Real-world evidence on non-invasive tests and associated cut-offs used to assess fibrosis in routine clinical practice.

Background & Aims

Non-invasive tests (NITs) offer a practical solution for advanced fibrosis identification in non-alcoholic fatty liver disease (NAFLD). Despite increasing implementation, their use is not standardised, which can lead to inconsistent interpretation and risk stratification. We aimed to assess the types of NITs and the corresponding cut-offs used in a range of healthcare settings.

Methods

A survey was distributed to a convenience sample of liver health experts who participated in a global NAFLD consensus statement. Respondents provided information on the NITs used in their clinic with the corresponding cut-offs and those used in established care pathways in their areas.

Results

There were 35 respondents from 24 countries, 89% of whom practised in tertiary level settings. A total of 14 different NITs were used, and each respondent reported using at least one (median = 3). Of the respondents, 80% reported using FIB-4 and liver stiffness by vibration-controlled transient elastography (Fibroscan®), followed by the NAFLD fibrosis score (49%). For FIB-4, 71% of respondents used a low cut-off of <1.3 (range <1.0 to <1.45) and 21% reported using age-specific cut-offs. For Fibroscan®, 21% of respondents used a single liver stiffness cut-off: 8 kPa in 50%, while the rest used 7.2 kPa, 7.8 kPa and 8.7 kPa. Among the 63% of respondents who used lower and upper liver stiffness cut-offs, there were variations in both values (<5 to <10 kPa and >7.5 to >20 kPa, respectively).

Conclusions

The cut-offs used for the same NITs for NAFLD risk stratification vary between clinicians. As cut-offs impact test performance, these findings underscore the heterogeneity in risk-assessment and support the importance of establishing consistent guidelines on the standardised use of NITs in NAFLD management.

Lay summary

Owing to the high prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population it is important to identify those who have more advanced stages of liver fibrosis, so that they can be properly treated. Non-invasive tests (NITs) provide a practical way to assess fibrosis risk in patients. However, we found that the cut-offs used for the same NITs vary between clinicians. As cut-offs impact test performance, these findings highlight the importance of establishing consistent guidelines on the standardised use of NITs to optimise clinical management of NAFLD.

Informations de copyright

© 2022 The Author(s).

Déclaration de conflit d'intérêts

JVL acknowledges grants and speaker fees from AbbVie, Gilead Sciences and MSD and speaker fees from Genfit, Intercept, Jannsen and ViiV, outside of the submitted work. LC has participated in advisory boards for Alexion, Echosens, MSD, Novo Nordisk, Pfizer and Sagimet and has received lecture fees from Echosens and Novo Nordisk, outside of the submitted work. AMA has received research support from Novo Nordisk, Pfizer, Target Pharma and is a consultant for Novo Nordisk and Pfizer, outside of the submitted work. LAA reports being on the advisory board for Pfizer, Roche Diagnostics and Novartis, outside of the submitted work. QMA reports Research Grant Funding: AbbVie, AstraZeneca, Boehringer Ingelheim, Glympse Bio, Intercept, Novartis, Pfizer. Consultancy on behalf of Newcastle University: Alimentiv, Akero, AstraZeneca, Axcella, 89Bio, Boehringer Ingelheim, Bristol Myers Squibb, Galmed, Genfit, Genentech, Gilead, GlaxoSmithKline, Hanmi, HistoIndex, Intercept, Inventiva, Ionis, IQVIA, Janssen, Madrigal, Medpace, Merck, NGMBio, Novartis, Novo Nordisk, PathAI, Pfizer, Poxel, Resolution Therapeutics, Roche, Ridgeline Therapeutics, RTI, Shionogi, Terns. Speaker: Fishawack, Integritas Communications, Kenes, Novo Nordisk, Madrigal, Medscape, Springer Healthcare. Royalties: Elsevier Ltd. All has been outside of the submitted work. MA has received grants from the Chilean Government: Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT 1191145) and the Comisión Nacional de Investigación Científica y Tecnológica (CONICYT, AFB170005, CARE Chile UC). All has been outside of the submitted work. EB served as a consultant or advisory board member for Boehringer Ingelheim, Gilead Sciences, Intercept, Inventiva, Merck, Novo Nordisk, Pfizer, ProSciento and a speaker for Gilead Sciences, MSD and Novo Nordisk, outside of the submitted work. MC has been on the advisory board for Target HCC, Exelixis, Galapagos and Gilead, outside of the submitted work. KC has received research support towards the University of Florida as principal investigator from Echosens, Inventiva, Novo Nordisk, Poxel, Labcorp and Zydus and is a consultant for Arrowhead, AstraZeneca, 89Bio, BMS, Lilly, Madrigal, Novo Nordisk, Quest, Sagimet, Sonic Incytes and Terns, outside of the submitted work. HH’s institution has received research grants from AstraZeneca, Echosens, Gilead, Intercept, MSD and Pfizer, outside of the submitted work. RL 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, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Novo Nordisk, Pfizer, Sonic Incytes and Terns Pharmaceuticals. He is co-founder of LipoNexus Inc. All has been outside of the submitted work. MR-G has received grants from Siemens, Gilead and Intercept. He has also served as a consultant for Abbvie, Axcella, Alpha-sigma, BMS, Allergan, Boehringer-Ingelheim, Astra-Zeneca, Gilead, Inventia, Rubió, Kaleido, Siemens, Novo-Nordisk, Shionogi, Pfizer, Sobi, Zydus, Prosciento, Shionogi, MSD and Sobi. In addition he has been lecturer in Inventia, Rubió, Sobi, Novo-Nordisk and Shionogi. He has participated in an advisory board for Galmed and has received support from AbbVie and Gilead to attend meetings. All has been outside of the submitted work. JMS reports consultant activities for Apollo Endosurgery, Albireo Pharma Inc, Bayer, BMS, Boehringer Ingelheim, Echosens, Gilead Sciences, GSK, Intercept Pharmaceuticals, Ipsen, Inventiva Pharma, Julius Clinical, Madrigal, MSD, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Siemens Healthcare GmbH. Research Funding from Gilead Sciences, Boehringer Ingelheim, Nordic Bioscience, Siemens Healthcare GmbH. Speaker Honorarium from MedPublico GmbH, Boehringer Ingelheim. All has been outside of the submitted work. MT has participated in an advisory board for GE Healthcare; and reports speaker’s fee from Echosens, Siemens Healthcare, Tillotts Pharma and Norgine, outside of the submitted work. LV has received a grant and support for travelling and attending meetings from Gilead. He has served as a consultant for Gilead, Pfizer, Astra Zeneca, Novo Nordisk, Intercept pharmaceuticals, Diatech Pharmacogenetics, IONIS, Boehringer Ingelheim and reports being a lecturer or speaker for MSD, Gilead, AlfaSigma, AbbVie, Viatris. In addition, he has participated in advisory boards for Intercept, Pfizer, Gilead, Novo Nordisk. All has been outside of the submitted work. VW-SW served as a consultant or advisory board member for AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Merck, Novo Nordisk, Pfizer, ProSciento, Sagimet Biosciences and TARGET PharmaSolutions; and a speaker for Abbott, AbbVie, Echosens, Gilead Sciences and Novo Nordisk. He has received a grant from Gilead Sciences to support fatty liver research and is a co-founder of Illuminatio Medical Technology Limited, outside of the submitted work. YY has received research grants from Biocodex and Gilead, and is a speaker for Novo Nordisk, Gilead, AbbVie, Abdi İbrahim, Bilim İlaç and Echosens, outside of the submitted work. SMF holds a senior clinical investigator fellowship from the Research Foundation Flanders (FWO) (1802154 N). His institution has received grants from Astellas, Falk Pharma, Genfit, Gilead Sciences, GlympsBio, Janssens Pharmaceutica, Inventiva, Merck Sharp & Dome, Pfizer and Roche. He has acted as consultant for AbbVie, Actelion, Aelin Therapeutics, AgoMab, Aligos Therapeutics, Allergan, Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristoll-Meyers Squibb, CSL Behring, Coherus, Echosens, Eisai, Enyo, Galapagos, Galmed, Genetech, Genfit, Gilead Sciences, Intercept, Inventiva, Janssens Pharmaceutica, Julius Clinical, Madrigal, Medimmune, Merck Sharp & Dome, NGM Bio, Novartis, Novo Nordisk, Promethera and Roche. He has been lecturer for AbbVie, Allergan, Bayer, Eisai, Genfit, Gilead Sciences, Janssens Cilag, Intercept, Inventiva, Merck Sharp & Dome, Novo Nordisk and Promethera, outside of the submitted work. EAT has participated in advisory boards for Intercept, Gilead, Novo-Nordisk and Pfizer, outside of the submitted work. HEM, SAA, and ZMY have nothing to disclose. Please refer to the accompanying ICMJE disclosure forms for further details.