Reliability of histologic assessment for NAFLD and development of an expanded NAFLD activity score

Rish K. Pai; Vipul Jairath; Malcolm Hogan; Guangyong Zou; Oyedele A. Adeyi; Quentin M. Anstee; Bashar A. Aqel; Cynthia Behling; Elizabeth J. Carey; Andrew D. Clouston; Kathleen Corey; Brian G. Feagan; David E. Kleiner; Christopher Ma; Stefanie C. McFarlane; Mazen Noureddin; Vlad Ratziu; Mark A. Valasek; Zobair M. Younossi; Stephen A. Harrison; Rohit Loomba

doi:10.1002/hep.32475

Reliability of histologic assessment for NAFLD and development of an expanded NAFLD activity score

Rish K. Pai, Vipul Jairath, Malcolm Hogan, Guangyong Zou, Oyedele A. Adeyi, Quentin M. Anstee, Bashar A. Aqel, Cynthia Behling, Elizabeth J. Carey, Andrew D. Clouston, Kathleen Corey, Brian G. Feagan, David E. Kleiner, Christopher Ma, Stefanie C. McFarlane, Mazen Noureddin, Vlad Ratziu, Mark A. Valasek, Zobair M. Younossi, Stephen A. HarrisonRohit Loomba

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	1150-1163
Number of pages	14
Journal	Hepatology
Volume	76
Issue number	4
DOIs	https://doi.org/10.1002/hep.32475
State	Published - Oct 2022

ASJC Scopus subject areas

Hepatology

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10.1002/hep.32475

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Pai, R. K., Jairath, V., Hogan, M., Zou, G., Adeyi, O. A., Anstee, Q. M., Aqel, B. A., Behling, C., Carey, E. J., Clouston, A. D., Corey, K., Feagan, B. G., Kleiner, D. E., Ma, C., McFarlane, S. C., Noureddin, M., Ratziu, V., Valasek, M. A., Younossi, Z. M., ... Loomba, R. (2022). Reliability of histologic assessment for NAFLD and development of an expanded NAFLD activity score. Hepatology, 76(4), 1150-1163. https://doi.org/10.1002/hep.32475

Pai, RK, Jairath, V, Hogan, M, Zou, G, Adeyi, OA, Anstee, QM, Aqel, BA, Behling, C, Carey, EJ, Clouston, AD, Corey, K, Feagan, BG, Kleiner, DE, Ma, C, McFarlane, SC, Noureddin, M, Ratziu, V, Valasek, MA, Younossi, ZM, Harrison, SA & Loomba, R 2022, 'Reliability of histologic assessment for NAFLD and development of an expanded NAFLD activity score', Hepatology, vol. 76, no. 4, pp. 1150-1163. https://doi.org/10.1002/hep.32475

@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 = "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",

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TY - JOUR

T1 - Reliability of histologic assessment for NAFLD and development of an expanded NAFLD activity score

AU - Pai, Rish K.

AU - Jairath, Vipul

AU - Hogan, Malcolm

AU - Zou, Guangyong

AU - Adeyi, Oyedele A.

AU - Anstee, Quentin M.

AU - Aqel, Bashar A.

AU - Behling, Cynthia

AU - Carey, Elizabeth J.

AU - Clouston, Andrew D.

AU - Corey, Kathleen

AU - Feagan, Brian G.

AU - Kleiner, David E.

AU - Ma, Christopher

AU - McFarlane, Stefanie C.

AU - Noureddin, Mazen

AU - Ratziu, Vlad

AU - Valasek, Mark A.

AU - Younossi, Zobair M.

AU - Harrison, Stephen A.

AU - Loomba, Rohit

PY - 2022/10

Y1 - 2022/10

N2 - 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.

AB - 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.

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U2 - 10.1002/hep.32475

DO - 10.1002/hep.32475

M3 - Article

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VL - 76

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EP - 1163

JO - Hepatology

JF - Hepatology

IS - 4

ER -

Reliability of histologic assessment for NAFLD and development of an expanded NAFLD activity score

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