TY - JOUR
T1 - Liver biopsy in the real world—reporting, expert concordance and correlation with a pragmatic clinical diagnosis
AU - TARGET-NASH Investigators
AU - Kim, Hannah P.
AU - Idowu, Michael O.
AU - Mospan, Andrea R.
AU - Allmon, Andrew G.
AU - Roden, Michael
AU - Newsome, Philip
AU - Lok, Anna S.
AU - Thuluvath, Paul J.
AU - Taunk, Jawahar
AU - Fried, Michael W.
AU - Sanyal, Arun J.
AU - Barritt, A. Sidney
AU - Abdelmalek, Manal
AU - Aguilar, Humberto
AU - Ahmed, Aijaz
AU - Allen, Alina
AU - Barlow, Sarah
AU - Barritt, Sid
AU - Bernstein, David
AU - Bhamidimarri, Kaylan
AU - Billings, Liana
AU - Brown, Kyle
AU - Brown, Robert
AU - Corbin, Karen
AU - Cusi, Kenneth
AU - deLemos, Andrew
AU - Emerick, Karan
AU - Firpi-Morell, Roberto
AU - Ghali, Maged Adel
AU - Henry, Zachary
AU - Jackson, Whitney
AU - Janardhan, Sujit
AU - Kabbany, Mohammad
AU - Kemmer, Nyingi
AU - Koch, David
AU - Kupec, Justin
AU - Landis, Charles
AU - Lawrence, Mary Katherine
AU - Levy, Cynthia
AU - Lidofsky, Steven
AU - Lok, Anna
AU - Luketic, Velimir
AU - Martinez, Enrique
AU - McClain, Craig
AU - McKiernan, Patrick
AU - Mitchell, Ellen
AU - Noureddin, Mazen
AU - Palle, Sirish
AU - Pham, Yen
AU - Pound, David
N1 - Funding Information:
: MOI is a consultant for Target RWE. ARM and AGA are employees of Target RWE. MR has served on scientific advisory boards or received speaker’s honoraria for Allergan, Boehringer‐Ingelheim Pharma, Bristol‐Myers Squibb, Eli Lilly, Fishawack Group, Gilead Sciences, Novartis Pharma, Intercept Pharma, Inventiva, Novo Nordisk, Target NASH. He is also a consultant for Terra Firma and has been involved with clinical trial research for Boehringer Ingelheim, Danone Nutricia Research and Sanofi‐Aventis. ASL has research grants from BMS, Gilead, and Target RWE. She is also an advisor/and consultant for BMS and Target RWE, and serves on the DSMB of Novo Nordisk. MWF is Chief Medical Officer for TARGET RWE and receives personal fees and is a stockholder in the company. AJS is President of Sanyal Biotechnology and has stock options in Genfit, Akarna, Tiziana, Indalo, Durect Inversago and Galmed. He has served as a consultant to Astra Zeneca, NGM Bio, Conatus, Salix, Tobira, Takeda, Jannsen, Gilead, Terns, Birdrock, 89 Bio, Siemens, Amgen, Regeneron, Alnylam, Genentech, Roche, Merck, Valeant, Boehringer‐Ingelheim, Bristol Myers Squibb, Lilly, Hemoshear, Zafgen, Novartis, Novo Nordisk, Pfizer, Exhalenz and Genfit. He has been an unpaid consultant to Intercept, Echosens, Immuron, Galectin, Fractyl, Zydus, Nordic Bioscience, Albireo, Prosciento, Surrozen. His institution has received grant support from Gilead, Salix, Tobira, Bristol Myers, Shire, Intercept, Merck, Astra Zeneca, Pfizer, Novo Nordisk, Boehringer Ingelhiem, Malinckrodt, Cumberland and Novartis. He receives royalties from Elsevier and UptoDate. ASB is a consultant for Target RWE, Pfizer Inc, and Novo Nordisk. All other authors declare that they have no conflicts of interest to disclose. Declaration of personal interests
Funding Information:
TARGET-NASH is a collaboration among academic and community investigators and the pharmaceutical industry. Target RWE is the sponsor of TARGET-NASH and is solely responsible for its content. We thank the study staff, nurses, health care providers and participants at each study centre for their contributions to this work. This research was also supported, in part, by a grant from the National Institutes of Health (T32 DK007634). TARGET-NASH Investigators are listed in Appendix 1. The authors would like to acknowledge Jonathan Durlam, Target RWE, for operational assistance related to obtaining the scanned biopsy images for analysis. Declaration of personal interests: MOI is a consultant for Target RWE. ARM and AGA are employees of Target RWE. MR has served on scientific advisory boards or received speaker’s honoraria for Allergan, Boehringer-Ingelheim Pharma, Bristol-Myers Squibb, Eli Lilly, Fishawack Group, Gilead Sciences, Novartis Pharma, Intercept Pharma, Inventiva, Novo Nordisk, Target NASH. He is also a consultant for Terra Firma and has been involved with clinical trial research for Boehringer Ingelheim, Danone Nutricia Research and Sanofi-Aventis. ASL has research grants from BMS, Gilead, and Target RWE. She is also an advisor/and consultant for BMS and Target RWE, and serves on the DSMB of Novo Nordisk. MWF is Chief Medical Officer for TARGET RWE and receives personal fees and is a stockholder in the company. AJS is President of Sanyal Biotechnology and has stock options in Genfit, Akarna, Tiziana, Indalo, Durect Inversago and Galmed. He has served as a consultant to Astra Zeneca, NGM Bio, Conatus, Salix, Tobira, Takeda, Jannsen, Gilead, Terns, Birdrock, 89 Bio, Siemens, Amgen, Regeneron, Alnylam, Genentech, Roche, Merck, Valeant, Boehringer-Ingelheim, Bristol Myers Squibb, Lilly, Hemoshear, Zafgen, Novartis, Novo Nordisk, Pfizer, Exhalenz and Genfit. He has been an unpaid consultant to Intercept, Echosens, Immuron, Galectin, Fractyl, Zydus, Nordic Bioscience, Albireo, Prosciento, Surrozen. His institution has received grant support from Gilead, Salix, Tobira, Bristol Myers, Shire, Intercept, Merck, Astra Zeneca, Pfizer, Novo Nordisk, Boehringer Ingelhiem, Malinckrodt, Cumberland and Novartis. He receives royalties from Elsevier and UptoDate. ASB is a consultant for Target RWE, Pfizer Inc, and Novo Nordisk. All other authors declare that they have no conflicts of interest to disclose.
Funding Information:
TARGET‐NASH is a collaboration among academic and community investigators and the pharmaceutical industry. Target RWE is the sponsor of TARGET‐NASH and is solely responsible for its content. We thank the study staff, nurses, health care providers and participants at each study centre for their contributions to this work. This research was also supported, in part, by a grant from the National Institutes of Health (T32 DK007634).
Publisher Copyright:
© 2021 John Wiley & Sons Ltd
PY - 2021/12
Y1 - 2021/12
N2 - Background: Patients with non-alcoholic steatohepatitis (NASH) and fibrosis stage ≥2 comprise a target population for pharmacotherapy. Liver biopsy, the reference standard for identifying this population, requires complete and accurate assessment of steatohepatitis and fibrosis. Aims. To investigate the completeness of real-world NASH-related pathology reports, assess concordance between site pathologists and central expert interpretation of the histologic elements of NASH, and determine concordance between biopsy-diagnosed NASH and a pragmatic clinical definition of NASH. Methods: Liver pathology reports from 222 patients across 38 TARGET-NASH sites were analysed for documentation of the histologic features of NASH. Biopsy slides were over-read by a blinded central expert pathologist. Concordance of histologic scores and interpretation was assessed. Histologic concordance with a clinical definition of NASH was determined. TARGET-NASH clinically defined NASH: elevated ALT, hepatic steatosis on biopsy or imaging and ≥1 of the following: BMI ≥30 kg/m2, type 2 diabetes mellitus and dyslipidaemia. Results: Documentation of steatosis, lobular inflammation, portal inflammation and ballooning were missing from 21%, 35%, 46% and 40% of reports, respectively. There was slight-to-fair concordance (weighted kappa 0.01-0.35) between site and central pathologists for inflammatory features, and moderate concordance (weighted kappa 0.56-0.57) for fibrosis staging. Clinical definition of NASH was 75%-91% concordant (94%-95% sensitive) with biopsy-diagnosed NASH. Conclusions: There is substantial variability in reporting and grading NASH and fibrosis staging in clinical practice. This heterogeneity may adversely impact patient assessment and translation of practice guidelines into reality. The TARGET-NASH pragmatic clinical definition may serve as a valuable tool to accurately identify NASH patients in clinical practice.
AB - Background: Patients with non-alcoholic steatohepatitis (NASH) and fibrosis stage ≥2 comprise a target population for pharmacotherapy. Liver biopsy, the reference standard for identifying this population, requires complete and accurate assessment of steatohepatitis and fibrosis. Aims. To investigate the completeness of real-world NASH-related pathology reports, assess concordance between site pathologists and central expert interpretation of the histologic elements of NASH, and determine concordance between biopsy-diagnosed NASH and a pragmatic clinical definition of NASH. Methods: Liver pathology reports from 222 patients across 38 TARGET-NASH sites were analysed for documentation of the histologic features of NASH. Biopsy slides were over-read by a blinded central expert pathologist. Concordance of histologic scores and interpretation was assessed. Histologic concordance with a clinical definition of NASH was determined. TARGET-NASH clinically defined NASH: elevated ALT, hepatic steatosis on biopsy or imaging and ≥1 of the following: BMI ≥30 kg/m2, type 2 diabetes mellitus and dyslipidaemia. Results: Documentation of steatosis, lobular inflammation, portal inflammation and ballooning were missing from 21%, 35%, 46% and 40% of reports, respectively. There was slight-to-fair concordance (weighted kappa 0.01-0.35) between site and central pathologists for inflammatory features, and moderate concordance (weighted kappa 0.56-0.57) for fibrosis staging. Clinical definition of NASH was 75%-91% concordant (94%-95% sensitive) with biopsy-diagnosed NASH. Conclusions: There is substantial variability in reporting and grading NASH and fibrosis staging in clinical practice. This heterogeneity may adversely impact patient assessment and translation of practice guidelines into reality. The TARGET-NASH pragmatic clinical definition may serve as a valuable tool to accurately identify NASH patients in clinical practice.
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U2 - 10.1111/apt.16674
DO - 10.1111/apt.16674
M3 - Article
C2 - 34694013
AN - SCOPUS:85121118259
SN - 0269-2813
VL - 54
SP - 1472
EP - 1480
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 11-12
ER -