Ductular reaction in hereditary hemochromatosis: The link between hepatocyte senescence and fibrosis progression

Wood, Marnie J, Gadd, Victoria L., Powell, Lawrie W., Ramm, Grant A. and Clouston, Andrew D. (2014) Ductular reaction in hereditary hemochromatosis: The link between hepatocyte senescence and fibrosis progression. Hepatology, 59 3: 848-857. doi:10.1002/hep.26706

Author Wood, Marnie J
Gadd, Victoria L.
Powell, Lawrie W.
Ramm, Grant A.
Clouston, Andrew D.
Title Ductular reaction in hereditary hemochromatosis: The link between hepatocyte senescence and fibrosis progression
Journal name Hepatology   Check publisher's open access policy
ISSN 0270-9139
Publication date 2014-03-01
Year available 2014
Sub-type Article (original research)
DOI 10.1002/hep.26706
Open Access Status Not Open Access
Volume 59
Issue 3
Start page 848
End page 857
Total pages 10
Place of publication Hoboken, United States
Publisher John Wiley & Sons
Language eng
Formatted abstract
The development of portal fibrosis following the iron loading of hepatocytes is the first stage of fibrogenesis in hereditary hemochromatosis. In other chronic liver diseases it has been shown that a ductular reaction (DR) appears early, correlates with fibrosis progression, and is a consequence of activation of an alternative pathway of hepatocyte replication. This study was designed to investigate the presence of the DR in hemochromatosis and describe its associations. Liver biopsies from 63 C282Y homozygous patients were assessed for hepatic iron concentration (HIC) and graded for iron loading, fibrosis stage, steatosis, and inflammation. Immunostaining allowed quantification of the DR, hepatocyte senescence and proliferation, and analysis incorporated clinical data. Hepatocyte senescence was positively correlated with HIC, serum ferritin, and oxidative stress. A DR was demonstrated and occurred prior to histological fibrosis. HIC, age, hepatocyte senescence and proliferation, portal inflammation, and excessive alcohol consumption all had significant associations with the extent of the DR. In multivariate analysis, iron loading, hepatocyte replicative arrest, and portal inflammation remained independently and significantly associated with the DR. Of factors associated with fibrosis progression, the DR (odds ratio [OR] 10.86 P<0.0001) and the presence of portal inflammation (OR 4.31, P=0.028) remained significant after adjustment for cofactors. The extent of the DR regressed following therapeutic venesection. Conclusion: Iron loading of hepatocytes leads to impaired replication, stimulating the development of the DR in hemochromatosis and this correlates strongly with hepatic fibrosis. Portal inflammation occurs in hemochromatosis and is independently associated with the DR and fibrosis, and thus its role in this disease should be evaluated further. (Hepatology 2014;59:848-857).
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2015 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 24 times in Thomson Reuters Web of Science Article | Citations
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