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

Overview of attention for article published in Hepatology, January 2014
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Title
Ductular reaction in hereditary hemochromatosis: The link between hepatocyte senescence and fibrosis progression
Published in
Hepatology, January 2014
DOI 10.1002/hep.26706
Pubmed ID
Authors

Marnie J. Wood, Victoria L. Gadd, Lawrie W. Powell, Grant A. Ramm, Andrew D. Clouston

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.

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The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 37 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 24%
Student > Doctoral Student 4 11%
Student > Bachelor 4 11%
Student > Master 4 11%
Researcher 3 8%
Other 6 16%
Unknown 7 19%
Readers by discipline Count As %
Medicine and Dentistry 14 38%
Agricultural and Biological Sciences 8 22%
Biochemistry, Genetics and Molecular Biology 5 14%
Engineering 1 3%
Unknown 9 24%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 October 2016.
All research outputs
#16,046,765
of 25,371,288 outputs
Outputs from Hepatology
#6,899
of 9,093 outputs
Outputs of similar age
#187,241
of 322,854 outputs
Outputs of similar age from Hepatology
#65
of 116 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 9,093 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.4. This one is in the 21st percentile – i.e., 21% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 322,854 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 116 others from the same source and published within six weeks on either side of this one. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.