DOI: 10.1002/hep.510290623. Effects of Iron Loading on Pathogenicity in Hepatitis C Virus-Infected Chimpanzees

Effects of Iron Loading on Pathogenicity in Hepatitis C Virus-Infected Chimpanzees

10.1002/hep.510290623

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Hepatology (276)

Abstract

Elevated iron levels have been associated with raised serum alanine transaminase (ALT) levels in hepatitis C virus (HCV)–infected humans. However, it is not clear if HCV infection causes increased iron accumulation by the liver or if the severity of HCV infection is actually worsened by higher iron levels in the host. To better understand the relationship between iron and persistent HCV infections, we examined the effect of excess dietary iron on disease severity in HCV–infected chimpanzees. Iron was supplemented in the diets of four HCV–infected and two uninfected chimpanzees for 29 weeks to achieve iron loading. Iron loading was confirmed by increases in serum iron levels, percentages of transferrin saturation, ferritin levels, elevations in hepatic iron concentration (HIC), and by histological examination. The majority of HCV–infected chimpanzees had higher iron levels before iron feeding than the uninfected animals. Although various degrees of iron loading occurred in all chimpanzees, HCV–infected animals exhibited increased loading in comparison with uninfected animals. The effects of iron loading on HCV disease expression was determined by comparing disease parameters during an extended baseline period before iron loading with the period during iron loading and immediately following iron loading. Iron loading did not influence the viral load, but did exacerbate liver injury in HCV–infected chimpanzees, as evidenced by elevated ALT and histological changes. Because all chimpanzees on high iron diets experienced iron loading, but pathological effects were only observed in HCV–infected chimpanzees, HCV infection appears to increase the susceptibility of the liver to injury following iron loading. These results confirm and extend previous observations made in human populations and serve to further validate the chimpanzee model of chronic hepatitis C.

Bibliography

Bassett, S. E., Di Bisceglie, A. M., Bacon, B. R., Sharp, M. R., Govindarajan, S., Hubbard, G. B., Brasky, K. M., & Lanford, R. E. (1999). Effects of Iron Loading on Pathogenicity in Hepatitis C Virus-Infected Chimpanzees. Hepatology, 29(6), 1884â1892.

Authors 8

Suzanne E. Bassett (first)
Adrian M. Di Bisceglie (additional)
Bruce R. Bacon (additional)
Mark R. Sharp (additional)
Sugantha Govindarajan (additional)
Gene B. Hubbard (additional)
Kathleen M. Brasky (additional)
Robert E. Lanford (additional)

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Dates

Type	When
Created	21 years, 1 month ago (July 28, 2004, 3:25 a.m.)
Deposited	9 months ago (Dec. 1, 2024, 6:29 a.m.)
Indexed	3 months, 4 weeks ago (May 4, 2025, 12:06 a.m.)
Issued	26 years, 3 months ago (June 1, 1999)
Published	26 years, 3 months ago (June 1, 1999)
Published Print	26 years, 3 months ago (June 1, 1999)

Funders 0

None

BibTeX

@article{Bassett_1999, title={Effects of Iron Loading on Pathogenicity in Hepatitis C Virus-Infected Chimpanzees}, volume={29}, ISSN={0270-9139}, url={http://dx.doi.org/10.1002/hep.510290623}, DOI={10.1002/hep.510290623}, number={6}, journal={Hepatology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Bassett, Suzanne E. and Di Bisceglie, Adrian M. and Bacon, Bruce R. and Sharp, Mark R. and Govindarajan, Sugantha and Hubbard, Gene B. and Brasky, Kathleen M. and Lanford, Robert E.}, year={1999}, month=jun, pages={1884–1892} }

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  "abstract": "<jats:sec>\n            <jats:title/>\n            <jats:p>Elevated iron levels have been associated with raised serum alanine transaminase (ALT) levels in hepatitis C virus (HCV)\u2013infected humans. However, it is not clear if HCV infection causes increased iron accumulation by the liver or if the severity of HCV infection is actually worsened by higher iron levels in the host. To better understand the relationship between iron and persistent HCV infections, we examined the effect of excess dietary iron on disease severity in HCV\u2013infected chimpanzees. Iron was supplemented in the diets of four HCV\u2013infected and two uninfected chimpanzees for 29 weeks to achieve iron loading. Iron loading was confirmed by increases in serum iron levels, percentages of transferrin saturation, ferritin levels, elevations in hepatic iron concentration (HIC), and by histological examination. The majority of HCV\u2013infected chimpanzees had higher iron levels before iron feeding than the uninfected animals. Although various degrees of iron loading occurred in all chimpanzees, HCV\u2013infected animals exhibited increased loading in comparison with uninfected animals. The effects of iron loading on HCV disease expression was determined by comparing disease parameters during an extended baseline period before iron loading with the period during iron loading and immediately following iron loading. Iron loading did not influence the viral load, but did exacerbate liver injury in HCV\u2013infected chimpanzees, as evidenced by elevated ALT and histological changes. Because all chimpanzees on high iron diets experienced iron loading, but pathological effects were only observed in HCV\u2013infected chimpanzees, HCV infection appears to increase the susceptibility of the liver to injury following iron loading. These results confirm and extend previous observations made in human populations and serve to further validate the chimpanzee model of chronic hepatitis C.</jats:p>\n          </jats:sec>",
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