Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis

Zobair M. Younossi; Rohit Loomba; Quentin M. Anstee; Mary E. Rinella; Elisabetta Bugianesi; Giulio Marchesini; Brent A. Neuschwander-Tetri; Lawrence Serfaty; Francesco Negro; Stephen H. Caldwell; Vlad Ratziu; Kathleen E. Corey; Scott L. Friedman; Manal F. Abdelmalek; Stephen A. Harrison; Arun J. Sanyal; Joel E. Lavine; Philippe Mathurin; Michael R. Charlton; Zachary D. Goodman; Naga P. Chalasani; Kris V. Kowdley; Jacob George; Keith Lindor

doi:10.1002/hep.29721

Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis

Zobair M. Younossi, Rohit Loomba, Quentin M. Anstee, Mary E. Rinella, Elisabetta Bugianesi, Giulio Marchesini, Brent A. Neuschwander-Tetri, Lawrence Serfaty, Francesco Negro, Stephen H. Caldwell, Vlad Ratziu, Kathleen E. Corey, Scott L. Friedman, Manal F. Abdelmalek, Stephen A. Harrison, Arun J. Sanyal, Joel E. Lavine, Philippe Mathurin, Michael R. Charlton, Zachary D. GoodmanNaga P. Chalasani, Kris V. Kowdley, Jacob George, Keith Lindor

Research output: Contribution to journal › Review article › peer-review

244 Scopus citations

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a spectrum comprised of isolated steatosis, nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. The majority of NAFLD subjects do not have NASH and do not carry a significant risk for liver-related adverse outcomes (cirrhosis and mortality). Globally, the prevalence of NAFLD is approximately 25%. In Asia, a gradient of high to low prevalence rates is noted from urban to rural areas. Given the prevalence of NAFLD, the clinical and economic burden of NAFLD and NASH can be substantial. With increasing recognition of NASH as an important liver disease, the diagnosis of NASH still requires a liver biopsy that is suboptimal. Although liver biopsy is the most accurate modality to diagnose and stage the severity of NASH, this method suffers from being invasive, costly, associated with potential complications, and plagued with interobserver variability of individual pathological features. A number of noninvasive modalities to diagnose NASH and stage liver fibrosis are being developed. These modalities include predictive models (NAFLD fibrosis score) and serum biomarkers such as enhanced liver fibrosis (ELF). Other tests are based on radiological techniques, such as transient elastography (TE) or magnetic resonance elastography (MRE), which are used to estimate liver stiffness as a potential surrogate of hepatic fibrosis. Although a dynamic field of research, most of these diagnostic modalities have area under the curve ranging between 0.76 and 0.90%, with MRE having the best predictive performance. In summary, developing safe and easily accessible noninvasive modalities to accurately diagnose and monitor NASH and associated fibrosis is of utmost importance in clinical practice and clinical research. These tests are not only important to risk stratify subjects at the greatest risk for progressive liver disease, but also to serve as appropriate surrogate endpoints for therapeutic clinical trials of NASH. (Hepatology 2018;68:349-360).

Original language	English (US)
Pages (from-to)	349-360
Number of pages	12
Journal	Hepatology
Volume	68
Issue number	1
DOIs	https://doi.org/10.1002/hep.29721
State	Published - Jul 2018

ASJC Scopus subject areas

Hepatology

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10.1002/hep.29721

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Younossi, Z. M., Loomba, R., Anstee, Q. M., Rinella, M. E., Bugianesi, E., Marchesini, G., Neuschwander-Tetri, B. A., Serfaty, L., Negro, F., Caldwell, S. H., Ratziu, V., Corey, K. E., Friedman, S. L., Abdelmalek, M. F., Harrison, S. A., Sanyal, A. J., Lavine, J. E., Mathurin, P., Charlton, M. R., ... Lindor, K. (2018). Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis. Hepatology, 68(1), 349-360. https://doi.org/10.1002/hep.29721

Younossi, ZM, Loomba, R, Anstee, QM, Rinella, ME, Bugianesi, E, Marchesini, G, Neuschwander-Tetri, BA, Serfaty, L, Negro, F, Caldwell, SH, Ratziu, V, Corey, KE, Friedman, SL, Abdelmalek, MF, Harrison, SA, Sanyal, AJ, Lavine, JE, Mathurin, P, Charlton, MR, Goodman, ZD, Chalasani, NP, Kowdley, KV, George, J & Lindor, K 2018, 'Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis', Hepatology, vol. 68, no. 1, pp. 349-360. https://doi.org/10.1002/hep.29721

@article{147caaefb7bb4ef4a1ddf3fba42472e4,

title = "Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis",

abstract = "Nonalcoholic fatty liver disease (NAFLD) is a spectrum comprised of isolated steatosis, nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. The majority of NAFLD subjects do not have NASH and do not carry a significant risk for liver-related adverse outcomes (cirrhosis and mortality). Globally, the prevalence of NAFLD is approximately 25%. In Asia, a gradient of high to low prevalence rates is noted from urban to rural areas. Given the prevalence of NAFLD, the clinical and economic burden of NAFLD and NASH can be substantial. With increasing recognition of NASH as an important liver disease, the diagnosis of NASH still requires a liver biopsy that is suboptimal. Although liver biopsy is the most accurate modality to diagnose and stage the severity of NASH, this method suffers from being invasive, costly, associated with potential complications, and plagued with interobserver variability of individual pathological features. A number of noninvasive modalities to diagnose NASH and stage liver fibrosis are being developed. These modalities include predictive models (NAFLD fibrosis score) and serum biomarkers such as enhanced liver fibrosis (ELF). Other tests are based on radiological techniques, such as transient elastography (TE) or magnetic resonance elastography (MRE), which are used to estimate liver stiffness as a potential surrogate of hepatic fibrosis. Although a dynamic field of research, most of these diagnostic modalities have area under the curve ranging between 0.76 and 0.90%, with MRE having the best predictive performance. In summary, developing safe and easily accessible noninvasive modalities to accurately diagnose and monitor NASH and associated fibrosis is of utmost importance in clinical practice and clinical research. These tests are not only important to risk stratify subjects at the greatest risk for progressive liver disease, but also to serve as appropriate surrogate endpoints for therapeutic clinical trials of NASH. (Hepatology 2018;68:349-360).",

author = "Younossi, {Zobair M.} and Rohit Loomba and Anstee, {Quentin M.} and Rinella, {Mary E.} and Elisabetta Bugianesi and Giulio Marchesini and Neuschwander-Tetri, {Brent A.} and Lawrence Serfaty and Francesco Negro and Caldwell, {Stephen H.} and Vlad Ratziu and Corey, {Kathleen E.} and Friedman, {Scott L.} and Abdelmalek, {Manal F.} and Harrison, {Stephen A.} and Sanyal, {Arun J.} and Lavine, {Joel E.} and Philippe Mathurin and Charlton, {Michael R.} and Goodman, {Zachary D.} and Chalasani, {Naga P.} and Kowdley, {Kris V.} and Jacob George and Keith Lindor",

note = "Funding Information: Copyright VC 2017 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.29721 Potential conflict of interest: Dr. Younossi consults for Bristol-Myers Squibb, Novo Nordisk, Novartis, Intercept, Gilead, Allergan, and GlaxoSmithKline. He advises for Bistol Myers Squib and Novartis. Dr. Charlton consults for and received grants from Gilead, Intercept, NGM, Genfit, and Novartis. He received grants from Conatus. Dr. Abdelmalek received grants from Promethus and Metabolon. Dr. Kowdley consults for, advises for, is on the speakers{\textquoteright} bureau for, and received grants from Gilead and Intercept. He advises for and received grants from Allergan. He consults for Verlyx. He advises for Conatus. He received grants from Galectin, Immuron, NGM, Prometheus, and Zydus. Dr. Goodman consults for and received grants from Allergan. He consults for Pfizer. He received grants from Gilead, Galectin, Conatus, Exalenz, Intercept, Sanofi, Novartis, and Bristol-Myers Squibb. Dr. Ratziu consults for and received grants from Intercept. He consults for Galmed, Genfit, Boehringer Ingelhim, Pfizer, and Allergan. He received grants from Gilead. Dr. Anstee consults for, is on the speakers{\textquoteright} bureau for, and received grants from Allergan/Tobira and Genfit. He consults for and is on the speakers{\textquoteright} bureau for Abbott. He consults for and received grants from Eli Lilly, Intercept, Novartis, and Pfizer. He consults for Acuitas, E3Bio, Galmed, Gilead, Grunthal, Imperial Innoations, Inventiva, Janssen, Kenes, MedImmune, NewGene, and Raptor. He is on the speakers{\textquoteright} bureau for Clinical Care Options. He received grants from AbbVie, Antaros, AstraZeneca, Boehringer Ingelheim, Ellegaard Gottigen, Exalenz, GlaxoSmithKline, Vertex, iXscient, Nordic Bioscience, Novo Nordisk, One Way Liver Genomics, Perspectum, Sanofi-Aventis, SomaLogic, and Takeda. Dr. Harrison consults for and owns stock in Cirius and Madrigal. He consults for Cymetrix, Novartis, Perspectum, Intercept, Novo Nordisk, Capulus, CiVi, NGM, CLDF, Genfit, Echosens, High Index, and Prometheus. He advises for Gilead. He is on the speakers{\textquoteright} bureau for Alexion. Dr. Tetri consults for and advises Nimbus, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Enanta, Novartis, Galmed, Zafgen, Receptos, Pfizer, Allergan, MedImmue/AstraZeneca, ConSynance, Tobira, Karos, Afimmune, NuSirt, Arrowhead, Reset, Intercept, Gilead, Abide, and Cymabay. Dr. Friedman consults for, has research contracts with, and owns stock in Scholar Rock. He consults for and has research contracts with Bristol-Myers Squibb, Enanta, and Zafgen. He consults for and owns stock in Exalenz, Blade, DeuteRx, Galectin, Genfit, Glympse, Jecure, Lifemax, and Northern Biologics. He consults for Abide, Affimune, Allegan, Angion, Arubutus, Arrowheard, Avaliv, Axcella, Boehringer Ingelheim, Can-Fite, ChemomAb, Contravir, CymaBay, Five Prime, Fortress, Gemphire, Glycotest, Inception, Lexicon, Metacrine, Metagenix, Morphic Rock, Nitto, Novartis, Ocera, Perspectum, Pfizer, Revive, RiverVest, Roche/Genentech, Sandhill, Second Genome, Surrozen, Takeda, Teva, Third Rock, Tokai, Viking, Vivace, VL-45, X-Tuit, and Zydus. He has research contracts with AbbVie and 3V Bio. He owns stock in Akarna, BirdRock, Conatus, Intercept, Nimbus, and Tobira. Dr. Mathurin consults for and is on the speakers{\textquoteright} bureau for Gilead. He consults for Sanofi and Verlyx. Dr. Marchesini advises for and received grants from Gilead and Eli Lilly. He received grants from Novo Nordisk, Genfit, and Janssen. Dr. Negro consults for and received grants from Gilead and AbbVie. He consults for Merck. Dr. Rinella consults for Intercept, Gilead, Immuron, NGM, Nusirt, Enanta, and Novartis. Dr. Caldwell consults for Shionogi and Gencia. He received grants from Gilead, Genfit, Galmed, NGM, Immuron, Conatus, Vital Therapy, Target, and TaiwanJ. Dr. Chalansani consults for and received grants from Lilly. He consults for AbbVie, Nusirt, Tobira/Allergan, Affimune, Axovant, Immuron, Ardelyx, and Madrigal. He received grants from Gilead, Galectin, and Cumberland. Dr. Sanyal consults for and received grants from Gilead, Malinckrodt, and Salix. He consults for and is employed by Sanyal Bio. He consults for Pfizer, Nimbus, Nitto Denko, Hemoshear, and Lilly. He received grants from Conatus, Novartis, Galectin, Bristol-Myers Squibb, Merck, and Sequana. He received royalties from Elsevier and Uptodate. He owns stock in Akarna, GenFit, and NewCo. Publisher Copyright: {\textcopyright} 2017 by the American Association for the Study of Liver Diseases.",

year = "2018",

month = jul,

doi = "10.1002/hep.29721",

language = "English (US)",

volume = "68",

pages = "349--360",

journal = "Hepatology",

issn = "0270-9139",

publisher = "John Wiley and Sons Ltd",

number = "1",

}

TY - JOUR

T1 - Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis

AU - Younossi, Zobair M.

AU - Loomba, Rohit

AU - Anstee, Quentin M.

AU - Rinella, Mary E.

AU - Bugianesi, Elisabetta

AU - Marchesini, Giulio

AU - Neuschwander-Tetri, Brent A.

AU - Serfaty, Lawrence

AU - Negro, Francesco

AU - Caldwell, Stephen H.

AU - Ratziu, Vlad

AU - Corey, Kathleen E.

AU - Friedman, Scott L.

AU - Abdelmalek, Manal F.

AU - Harrison, Stephen A.

AU - Sanyal, Arun J.

AU - Lavine, Joel E.

AU - Mathurin, Philippe

AU - Charlton, Michael R.

AU - Goodman, Zachary D.

AU - Chalasani, Naga P.

AU - Kowdley, Kris V.

AU - George, Jacob

AU - Lindor, Keith

N1 - Funding Information: Copyright VC 2017 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.29721 Potential conflict of interest: Dr. Younossi consults for Bristol-Myers Squibb, Novo Nordisk, Novartis, Intercept, Gilead, Allergan, and GlaxoSmithKline. He advises for Bistol Myers Squib and Novartis. Dr. Charlton consults for and received grants from Gilead, Intercept, NGM, Genfit, and Novartis. He received grants from Conatus. Dr. Abdelmalek received grants from Promethus and Metabolon. Dr. Kowdley consults for, advises for, is on the speakers’ bureau for, and received grants from Gilead and Intercept. He advises for and received grants from Allergan. He consults for Verlyx. He advises for Conatus. He received grants from Galectin, Immuron, NGM, Prometheus, and Zydus. Dr. Goodman consults for and received grants from Allergan. He consults for Pfizer. He received grants from Gilead, Galectin, Conatus, Exalenz, Intercept, Sanofi, Novartis, and Bristol-Myers Squibb. Dr. Ratziu consults for and received grants from Intercept. He consults for Galmed, Genfit, Boehringer Ingelhim, Pfizer, and Allergan. He received grants from Gilead. Dr. Anstee consults for, is on the speakers’ bureau for, and received grants from Allergan/Tobira and Genfit. He consults for and is on the speakers’ bureau for Abbott. He consults for and received grants from Eli Lilly, Intercept, Novartis, and Pfizer. He consults for Acuitas, E3Bio, Galmed, Gilead, Grunthal, Imperial Innoations, Inventiva, Janssen, Kenes, MedImmune, NewGene, and Raptor. He is on the speakers’ bureau for Clinical Care Options. He received grants from AbbVie, Antaros, AstraZeneca, Boehringer Ingelheim, Ellegaard Gottigen, Exalenz, GlaxoSmithKline, Vertex, iXscient, Nordic Bioscience, Novo Nordisk, One Way Liver Genomics, Perspectum, Sanofi-Aventis, SomaLogic, and Takeda. Dr. Harrison consults for and owns stock in Cirius and Madrigal. He consults for Cymetrix, Novartis, Perspectum, Intercept, Novo Nordisk, Capulus, CiVi, NGM, CLDF, Genfit, Echosens, High Index, and Prometheus. He advises for Gilead. He is on the speakers’ bureau for Alexion. Dr. Tetri consults for and advises Nimbus, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Enanta, Novartis, Galmed, Zafgen, Receptos, Pfizer, Allergan, MedImmue/AstraZeneca, ConSynance, Tobira, Karos, Afimmune, NuSirt, Arrowhead, Reset, Intercept, Gilead, Abide, and Cymabay. Dr. Friedman consults for, has research contracts with, and owns stock in Scholar Rock. He consults for and has research contracts with Bristol-Myers Squibb, Enanta, and Zafgen. He consults for and owns stock in Exalenz, Blade, DeuteRx, Galectin, Genfit, Glympse, Jecure, Lifemax, and Northern Biologics. He consults for Abide, Affimune, Allegan, Angion, Arubutus, Arrowheard, Avaliv, Axcella, Boehringer Ingelheim, Can-Fite, ChemomAb, Contravir, CymaBay, Five Prime, Fortress, Gemphire, Glycotest, Inception, Lexicon, Metacrine, Metagenix, Morphic Rock, Nitto, Novartis, Ocera, Perspectum, Pfizer, Revive, RiverVest, Roche/Genentech, Sandhill, Second Genome, Surrozen, Takeda, Teva, Third Rock, Tokai, Viking, Vivace, VL-45, X-Tuit, and Zydus. He has research contracts with AbbVie and 3V Bio. He owns stock in Akarna, BirdRock, Conatus, Intercept, Nimbus, and Tobira. Dr. Mathurin consults for and is on the speakers’ bureau for Gilead. He consults for Sanofi and Verlyx. Dr. Marchesini advises for and received grants from Gilead and Eli Lilly. He received grants from Novo Nordisk, Genfit, and Janssen. Dr. Negro consults for and received grants from Gilead and AbbVie. He consults for Merck. Dr. Rinella consults for Intercept, Gilead, Immuron, NGM, Nusirt, Enanta, and Novartis. Dr. Caldwell consults for Shionogi and Gencia. He received grants from Gilead, Genfit, Galmed, NGM, Immuron, Conatus, Vital Therapy, Target, and TaiwanJ. Dr. Chalansani consults for and received grants from Lilly. He consults for AbbVie, Nusirt, Tobira/Allergan, Affimune, Axovant, Immuron, Ardelyx, and Madrigal. He received grants from Gilead, Galectin, and Cumberland. Dr. Sanyal consults for and received grants from Gilead, Malinckrodt, and Salix. He consults for and is employed by Sanyal Bio. He consults for Pfizer, Nimbus, Nitto Denko, Hemoshear, and Lilly. He received grants from Conatus, Novartis, Galectin, Bristol-Myers Squibb, Merck, and Sequana. He received royalties from Elsevier and Uptodate. He owns stock in Akarna, GenFit, and NewCo. Publisher Copyright: © 2017 by the American Association for the Study of Liver Diseases.

PY - 2018/7

Y1 - 2018/7

N2 - Nonalcoholic fatty liver disease (NAFLD) is a spectrum comprised of isolated steatosis, nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. The majority of NAFLD subjects do not have NASH and do not carry a significant risk for liver-related adverse outcomes (cirrhosis and mortality). Globally, the prevalence of NAFLD is approximately 25%. In Asia, a gradient of high to low prevalence rates is noted from urban to rural areas. Given the prevalence of NAFLD, the clinical and economic burden of NAFLD and NASH can be substantial. With increasing recognition of NASH as an important liver disease, the diagnosis of NASH still requires a liver biopsy that is suboptimal. Although liver biopsy is the most accurate modality to diagnose and stage the severity of NASH, this method suffers from being invasive, costly, associated with potential complications, and plagued with interobserver variability of individual pathological features. A number of noninvasive modalities to diagnose NASH and stage liver fibrosis are being developed. These modalities include predictive models (NAFLD fibrosis score) and serum biomarkers such as enhanced liver fibrosis (ELF). Other tests are based on radiological techniques, such as transient elastography (TE) or magnetic resonance elastography (MRE), which are used to estimate liver stiffness as a potential surrogate of hepatic fibrosis. Although a dynamic field of research, most of these diagnostic modalities have area under the curve ranging between 0.76 and 0.90%, with MRE having the best predictive performance. In summary, developing safe and easily accessible noninvasive modalities to accurately diagnose and monitor NASH and associated fibrosis is of utmost importance in clinical practice and clinical research. These tests are not only important to risk stratify subjects at the greatest risk for progressive liver disease, but also to serve as appropriate surrogate endpoints for therapeutic clinical trials of NASH. (Hepatology 2018;68:349-360).

AB - Nonalcoholic fatty liver disease (NAFLD) is a spectrum comprised of isolated steatosis, nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. The majority of NAFLD subjects do not have NASH and do not carry a significant risk for liver-related adverse outcomes (cirrhosis and mortality). Globally, the prevalence of NAFLD is approximately 25%. In Asia, a gradient of high to low prevalence rates is noted from urban to rural areas. Given the prevalence of NAFLD, the clinical and economic burden of NAFLD and NASH can be substantial. With increasing recognition of NASH as an important liver disease, the diagnosis of NASH still requires a liver biopsy that is suboptimal. Although liver biopsy is the most accurate modality to diagnose and stage the severity of NASH, this method suffers from being invasive, costly, associated with potential complications, and plagued with interobserver variability of individual pathological features. A number of noninvasive modalities to diagnose NASH and stage liver fibrosis are being developed. These modalities include predictive models (NAFLD fibrosis score) and serum biomarkers such as enhanced liver fibrosis (ELF). Other tests are based on radiological techniques, such as transient elastography (TE) or magnetic resonance elastography (MRE), which are used to estimate liver stiffness as a potential surrogate of hepatic fibrosis. Although a dynamic field of research, most of these diagnostic modalities have area under the curve ranging between 0.76 and 0.90%, with MRE having the best predictive performance. In summary, developing safe and easily accessible noninvasive modalities to accurately diagnose and monitor NASH and associated fibrosis is of utmost importance in clinical practice and clinical research. These tests are not only important to risk stratify subjects at the greatest risk for progressive liver disease, but also to serve as appropriate surrogate endpoints for therapeutic clinical trials of NASH. (Hepatology 2018;68:349-360).

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UR - http://www.scopus.com/inward/citedby.url?scp=85045842086&partnerID=8YFLogxK

U2 - 10.1002/hep.29721

DO - 10.1002/hep.29721

M3 - Review article

C2 - 29222917

AN - SCOPUS:85045842086

SN - 0270-9139

VL - 68

SP - 349

EP - 360

JO - Hepatology

JF - Hepatology

IS - 1

ER -

Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis

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