Standardising the interpretation of liver biopsies in non-alcoholic fatty liver disease clinical trials

Rish K. Pai, David E. Kleiner, John Hart, Oyedele A. Adeyi, Andrew D. Clouston, Cynthia A. Behling, Dhanpat Jain, Sanjay Kakar, Mayur Brahmania, Lawrence Burgart, Kenneth P. Batts, Mark A. Valasek, Michael S. Torbenson, Maha Guindi, Hanlin L. Wang, Veeral Ajmera, Leon A. Adams, Claire E. Parker, Brian G. Feagan, Rohit LoombaVipul Jairath

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Background There is substantial variation in how histologic definitions and scoring systems of non-alcoholic fatty liver disease (NAFLD) are operationalised. Aim To develop a consensus-based framework for standardising histologic assessment of liver biopsies in clinical trials of NAFLD. Methods An expert panel of 14 liver pathologists and three hepatologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 130 items derived from literature review and expert opinion were rated by each panel member on a 1-9 scale. Disagreement was defined as >= 5 ratings in the lowest (1-3) and highest (7-9) categories. Items were classified as inappropriate (median 1-3.5 without disagreement), uncertain (median 3.5-6.5 or any median with disagreement) or appropriate (median 6.5-9 without disagreement). Survey results were discussed as a group before voting. Results Current measures of disease activity and fibrosis may not fully capture important features of non-alcoholic steatohepatitis (NASH). Alternative methods to evaluate ballooning degeneration are needed. Panellists were uncertain whether portal inflammation, degree of steatosis and Mallory-Denk bodies are important measures of disease activity. Furthermore, it was felt that current staging systems do not capture the full spectrum of fibrosis in NASH. A consensus definition and sub-stages for bridging fibrosis are needed. The severity of perisinusoidal fibrosis should be captured at all stages. Lastly, a method to evaluate features of fibrosis regression should be developed. Conclusion The operating properties of the modifications proposed should be evaluated prospectively to determine reliability and responsiveness.

Original languageEnglish
Pages (from-to)1100-1111
Number of pages12
JournalAlimentary pharmacology & therapeutics
Issue number10
Publication statusPublished - Nov 2019

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