@article{92ba8bf6d18e4cb6b4a19385846c1833,
title = "Reliability of histologic assessment for NAFLD and development of an expanded NAFLD activity score",
abstract = "Background and Aims: The NASH Clinical Research Network histologic scoring system, the gold-standard NASH histology assessment for clinical trials, has demonstrated intrarater and interrater variability. An expert panel in a previous systematic Research and Development/University of California Los Angeles (RAND/UCLA) study determined that existing histologic scoring systems do not fully capture NASH disease activity and fibrosis, and standardized definitions of histologic features are needed. We evaluated the reliability of existing and alternate histologic measures and their correlations with a disease activity visual analog scale to propose optimal components for an expanded NAFLD activity score (NAS). Approach and Results: Four liver pathologists who were involved in the prior RAND/UCLA study underwent standardized training and multiple discussions with the goal of improving agreement. They were blinded to clinical information and scored histologic measures twice, ≥2 weeks apart, for 40 liver biopsies representing the full spectrum of NAFLD. Index intraclass correlation coefficient (ICC) estimates demonstrated intrarater (0.80–0.85) and interrater (0.60–0.72) reliability. Hepatocyte ballooning items had similar interrater ICCs (0.68–0.79), including those extending scores from 0–2 to 0–4. Steatosis measures (interrater ICCs, 0.72–0.80) correlated poorly with disease activity. Correlations with disease activity were largest for hepatocyte ballooning and Mallory-Denk bodies (MDBs), with both used to develop the expanded NAS (intrarater ICC, 0.90; interrater ICC, 0.80). Fibrosis measures had ICCs of 0.70–0.87. Conclusions: After extensive preparation among a group of experienced pathologists, we demonstrated improved reliability of multiple existing histologic NAFLD indices and fibrosis staging systems. Hepatocyte ballooning and MDBs most strongly correlated with disease activity and were used for the expanded NAS. Further validation including evaluation of responsiveness is required.",
author = "Pai, {Rish K.} and Vipul Jairath and Malcolm Hogan and Guangyong Zou and Adeyi, {Oyedele A.} and Anstee, {Quentin M.} and Aqel, {Bashar A.} and Cynthia Behling and Carey, {Elizabeth J.} and Clouston, {Andrew D.} and Kathleen Corey and Feagan, {Brian G.} and Kleiner, {David E.} and Christopher Ma and McFarlane, {Stefanie C.} and Mazen Noureddin and Vlad Ratziu and Valasek, {Mark A.} and Younossi, {Zobair M.} and Harrison, {Stephen A.} and Rohit Loomba",
note = "Funding Information: Supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health Funding Information: Dr. Anstee consults for, is on the speakers{\textquoteright} bureau for, and received grants from Allergan/Tobira. He consults for and is on the speakers{\textquoteright} bureau for BMS, Genfit, and Gilead. He consults for and received grants from AstraZeneca, Novartis Pharma, and Pfizer. He consults for 89 Bio, Alimentiv, Altimmune, Axcella, Blade, BNN Cardio, Cirius, CymaBay, EcoR1, Eli Lilly & Company, Galmed, Genentech, Grunthal, HistoIndex, Indalo, Intercept Pharma Europe, Inventiva, IQVIA, Janssen, Johnson & Johnson, Madrigal, MedImmune, Medpace, Metacrine, NGMBio, North Sea Therapeutics, Novo Nordisk, Path AI, Poxel, ProSciento, Raptor Pharma, Roche, Servier, Shionogi, Terns, The Medicines Company, and Viking Therapeutics. He is on the speakers{\textquoteright} bureau for Abbott Laboratories, Clinical Care Options, Falk, Fishawack, Integritas Communications, Kenes, and Medscape. He received grants from GlaxoSmithKline and Glympse Bio. He receives royalties from Elsevier Ltd. He is a coordinator of the EU IMI‐2 LITMUS consortium, which is funded by the EU Horizon 2020 programme and EFPIA. This multistakeholder consortium includes industry partners. Dr. Behling is employed by and owns stock in Pacific Rim Pathology Lab. She consults for Pfizer. Dr. Corey advises Novo Nordisk, Theratechnologies, and BMS. Dr. Feagan is employed by Alimentiv. Dr. Harrison consults, advises, received grants from, and owns stock in Akero Therapeutics, Galectin Therapeutics, Genfit Corp, Hepion Pharmaceuticals, Metacrine, NGM Biopharmaceuticals, and Northsea Therapeutics. He consults, advises, and received grants from Axcella Health, Cymabay Therapeutics, Hightide Therapeutics, Intercept Pharmaceuticals, Madrigal Pharmaceuticals, Novo Nordisk, Poxel, and Sagimet Biosciences. He consults, advises, and owns stock in HistoIndex, Medpace, and Sonic Incytes Medican Corp. He advises and owns stock in Chronwell. He received grants from and owns stock in Cirius Therapeutics. He consults and advises Altimmune, Echosens North America, Foresite Labs, Prometic Pharma, Ridgeline, and Terns. He advises and received grants from CiVI Biopharma, Galmed Research & Dev, Gilead Sciences, and Novartis Pharmaceuticals. He consults and received grants from Enyo Pharma and Viking Therapeutics. He consults for AgomAB, Alentic Therapeutics, Alimentiv, Boston Pharmaceutics, B Riley FBR, BVF Partners, Cohbar, Canfite, Corcept Therapeutics, Fibronostics, Fortress Biotech, GNS, Inipharm, Ionis, Kowa Research Institute, Microba, Nutrasource, Perspectum Diagnostics, and Poper Sandler. He advises 89 Bio, Arrowhead, Indalo, Path AI, and Theratechnologies. Dr. Jairath is employed by Alimentiv. Dr. Loomba serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol‐Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Terns Pharmaceuticals, and Viking Therapeutics. In addition, his institutions received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer‐Ingelheim, Bristol‐Myers Squibb, Eli Lilly, Galectin Therapeutics, Galmed Pharmaceuticals, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Novo Nordisk, Merck, Pfizer, Sonic Incytes, and Terns Pharmaceuticals. He is a co‐founder of LipoNexus Inc. Dr. Ma consults for, is on the speakers{\textquoteright} bureau, and received grants from Ferring and Pfizer. He consults and is on the speakers{\textquoteright} bureau for AbbVie, Alimentiv, Janssen, and Takeda. He consults for Amgen, AVIR< BioJAMP, BMS< Fresenius Kabi, McKesson, Mylan, and Pendopharm. Ms. McFarlane is employed by Alimentiv. Dr. Noureddin received grants from and owns stock in Viking. He consults for and received grants from Gilead, Pfizer, and Madrigal. He consults for 89 Bio, Altimmune, cohBar, Cytodyn, Intercept, NovoNordisk, Blad, EchoSens, Fractyl, NorthSea, Terns, Siemens, and Roche. He received grants from Allergan, BMS, Galmed, Galectin, Genfit, Conatus, Enanta, Novartis, Shire, and Zydus. He owns stock in Anaetos and Rivus Pharma. He owns intellectual property rights in the MAST score. Dr. Pai consults for Alimentiv. Dr. Younossi consults for Gilead, Intercept, Terns, NovoNordisk, Merck, Quest, and Siemens. Publisher Copyright: {\textcopyright} 2022 American Association for the Study of Liver Diseases.",
year = "2022",
month = oct,
doi = "10.1002/hep.32475",
language = "English (US)",
volume = "76",
pages = "1150--1163",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "4",
}