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

Abstract

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.

Citation

Kendall, T., Dolman, G., Duff, C., Paish, E. C., Zaitoun, A., Irving, W. L., Fallowfield, J. A., & Guha, I. N. (2018). Hepatic elastin content is predictive of adverse outcome in advanced fibrotic liver disease. Histopathology, 73(1), 90-100. https://doi.org/10.1111/his.13499

• Journal Article Type: Article
• Acceptance Date: Feb 17, 2018
• Online Publication Date: Feb 21, 2018
• Publication Date: 2018-07
• Deposit Date: Mar 8, 2018
• Publicly Available Date: Mar 8, 2018
• Journal: Histopathology
• Print ISSN: 0309-0167
• Electronic ISSN: 1365-2559
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 73
• Issue: 1
• Pages: 90-100
• DOI: https://doi.org/10.1111/his.13499
• Keywords: cirrhosis; prognosis; hepatitis C virus; elastin
• Public URL: https://nottingham-repository.worktribe.com/output/948219
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1111/his.13499/full
• Additional Information: This is the peer reviewed version of the following article: Kendall, T. J., Dolman, G. E., Duff, C. M., Paish, E. C., Zaitoun, A., Irving, W., Fallowfield, J. A. and Guha, I. N. (), Hepatic elastin content is predictive of adverse outcome in advanced fibrotic liver disease. Histopathology. Accepted Author Manuscript. doi:10.1111/his.13499, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/his.13499/full. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
• Contract Date: Mar 8, 2018