Hepatic elastin content is predictive of adverse outcome in advanced fibrotic liver disease

Aims. Needle biopsy remains essential for diagnosis in assessment of liver disease, although there remains associated risk. Examination is largely limited to subjective evaluation and biopsies are not exploited to provide personalised prognostic information. Elastin is a durable component of fibroti...

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Main Authors: Kendall, Timothy, Dolman, Grace, Duff, Catherine, Paish, Emma C., Zaitoun, Abed, Irving, William L., Fallowfield, Jonathan A., Guha, Indra Neil
Format: Article
Published: Wiley 2018
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Online Access:https://eprints.nottingham.ac.uk/50272/
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author Kendall, Timothy
Dolman, Grace
Duff, Catherine
Paish, Emma C.
Zaitoun, Abed
Irving, William L.
Fallowfield, Jonathan A.
Guha, Indra Neil
author_facet Kendall, Timothy
Dolman, Grace
Duff, Catherine
Paish, Emma C.
Zaitoun, Abed
Irving, William L.
Fallowfield, Jonathan A.
Guha, Indra Neil
author_sort Kendall, Timothy
building Nottingham Research Data Repository
collection Online Access
description Aims. Needle biopsy remains essential for diagnosis in assessment of liver disease, although there remains associated risk. Examination is largely limited to subjective evaluation and biopsies are not exploited to provide personalised prognostic information. Elastin is a durable component of fibrotic matrix in chronic disease, conferring resistance to remodelling and potentially influencing tissue biomechanics linked to portal hypertension. We hypothesised that elastin content was predictive of clinical outcome and so could be quantified to increase the beneficial information yield from a liver biopsy. Methods and results. Elastin content in liver biopsies was determined by image analysis, technically validated in an independent centre, and correlated with outcome in patients with advanced (Ishak stage ≥ 5) chronic hepatitis C virus-related chronic liver disease. Elastin was robustly quantified in an operator- and laboratory-independent manner, with very strong correlation of elastin staining measured by two methods of image classification (rs = 0.873, p < 0.00001). Elastin content (but not absolute scar content or Ishak stage) was predictive for future clinical outcomes. In a cohort of patients without sustained virologic response, median hepatic elastin content was 3.4%, and 17 patients (57%) progressed to a liver-related clinical outcome; 11 of the 15 patients (73%) with hepatic elastin >3.4% progressed to a clinical outcome, compared to only 6 out of 15 (40%) with elastin <3.4%. The difference in time to outcome was significant. Conclusions. We describe a simple and reproducible method for elastin quantification in liver biopsies that provides potentially valuable prognostic information to inform clinical management.
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spelling nottingham-502722024-08-15T15:30:52Z https://eprints.nottingham.ac.uk/50272/ Hepatic elastin content is predictive of adverse outcome in advanced fibrotic liver disease Kendall, Timothy Dolman, Grace Duff, Catherine Paish, Emma C. Zaitoun, Abed Irving, William L. Fallowfield, Jonathan A. Guha, Indra Neil Aims. Needle biopsy remains essential for diagnosis in assessment of liver disease, although there remains associated risk. Examination is largely limited to subjective evaluation and biopsies are not exploited to provide personalised prognostic information. Elastin is a durable component of fibrotic matrix in chronic disease, conferring resistance to remodelling and potentially influencing tissue biomechanics linked to portal hypertension. We hypothesised that elastin content was predictive of clinical outcome and so could be quantified to increase the beneficial information yield from a liver biopsy. Methods and results. Elastin content in liver biopsies was determined by image analysis, technically validated in an independent centre, and correlated with outcome in patients with advanced (Ishak stage ≥ 5) chronic hepatitis C virus-related chronic liver disease. Elastin was robustly quantified in an operator- and laboratory-independent manner, with very strong correlation of elastin staining measured by two methods of image classification (rs = 0.873, p < 0.00001). Elastin content (but not absolute scar content or Ishak stage) was predictive for future clinical outcomes. In a cohort of patients without sustained virologic response, median hepatic elastin content was 3.4%, and 17 patients (57%) progressed to a liver-related clinical outcome; 11 of the 15 patients (73%) with hepatic elastin >3.4% progressed to a clinical outcome, compared to only 6 out of 15 (40%) with elastin <3.4%. The difference in time to outcome was significant. Conclusions. We describe a simple and reproducible method for elastin quantification in liver biopsies that provides potentially valuable prognostic information to inform clinical management. Wiley 2018-07-31 Article PeerReviewed Kendall, Timothy, Dolman, Grace, Duff, Catherine, Paish, Emma C., Zaitoun, Abed, Irving, William L., Fallowfield, Jonathan A. and Guha, Indra Neil (2018) Hepatic elastin content is predictive of adverse outcome in advanced fibrotic liver disease. Histopathology, 73 (1). pp. 90-100. ISSN 1365-2559 cirrhosis; prognosis; hepatitis C virus; elastin http://onlinelibrary.wiley.com/doi/10.1111/his.13499/full doi:10.1111/his.13499 doi:10.1111/his.13499
spellingShingle cirrhosis; prognosis; hepatitis C virus; elastin
Kendall, Timothy
Dolman, Grace
Duff, Catherine
Paish, Emma C.
Zaitoun, Abed
Irving, William L.
Fallowfield, Jonathan A.
Guha, Indra Neil
Hepatic elastin content is predictive of adverse outcome in advanced fibrotic liver disease
title Hepatic elastin content is predictive of adverse outcome in advanced fibrotic liver disease
title_full Hepatic elastin content is predictive of adverse outcome in advanced fibrotic liver disease
title_fullStr Hepatic elastin content is predictive of adverse outcome in advanced fibrotic liver disease
title_full_unstemmed Hepatic elastin content is predictive of adverse outcome in advanced fibrotic liver disease
title_short Hepatic elastin content is predictive of adverse outcome in advanced fibrotic liver disease
title_sort hepatic elastin content is predictive of adverse outcome in advanced fibrotic liver disease
topic cirrhosis; prognosis; hepatitis C virus; elastin
url https://eprints.nottingham.ac.uk/50272/
https://eprints.nottingham.ac.uk/50272/
https://eprints.nottingham.ac.uk/50272/