hoefs, John C. ; Lee, William M. ; Wright, Elizabeth C. ; Naishadham, Deepa ; Everson, Gregory T. ; Lok, Anna S. ; Di Bisceglie, Adrian M. ; Bonkovsky, Herbert L. ; Ghany, Marc G. / Effect of HCV RNA Suppression During Peginterferon Alfa-2a Maintenance Therapy on Clinical Outcomes in the HALT-C Trial. In: Gastroenterology. 2009 ; Vol. 137, No. 6. pp. 1986-1994.
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abstract = "Background & Aims: The Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial demonstrated that low-dose peginterferon maintenance therapy was ineffective in preventing clinical outcomes in patients with chronic hepatitis C, advanced fibrosis, and failure to achieve a sustained virologic response during lead-in phase treatment with standard dose peginterferon/ribavirin. This analysis was performed to determine whether suppressing HCV RNA during the trial was associated with a reduction in clinical outcomes. Methods: Seven hundred sixty-four patients treated during the lead-in phase of HALT-C trial were randomized to either peginterferon alfa-2a (90 μg/week) maintenance therapy or no treatment (control) for 3.5 years. Clinical outcomes included an increase in Child-Turcotte-Pugh score, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage, hepatocellular carcinoma, and mortality. Results: During the lead-in, ≥4-log10 decline in serum HCV RNA occurred in 178 patients; 82{\%} of whom lost detectable HCV RNA and later broke through or relapsed. These patients had significantly (P = .003) fewer clinical outcomes whether randomized to maintenance therapy or control. Following randomization, serum HCV RNA increased significantly in all 90 control patients and in 58 of 88 receiving maintenance therapy. Only 30 patients had persistent suppression of HCV RNA by ≥4 log10 during maintenance therapy. No significant reduction in clinical outcomes was observed in these patients. Conclusions: Viral suppression by ≥4 log10 with full-dose peginterferon/ribavirin is associated with a significant reduction in clinical outcomes. Continuing low-dose peginterferon maintenance therapy, even in patients with persistent viral suppression, does not lead to a further decline in clinical outcomes.",
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AU - Shiffman, Mitchell L.

AU - Morishima, Chihiro

AU - Dienstag, Jules L.

AU - Lindsay, Karen L.

AU - Hoefs, John C.

AU - Lee, William M.

AU - Wright, Elizabeth C.

AU - Naishadham, Deepa

AU - Everson, Gregory T.

AU - Lok, Anna S.

AU - Di Bisceglie, Adrian M.

AU - Bonkovsky, Herbert L.

AU - Ghany, Marc G.

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Y1 - 2009/12

N2 - Background & Aims: The Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial demonstrated that low-dose peginterferon maintenance therapy was ineffective in preventing clinical outcomes in patients with chronic hepatitis C, advanced fibrosis, and failure to achieve a sustained virologic response during lead-in phase treatment with standard dose peginterferon/ribavirin. This analysis was performed to determine whether suppressing HCV RNA during the trial was associated with a reduction in clinical outcomes. Methods: Seven hundred sixty-four patients treated during the lead-in phase of HALT-C trial were randomized to either peginterferon alfa-2a (90 μg/week) maintenance therapy or no treatment (control) for 3.5 years. Clinical outcomes included an increase in Child-Turcotte-Pugh score, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage, hepatocellular carcinoma, and mortality. Results: During the lead-in, ≥4-log10 decline in serum HCV RNA occurred in 178 patients; 82% of whom lost detectable HCV RNA and later broke through or relapsed. These patients had significantly (P = .003) fewer clinical outcomes whether randomized to maintenance therapy or control. Following randomization, serum HCV RNA increased significantly in all 90 control patients and in 58 of 88 receiving maintenance therapy. Only 30 patients had persistent suppression of HCV RNA by ≥4 log10 during maintenance therapy. No significant reduction in clinical outcomes was observed in these patients. Conclusions: Viral suppression by ≥4 log10 with full-dose peginterferon/ribavirin is associated with a significant reduction in clinical outcomes. Continuing low-dose peginterferon maintenance therapy, even in patients with persistent viral suppression, does not lead to a further decline in clinical outcomes.

AB - Background & Aims: The Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial demonstrated that low-dose peginterferon maintenance therapy was ineffective in preventing clinical outcomes in patients with chronic hepatitis C, advanced fibrosis, and failure to achieve a sustained virologic response during lead-in phase treatment with standard dose peginterferon/ribavirin. This analysis was performed to determine whether suppressing HCV RNA during the trial was associated with a reduction in clinical outcomes. Methods: Seven hundred sixty-four patients treated during the lead-in phase of HALT-C trial were randomized to either peginterferon alfa-2a (90 μg/week) maintenance therapy or no treatment (control) for 3.5 years. Clinical outcomes included an increase in Child-Turcotte-Pugh score, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage, hepatocellular carcinoma, and mortality. Results: During the lead-in, ≥4-log10 decline in serum HCV RNA occurred in 178 patients; 82% of whom lost detectable HCV RNA and later broke through or relapsed. These patients had significantly (P = .003) fewer clinical outcomes whether randomized to maintenance therapy or control. Following randomization, serum HCV RNA increased significantly in all 90 control patients and in 58 of 88 receiving maintenance therapy. Only 30 patients had persistent suppression of HCV RNA by ≥4 log10 during maintenance therapy. No significant reduction in clinical outcomes was observed in these patients. Conclusions: Viral suppression by ≥4 log10 with full-dose peginterferon/ribavirin is associated with a significant reduction in clinical outcomes. Continuing low-dose peginterferon maintenance therapy, even in patients with persistent viral suppression, does not lead to a further decline in clinical outcomes.

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