Evolution of hepatic steatosis in patients with advanced hepatitis C: Results from the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) trial

Anna S. Lok, James E. Everhart, Raymong T. Chung, Hae Young Kim, Gregory T. Everson, John C. Hoefs, Joel K. Greenson, Richard K. Sterling, Karen L. Lindsay, William M. Lee, Adrian M. Di Bisceglie, Herbert L. Bonkovsky, Marc G. Ghany, Chihiro Morishima

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Abstract

Hepatic steatosis is a common histologic feature in patients with chronic hepatitis C (CHC) but there are no large longitudinal studies describing the progression of steatosis in CHC. We examined changes in steatosis on serial biopsies among CHC patients participating in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. All 1050 patients in the trial had advanced fibrosis at baseline biopsy and were documented not to have had a sustained virological response to peginterferon and ribavirin. Most (94%) patients had genotype 1 infection. At least one protocol follow-up biopsy was read on 892 patients, and 699 had the last biopsy performed 3.5 years after randomization. At enrollment, 39% had cirrhosis and 61% had bridging fibrosis; 18%, 41%, 31%, and 10% had steatosis scores of 0, 1, 2, and 3 or 4, respectively. The mean steatosis score decreased in the follow-up biopsies in both the interferon-treated patients and controls with no effect of treatment assignment (P = 0.66). A decrease in steatosis score by ≥1 point was observed in 30% of patients and was associated with both progression to cirrhosis and continued presence of cirrhosis (P = 0.02). Compared to patients without a decrease in steatosis, those with a decrease in steatosis had worse metabolic parameters at enrollment, and were more likely to have a decrease in alcohol intake, improvement in metabolic parameters, and worsening liver disease (cirrhosis, esophageal varices, and deterioration in liver function). Conclusion: Serial biopsies demonstrated that in patients with CHC, steatosis recedes during progression from advanced fibrosis to cirrhosis. Decreased alcohol intake and improved metabolic parameters are associated with a decline in steatosis and may modulate hepatitis C progression.

Original languageEnglish (US)
Pages (from-to)1828-1837
Number of pages10
JournalHepatology
Volume49
Issue number6
DOIs
StatePublished - Jun 2009

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Hepatitis C
Antiviral Agents
Fibrosis
Liver
Chronic Hepatitis C
Biopsy
Therapeutics
Alcohols
Esophageal and Gastric Varices
Ribavirin
Random Allocation
Liver Cirrhosis
Interferons
Longitudinal Studies
Liver Diseases
Genotype
Infection

ASJC Scopus subject areas

  • Hepatology

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Evolution of hepatic steatosis in patients with advanced hepatitis C : Results from the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) trial. / Lok, Anna S.; Everhart, James E.; Chung, Raymong T.; Kim, Hae Young; Everson, Gregory T.; Hoefs, John C.; Greenson, Joel K.; Sterling, Richard K.; Lindsay, Karen L.; Lee, William M.; Di Bisceglie, Adrian M.; Bonkovsky, Herbert L.; Ghany, Marc G.; Morishima, Chihiro.

In: Hepatology, Vol. 49, No. 6, 06.2009, p. 1828-1837.

Research output: Contribution to journalArticle

Lok, AS, Everhart, JE, Chung, RT, Kim, HY, Everson, GT, Hoefs, JC, Greenson, JK, Sterling, RK, Lindsay, KL, Lee, WM, Di Bisceglie, AM, Bonkovsky, HL, Ghany, MG & Morishima, C 2009, 'Evolution of hepatic steatosis in patients with advanced hepatitis C: Results from the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) trial', Hepatology, vol. 49, no. 6, pp. 1828-1837. https://doi.org/10.1002/hep.22865
Lok, Anna S. ; Everhart, James E. ; Chung, Raymong T. ; Kim, Hae Young ; Everson, Gregory T. ; Hoefs, John C. ; Greenson, Joel K. ; Sterling, Richard K. ; Lindsay, Karen L. ; Lee, William M. ; Di Bisceglie, Adrian M. ; Bonkovsky, Herbert L. ; Ghany, Marc G. ; Morishima, Chihiro. / Evolution of hepatic steatosis in patients with advanced hepatitis C : Results from the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) trial. In: Hepatology. 2009 ; Vol. 49, No. 6. pp. 1828-1837.
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abstract = "Hepatic steatosis is a common histologic feature in patients with chronic hepatitis C (CHC) but there are no large longitudinal studies describing the progression of steatosis in CHC. We examined changes in steatosis on serial biopsies among CHC patients participating in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. All 1050 patients in the trial had advanced fibrosis at baseline biopsy and were documented not to have had a sustained virological response to peginterferon and ribavirin. Most (94{\%}) patients had genotype 1 infection. At least one protocol follow-up biopsy was read on 892 patients, and 699 had the last biopsy performed 3.5 years after randomization. At enrollment, 39{\%} had cirrhosis and 61{\%} had bridging fibrosis; 18{\%}, 41{\%}, 31{\%}, and 10{\%} had steatosis scores of 0, 1, 2, and 3 or 4, respectively. The mean steatosis score decreased in the follow-up biopsies in both the interferon-treated patients and controls with no effect of treatment assignment (P = 0.66). A decrease in steatosis score by ≥1 point was observed in 30{\%} of patients and was associated with both progression to cirrhosis and continued presence of cirrhosis (P = 0.02). Compared to patients without a decrease in steatosis, those with a decrease in steatosis had worse metabolic parameters at enrollment, and were more likely to have a decrease in alcohol intake, improvement in metabolic parameters, and worsening liver disease (cirrhosis, esophageal varices, and deterioration in liver function). Conclusion: Serial biopsies demonstrated that in patients with CHC, steatosis recedes during progression from advanced fibrosis to cirrhosis. Decreased alcohol intake and improved metabolic parameters are associated with a decline in steatosis and may modulate hepatitis C progression.",
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AU - Chung, Raymong T.

AU - Kim, Hae Young

AU - Everson, Gregory T.

AU - Hoefs, John C.

AU - Greenson, Joel K.

AU - Sterling, Richard K.

AU - Lindsay, Karen L.

AU - Lee, William M.

AU - Di Bisceglie, Adrian M.

AU - Bonkovsky, Herbert L.

AU - Ghany, Marc G.

AU - Morishima, Chihiro

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N2 - Hepatic steatosis is a common histologic feature in patients with chronic hepatitis C (CHC) but there are no large longitudinal studies describing the progression of steatosis in CHC. We examined changes in steatosis on serial biopsies among CHC patients participating in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. All 1050 patients in the trial had advanced fibrosis at baseline biopsy and were documented not to have had a sustained virological response to peginterferon and ribavirin. Most (94%) patients had genotype 1 infection. At least one protocol follow-up biopsy was read on 892 patients, and 699 had the last biopsy performed 3.5 years after randomization. At enrollment, 39% had cirrhosis and 61% had bridging fibrosis; 18%, 41%, 31%, and 10% had steatosis scores of 0, 1, 2, and 3 or 4, respectively. The mean steatosis score decreased in the follow-up biopsies in both the interferon-treated patients and controls with no effect of treatment assignment (P = 0.66). A decrease in steatosis score by ≥1 point was observed in 30% of patients and was associated with both progression to cirrhosis and continued presence of cirrhosis (P = 0.02). Compared to patients without a decrease in steatosis, those with a decrease in steatosis had worse metabolic parameters at enrollment, and were more likely to have a decrease in alcohol intake, improvement in metabolic parameters, and worsening liver disease (cirrhosis, esophageal varices, and deterioration in liver function). Conclusion: Serial biopsies demonstrated that in patients with CHC, steatosis recedes during progression from advanced fibrosis to cirrhosis. Decreased alcohol intake and improved metabolic parameters are associated with a decline in steatosis and may modulate hepatitis C progression.

AB - Hepatic steatosis is a common histologic feature in patients with chronic hepatitis C (CHC) but there are no large longitudinal studies describing the progression of steatosis in CHC. We examined changes in steatosis on serial biopsies among CHC patients participating in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. All 1050 patients in the trial had advanced fibrosis at baseline biopsy and were documented not to have had a sustained virological response to peginterferon and ribavirin. Most (94%) patients had genotype 1 infection. At least one protocol follow-up biopsy was read on 892 patients, and 699 had the last biopsy performed 3.5 years after randomization. At enrollment, 39% had cirrhosis and 61% had bridging fibrosis; 18%, 41%, 31%, and 10% had steatosis scores of 0, 1, 2, and 3 or 4, respectively. The mean steatosis score decreased in the follow-up biopsies in both the interferon-treated patients and controls with no effect of treatment assignment (P = 0.66). A decrease in steatosis score by ≥1 point was observed in 30% of patients and was associated with both progression to cirrhosis and continued presence of cirrhosis (P = 0.02). Compared to patients without a decrease in steatosis, those with a decrease in steatosis had worse metabolic parameters at enrollment, and were more likely to have a decrease in alcohol intake, improvement in metabolic parameters, and worsening liver disease (cirrhosis, esophageal varices, and deterioration in liver function). Conclusion: Serial biopsies demonstrated that in patients with CHC, steatosis recedes during progression from advanced fibrosis to cirrhosis. Decreased alcohol intake and improved metabolic parameters are associated with a decline in steatosis and may modulate hepatitis C progression.

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