Reduction in hepatic inflammation is associated with less fibrosis progression and fewer clinical outcomes in advanced hepatitis c

Chihiro Morishima, Mitchell L. Shiffman, Jules L. Dienstag, Karen L. Lindsay, G. Szabó, Gregory T. Everson, Anna S. Lok, Adrian M. Di Bisceglie, Marc G. Ghany, Deepa Naishadham, Timothy R. Morgan, Elizabeth C. Wright

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

OBJECTIVES:During the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial, 3.5 years of maintenance peginterferon-alfa-2a therapy did not affect liver fibrosis progression or clinical outcomes among 1,050 previous interferon nonresponders with advanced fibrosis or cirrhosis. We investigated whether reduced hepatic inflammation was associated with clinical benefit in 834 patients with a baseline and follow-up biopsy 1.5 years after randomization to peginterferon or observation.METHODS:Relationships between change in hepatic inflammation (Ishak hepatic activity index, (HAI)) and serum alanine aminotransferase level, fibrosis progression and clinical outcomes after randomization, and hepatitis C virus (HCV) RNA decline before and after randomization were evaluated. Histological change was defined as a 2-point difference in HAI or Ishak fibrosis score between biopsies.RESULTS:Among 657 patients who received full-dose peginterferon/ribavirin lead-in therapy before randomization, year-1.5 HAI improvement was associated with lead-in HCV RNA suppression in both the randomized treated (P0.0001) and control (P0.0001) groups, even in the presence of recurrent viremia. This relationship persisted at year 3.5 in both the treated (P0.001) and control (P0.01) groups. Among 834 patients followed for a median of 6 years, fewer clinical outcomes occurred in patients with improved HAI at year 1.5 compared with those without such improvement in both the treated (P0.03) and control (P0.05) groups. Among patients with Ishak 3-4 fibrosis at baseline, those with improved HAI at year 1.5 had less fibrosis progression at year 1.5 in both the treated (P0.0003) and control (P0.02) groups.CONCLUSIONS:Reduced hepatic inflammation (measured 1.5 and 3.5 years after randomization) was associated with profound virological suppression during lead-in treatment with full-dose peginterferon/ribavirin and with decreased fibrosis progression and clinical outcomes, independent of randomized treatment.

Original languageEnglish
Pages (from-to)1388-1398
Number of pages11
JournalAmerican Journal of Gastroenterology
Volume107
Issue number9
DOIs
Publication statusPublished - Sep 2012

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Hepatitis
Fibrosis
Inflammation
Random Allocation
Liver
Control Groups
Ribavirin
Hepacivirus
RNA
Biopsy
Therapeutics
Viremia
Hepatitis C
Alanine Transaminase
Liver Cirrhosis
Interferons
Antiviral Agents
Maintenance
Observation
Serum

ASJC Scopus subject areas

  • Gastroenterology

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Reduction in hepatic inflammation is associated with less fibrosis progression and fewer clinical outcomes in advanced hepatitis c. / Morishima, Chihiro; Shiffman, Mitchell L.; Dienstag, Jules L.; Lindsay, Karen L.; Szabó, G.; Everson, Gregory T.; Lok, Anna S.; Di Bisceglie, Adrian M.; Ghany, Marc G.; Naishadham, Deepa; Morgan, Timothy R.; Wright, Elizabeth C.

In: American Journal of Gastroenterology, Vol. 107, No. 9, 09.2012, p. 1388-1398.

Research output: Contribution to journalArticle

Morishima, C, Shiffman, ML, Dienstag, JL, Lindsay, KL, Szabó, G, Everson, GT, Lok, AS, Di Bisceglie, AM, Ghany, MG, Naishadham, D, Morgan, TR & Wright, EC 2012, 'Reduction in hepatic inflammation is associated with less fibrosis progression and fewer clinical outcomes in advanced hepatitis c', American Journal of Gastroenterology, vol. 107, no. 9, pp. 1388-1398. https://doi.org/10.1038/ajg.2012.137
Morishima, Chihiro ; Shiffman, Mitchell L. ; Dienstag, Jules L. ; Lindsay, Karen L. ; Szabó, G. ; Everson, Gregory T. ; Lok, Anna S. ; Di Bisceglie, Adrian M. ; Ghany, Marc G. ; Naishadham, Deepa ; Morgan, Timothy R. ; Wright, Elizabeth C. / Reduction in hepatic inflammation is associated with less fibrosis progression and fewer clinical outcomes in advanced hepatitis c. In: American Journal of Gastroenterology. 2012 ; Vol. 107, No. 9. pp. 1388-1398.
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abstract = "OBJECTIVES:During the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial, 3.5 years of maintenance peginterferon-alfa-2a therapy did not affect liver fibrosis progression or clinical outcomes among 1,050 previous interferon nonresponders with advanced fibrosis or cirrhosis. We investigated whether reduced hepatic inflammation was associated with clinical benefit in 834 patients with a baseline and follow-up biopsy 1.5 years after randomization to peginterferon or observation.METHODS:Relationships between change in hepatic inflammation (Ishak hepatic activity index, (HAI)) and serum alanine aminotransferase level, fibrosis progression and clinical outcomes after randomization, and hepatitis C virus (HCV) RNA decline before and after randomization were evaluated. Histological change was defined as a 2-point difference in HAI or Ishak fibrosis score between biopsies.RESULTS:Among 657 patients who received full-dose peginterferon/ribavirin lead-in therapy before randomization, year-1.5 HAI improvement was associated with lead-in HCV RNA suppression in both the randomized treated (P0.0001) and control (P0.0001) groups, even in the presence of recurrent viremia. This relationship persisted at year 3.5 in both the treated (P0.001) and control (P0.01) groups. Among 834 patients followed for a median of 6 years, fewer clinical outcomes occurred in patients with improved HAI at year 1.5 compared with those without such improvement in both the treated (P0.03) and control (P0.05) groups. Among patients with Ishak 3-4 fibrosis at baseline, those with improved HAI at year 1.5 had less fibrosis progression at year 1.5 in both the treated (P0.0003) and control (P0.02) groups.CONCLUSIONS:Reduced hepatic inflammation (measured 1.5 and 3.5 years after randomization) was associated with profound virological suppression during lead-in treatment with full-dose peginterferon/ribavirin and with decreased fibrosis progression and clinical outcomes, independent of randomized treatment.",
author = "Chihiro Morishima and Shiffman, {Mitchell L.} and Dienstag, {Jules L.} and Lindsay, {Karen L.} and G. Szab{\'o} and Everson, {Gregory T.} and Lok, {Anna S.} and {Di Bisceglie}, {Adrian M.} and Ghany, {Marc G.} and Deepa Naishadham and Morgan, {Timothy R.} and Wright, {Elizabeth C.}",
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T1 - Reduction in hepatic inflammation is associated with less fibrosis progression and fewer clinical outcomes in advanced hepatitis c

AU - Morishima, Chihiro

AU - Shiffman, Mitchell L.

AU - Dienstag, Jules L.

AU - Lindsay, Karen L.

AU - Szabó, G.

AU - Everson, Gregory T.

AU - Lok, Anna S.

AU - Di Bisceglie, Adrian M.

AU - Ghany, Marc G.

AU - Naishadham, Deepa

AU - Morgan, Timothy R.

AU - Wright, Elizabeth C.

PY - 2012/9

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N2 - OBJECTIVES:During the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial, 3.5 years of maintenance peginterferon-alfa-2a therapy did not affect liver fibrosis progression or clinical outcomes among 1,050 previous interferon nonresponders with advanced fibrosis or cirrhosis. We investigated whether reduced hepatic inflammation was associated with clinical benefit in 834 patients with a baseline and follow-up biopsy 1.5 years after randomization to peginterferon or observation.METHODS:Relationships between change in hepatic inflammation (Ishak hepatic activity index, (HAI)) and serum alanine aminotransferase level, fibrosis progression and clinical outcomes after randomization, and hepatitis C virus (HCV) RNA decline before and after randomization were evaluated. Histological change was defined as a 2-point difference in HAI or Ishak fibrosis score between biopsies.RESULTS:Among 657 patients who received full-dose peginterferon/ribavirin lead-in therapy before randomization, year-1.5 HAI improvement was associated with lead-in HCV RNA suppression in both the randomized treated (P0.0001) and control (P0.0001) groups, even in the presence of recurrent viremia. This relationship persisted at year 3.5 in both the treated (P0.001) and control (P0.01) groups. Among 834 patients followed for a median of 6 years, fewer clinical outcomes occurred in patients with improved HAI at year 1.5 compared with those without such improvement in both the treated (P0.03) and control (P0.05) groups. Among patients with Ishak 3-4 fibrosis at baseline, those with improved HAI at year 1.5 had less fibrosis progression at year 1.5 in both the treated (P0.0003) and control (P0.02) groups.CONCLUSIONS:Reduced hepatic inflammation (measured 1.5 and 3.5 years after randomization) was associated with profound virological suppression during lead-in treatment with full-dose peginterferon/ribavirin and with decreased fibrosis progression and clinical outcomes, independent of randomized treatment.

AB - OBJECTIVES:During the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial, 3.5 years of maintenance peginterferon-alfa-2a therapy did not affect liver fibrosis progression or clinical outcomes among 1,050 previous interferon nonresponders with advanced fibrosis or cirrhosis. We investigated whether reduced hepatic inflammation was associated with clinical benefit in 834 patients with a baseline and follow-up biopsy 1.5 years after randomization to peginterferon or observation.METHODS:Relationships between change in hepatic inflammation (Ishak hepatic activity index, (HAI)) and serum alanine aminotransferase level, fibrosis progression and clinical outcomes after randomization, and hepatitis C virus (HCV) RNA decline before and after randomization were evaluated. Histological change was defined as a 2-point difference in HAI or Ishak fibrosis score between biopsies.RESULTS:Among 657 patients who received full-dose peginterferon/ribavirin lead-in therapy before randomization, year-1.5 HAI improvement was associated with lead-in HCV RNA suppression in both the randomized treated (P0.0001) and control (P0.0001) groups, even in the presence of recurrent viremia. This relationship persisted at year 3.5 in both the treated (P0.001) and control (P0.01) groups. Among 834 patients followed for a median of 6 years, fewer clinical outcomes occurred in patients with improved HAI at year 1.5 compared with those without such improvement in both the treated (P0.03) and control (P0.05) groups. Among patients with Ishak 3-4 fibrosis at baseline, those with improved HAI at year 1.5 had less fibrosis progression at year 1.5 in both the treated (P0.0003) and control (P0.02) groups.CONCLUSIONS:Reduced hepatic inflammation (measured 1.5 and 3.5 years after randomization) was associated with profound virological suppression during lead-in treatment with full-dose peginterferon/ribavirin and with decreased fibrosis progression and clinical outcomes, independent of randomized treatment.

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