TY - JOUR
T1 - Diagnostic accuracy of elastography and magnetic resonance imaging in patients with NAFLD: A systematic review and meta-analysis
AU - LITMUS Investigators
AU - Selvaraj, Emmanuel Anandraj
AU - Mózes, Ferenc Emil
AU - Jayaswal, Arjun Narayan Ajmer
AU - Zafarmand, Mohammad Hadi
AU - Vali, Yasaman
AU - Lee, Jenny A.
AU - Levick, Christina Kim
AU - Young, Liam Arnold Joseph
AU - Palaniyappan, Naaventhan
AU - Liu, Chang-Hai
AU - Aithal, Guruprasad Padur
AU - Romero-Gómez, Manuel
AU - Brosnan, M. Julia
AU - Tuthill, Theresa A.
AU - Anstee, Quentin M.
AU - Neubauer, Stefan
AU - Harrison, Stephen A.
AU - Bossuyt, Patrick M.
AU - Pavlides, Michael
AU - Anstee, Quentin
AU - Daly, Ann
AU - Johnson, Katherine
AU - Govaere, Olivier
AU - Cockell, Simon
AU - Tiniakos, Dina
AU - Bedossa, Pierre
AU - Oakley, Fiona
AU - Cordell, Heather
AU - Day, Chris
AU - Wonders, Kristy
AU - Bossuyt, Patrick
AU - Zafarmand, Hadi
AU - Lee, Jenny
AU - Ratziu, Vlad
AU - Clement, Karine
AU - Pais, Raluca
AU - Schuppan, Detlef
AU - Schattenberg, J. rn
AU - Vidal-Puig, Toni
AU - Vacca, Michele
AU - Rodrigues-Cuenca, Sergio
AU - Allison, Mike
AU - Kamzolas, Ioannis
AU - Petsalaki, Evangelia
AU - Oresic, Matej
AU - Hyötyläinen, Tuulia
AU - McGlinchey, Aiden
AU - Mato, Jose M.
AU - Millet, Oscar
AU - van Mil, Saskia
N1 - Funding Information: EAS, FEM, MHZ, YV, JAL, CKL, LAJY, NP, CHL, GPA and PMB have nothing to declare. ANAJ, SN and MP are shareholders of Perspectum Ltd. MRG reports grant funding from Gilead Sciences and Intercept; consultancy from Allergan, Gilead Science, Intercept, Medimmune, Shionogi, ProSciento, Kaleido, Siemens, Abbvie, Novo Nordisk, Genfit and Zydus. MJB and TAT are shareholders and employees of Pfizer. QMA is coordinator of the IMI2 LITMUS consortium and he reports research grant funding from Abbvie, Allergan/Tobira, AstraZeneca, GlaxoSmithKline, Glympse Bio, Novartis Pharma AG, Pfizer Ltd., Vertex; consultancy on behalf of Newcastle University for Abbott Laboratories, Acuitas Medical, Allergan/Tobira, Blade, BNN Cardio, Cirius, CymaBay, EcoR1, E3Bio, Eli Lilly & Company Ltd., Galmed, Genfit SA, Gilead, Grunthal, HistoIndex, Indalo, Imperial Innovations, Intercept Pharma Europe Ltd., Inventiva, IQVIA, Janssen, Kenes, Madrigal, MedImmune, Metacrine, NewGene, NGMBio, North Sea Therapeutics, Novartis, Novo Nordisk A/S, Pfizer Ltd., Poxel, ProSciento, Raptor Pharma, Servier, Viking Therapeutics; and speaker fees from Abbott Laboratories, Allergan/Tobira, BMS, Clinical Care Options, Falk, Fishawack, Genfit SA, Gilead, Integritas Communications, MedScape. SAH has research grants from Akero, Axcella, Cirius, CiVi Biopharma, Cymabay, Galectin, Galmed, Genfit, Gilead Sciences, Hepion Pharmaceuticals, Hightide Therapeutics, Intercept, Madrigal, Metacrine, NGM Bio, Northsea Therapeutics, Novartis, Novo Nordisk, Poxel, Sagimet, Viking. He has received consulting fees from Akero, Altimmune, Alentis, Arrowhead, Axcella, Canfite, Cirius, CiVi, Cymabay, Echosens, Enyo, Fibronostics, Foresite Labs, Fortress Biotech, Galectin, Genfit, Gilead Sciences, Hepion, HIghtide, HistoIndex, Intercept, Kowa, Madrigal, Metacrine, NGM, Northsea, Novartis, Novo Nordisk, Poxel, Prometic, Ridgeline, Sagimet, Terns, and Viking. Funding Information: This work has been undertaken as part of the LITMUS (Liver Investigation: Testing Marker Utility in Steatohepatitis) project. The LITMUS project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 777377. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and Europen Federation of Pharmaceutical Industries and Associations (efpia.eu). Funding Information: This work has been undertaken as part of the LITMUS (Liver Investigation: Testing Marker Utility in Steatohepatitis) project. The LITMUS project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 777377. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and Europen Federation of Pharmaceutical Industries and Associations ( efpia.eu ). Publisher Copyright: © 2021 The Author(s)
PY - 2021/10/1
Y1 - 2021/10/1
N2 - Background and Aims: Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) have been proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH). Methods: PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests, against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model. Results: We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and 4 2DSWE studies, and for diagnosing NASH in 4 MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs. Conclusions: When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking. Lay summary: Non-invasive tests that measure liver stiffness or use magnetic resonance imaging (MRI) have been suggested as alternatives to liver biopsy for assessing the severity of liver scarring (fibrosis) and fatty inflammation (steatohepatitis) in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we summarise the results of previously published studies on how accurately these non-invasive tests can diagnose liver fibrosis and inflammation, using liver biopsy as the reference. We found that some techniques that measure liver stiffness had a good performance for the diagnosis of severe liver scarring.
AB - Background and Aims: Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) have been proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH). Methods: PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests, against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model. Results: We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and 4 2DSWE studies, and for diagnosing NASH in 4 MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs. Conclusions: When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking. Lay summary: Non-invasive tests that measure liver stiffness or use magnetic resonance imaging (MRI) have been suggested as alternatives to liver biopsy for assessing the severity of liver scarring (fibrosis) and fatty inflammation (steatohepatitis) in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we summarise the results of previously published studies on how accurately these non-invasive tests can diagnose liver fibrosis and inflammation, using liver biopsy as the reference. We found that some techniques that measure liver stiffness had a good performance for the diagnosis of severe liver scarring.
KW - Biomarkers
KW - Diffusion-weighted imaging
KW - Iron-corrected T1
KW - Liver fibrosis
KW - Magnetic resonance elastography
KW - NASH-MRI
KW - Non-alcoholic fatty liver disease
KW - Non-alcoholic steatohepatitis
KW - Shear wave elastography
KW - Transient elastography
KW - deMILI
KW - fibro-MRI
UR - http://www.scopus.com/inward/record.url?scp=85108940286&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jhep.2021.04.044
DO - https://doi.org/10.1016/j.jhep.2021.04.044
M3 - Article
C2 - 33991635
SN - 0168-8278
VL - 75
SP - 770
EP - 785
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 4
ER -