Performance of American Gastroenterological Association Clinical Care Pathway for the risk stratification of patients with nonalcoholic fatty liver disease in the US population
Abstract
Background and aims: The American Gastroenterological Association (AGA) recently launched the Clinical Care Pathway for the Risk Stratification and Management of Patients with NAFLD to identify adults with significant fibrosis. We aimed to examine this pathway’s performance in the US population. Approach and Results: Using the 2017–2018 National Health and Nutrition Examination Survey data, we identified participants aged ≥18 with available Fibrosis‐4 (FIB‐4) score and liver stiffness measurement (LSM) in the absence of other liver diseases. Based on the AGA clinical pathway, FIB‐4 < 1.3 and LSM < 8 kilopascals (kPa) by vibration‐controlled transient elastography (VCTE) are associated with low risk of significant fibrosis. Using these cutoffs, we examined the pathway performance using negative predictive value (NPV) and positive predictive value (PPV) and explored alternative risk‐stratification strategies. There were 2322 participants with available data (projected to 94.2 million US adults). The NPV of LSM ≥ 8 kPa among those with FIB‐4 < 1.3 was 90%, whereas the PPV among those with FIB‐4 1.3–2.67 was 13%. As diabetes was a strong predictor of fibrosis, we propose a simple, alternative strategy to eliminate the indeterminate FIB‐4 range and perform VCTE in those with FIB‐4 ≥ 1.3 and diabetes. This strategy would decrease the number of VCTEs from 14.5 to 4.9 million and increase PPV from 13% to 33% without compromising the NPV among those who did not undergo VCTE. Conclusion: The implementation of the current AGA clinical pathway would lead to overutilization of VCTE. An alternative strategy using FIB‐4 ≥ 1.3 and diabetes to select adults undergoing second‐line testing will improve this pathway’s performance and minimize unnecessary VCTEs.
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Non-invasive modalities being scrutinized include blood tests such as FIB-4, ELF, and Pro-C3/Pro-C5.
“They range from blood tests based on standard lab parameters such as fibrosis-4 (FIB-4) (292, 293), to proprietary tests such as enhanced liver fibrosis test (ELF) (294) and type III collagen propeptide (Pro-C3)/ type V collagen propeptide (Pro-C5) (295).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [292]
Current clinical practice is moving towards multimodality non-invasive diagnostic testing to identify patients at highest risk for advanced fibrosis suitable for trial enrollment or HCC screening.
“Current clinical practice is moving towards the use of multimodality non-invasive diagnostic testing to identify patients at highest risk for advanced fibrosis who may be suitable for either enrollment in a clinical trial or screening for hepatocellular carcinoma (292, 293, 311).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [292]
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Cites
International Diabetes Federation 2017
Carracher, A. M., Marathe, P. H., & Close, K. L. (2018) · Journal of Diabetes · doi:10.1111/1753-0407.12644 · Cited by 13,369 · see citing works
Sterling, R. K., Lissen, E., Clumeck, N., Sola, R., Correa, M. C., Montaner, J., S. Sulkowski, M., Torriani, F. J., Dieterich, D. T., Thomas, D. L., et al. (2006) · Hepatology · doi:10.1002/hep.21178 · Cited by 5,021 · cited 1× · see citing works
“FIB‐4 was developed in a highly selective group of individuals with human immunodeficiency virus and hepatitis C virus coinfection.[7] Therefore, transferring its initial intended use to NAFLD risk‐stratification pathways is fraught with limitations because of several factors.”
BackgroundEASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease
(2016) · Journal of Hepatology · doi:10.1016/j.jhep.2015.11.004 · Cited by 4,836 · see citing works
Chalasani, N., Younossi, Z. M., Lavine, J. E., Diehl, A. M., Brunt, E. M., Cusi, K. J., Charlton, M., & Sanyal, A. J. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.04.001 · Cited by 1,770 · see citing works
ACG clinical guideline: evaluation of abnormal liver chemistries
Kwo, P. Y., Cohen, S. M., & Lim, J. K. (2017) · American Journal of Gastroenterology · doi:10.1038/ajg.2016.517 · Cited by 1,222 · see citing works
Age as a confounding factor for the accurate non-invasive diagnosis of advanced NAFLD fibrosis
McPherson, S., Hardy, T., Dufour, J.-F., Petta, S., Romero-Gomez, M., Allison, M., Oliveira, C. P., Francque, S., Van Gaal, L., Schattenberg, J. M., et al. (2017) · American Journal of Gastroenterology · doi:10.1038/ajg.2016.453 · Cited by 945 · see citing works
Siddiqui, M. S., Vuppalanchi, R., Natta, M. L. V., Hallinan, E., Kowdley, K. V., Abdelmalek, M. F., Neuschwander‐Tetri, B. A., Loomba, R. S., Dasarathy, S., Brandman, D., et al. (2018) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.04.043 · Cited by 618 · see citing works
Kanwal, F., Shubrook, J. H., Adams, L. A., Pfotenhauer, K., Wai-Sun Wong, V., Wright, E., Abdelmalek, M. F., Harrison, S. A., Loomba, R., Mantzoros, C. S., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.07.049 · Cited by 618 · see citing works
Wong, V. W., Chu, C. W., Wong, G. L., Chan, R., Chim, A. M., Ong, A., Yeung, D. K., Yiu, K. K., Chu, S. H.-T., Woo, J., et al. (2011) · Gut · doi:10.1136/gutjnl-2011-300342 · Cited by 491 · see citing works
Kwok, R., Choi, K. C., Wong, G. L., Zhang, Y., Chan, H. L.-Y., Luk, A. O. Y., Shu, S. S., Chan, A. W. H., Yeung, M. W., Chan, J. C. N., et al. (2015) · Gut · doi:10.1136/gutjnl-2015-309265 · Cited by 480 · see citing works
Mózes, F. E., Lee, J. A., Selvaraj, E. A., Jayaswal, A. N. A., Trauner, M., Boursier, J., Fournier, C., Staufer, K., Stauber, R. E., Bugianesi, E., et al. (2022) · Gut · doi:10.1136/gutjnl-2021-324243 · Cited by 477 · see citing works
Low Accuracy of FIB-4 and NAFLD Fibrosis Scores for Screening for Liver Fibrosis in the Population
Graupera, I., Thiele, M. S., Serra‐Burriel, M., Caballería, L., Roulot, D. M., Wong, G. L., Fabrellas, N., Guha, I. N., Arslanow, A., Expósito, C., et al. (2021) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2021.12.034 · Cited by 302 · see citing works
Papatheodoridi, Μ., Hiriart, J., Lupșor‐Platon, M., Bronte, F., Boursier, J., Elshaarawy, O., Marra, F., Thiele, M. S., Markakis, G., Payancé, A., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.11.050 · Cited by 214 · see citing works
American Diabetes Association (2019) · Diabetes Care · doi:10.2337/dc20-s004 · Cited by 207 · see citing works
Bril, F., McPhaul, M. J., Caulfield, M. P., Clark, V., Soldevila‐Pico, C., Firpi-Morell, R. J., Lai, J., Shiffman, D., Rowland, C. M., & Cusi, K. J. (2019) · Diabetes Care · doi:10.2337/dc19-1071 · Cited by 183 · see citing works
Boursier, J., Canivet, C. M., Costentin, C. E., Lannes, A., Delamarre, A., Stürm, N., Bail, B. L., Michalak, S., Oberti, F., Hilleret, M., et al. (2022) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2022.02.059 · Cited by 109 · see citing works
Roulot, D. M., Roudot‐Thoraval, F., Nkontchou, G., Kouacou, N., Costes, J., Elourimi, G., Clésiau, H. L., Ziol, M., & Beaugrand, M. (2017) · Liver International · doi:10.1111/liv.13481 · Cited by 94 · see citing works
Ahmed, O. T., Gidener, T., Mara, K. C., Larson, J. J., Therneau, T. M., & Allen, A. M. (2021) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2021.07.016 · Cited by 94 · see citing works
Self-citationBarbosa, J. V., & Lai, M. (2020) · Hepatology Communications · doi:10.1002/hep4.1618 · Cited by 70 · see citing works
Prospects in non-invasive assessment of liver fibrosis: Liquid biopsy as the future gold standard?
Lambrecht, J., Verhulst, S., Mannaerts, I., Reynaert, H., & van Grunsven, L. A. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.01.009 · Cited by 55 · see citing works
Prevalence and Risk Factors of Advanced Liver Fibrosis in a Population‐Based Study in Germany
Huber, Y., Schulz, A., Schmidtmann, I. M., Beutel, M. E., Pfeiffer, N., Münzel, T. F., Galle, P. R., Wild, P. S., Lackner, K. J., & Schattenberg, J. M. (2022) · Hepatology Communications · doi:10.1002/hep4.1899 · Cited by 46 · see citing works
Congly, S. E., Shaheen, A. A., & Swain, M. G. (2021) · PLoS ONE · doi:10.1371/journal.pone.0251741 · Cited by 36 · see citing works
Foschi, F., Domenicali, M., Giacomoni, P., Dall'aglio, A., Conti, F., Borghi, A., Bevilacqua, V., Napoli, L., Mirici, F., Cucchetti, A., et al. (2020) · Annals of Hepatology · doi:10.1016/j.aohep.2020.04.003 · Cited by 21 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cusi, K. J., Abdelmalek, M. F., Apovian, C. M., Balapattabi, K., Bannuru, R. R., Barb, D., Bardsley, J. K., Beverly, E. A., Corbin, K. D., ElSayed, N. A., et al. (2025) · Diabetes Care · doi:10.2337/dci24-0094 · Cited by 396 · see citing works
Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH)
Wang, S., & Friedman, S. L. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adi0759 · Cited by 158 · see citing works
Noninvasive assessment of liver fibrosis in NAFLD
Sanyal, A. J., Castera, L., & Wong, V. W.-S. (2023) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2023.03.042 · Cited by 157 · see citing works
van Kleef, L. A., Francque, S., Ortíz, J. E. P., Sonneveld, M. J., Sanchez-Luque, C. B., Prieto-Ortiz, R. G., Kwanten, W. J., Vonghia, L., Verrijken, A., Block, C. E. M. D., et al. (2024) · Gastroenterology · doi:10.1053/j.gastro.2024.03.017 · Cited by 85 · see citing works
Implementation of a liver health check in people with type 2 diabetes
Abeysekera, K. W. M., Valenti, L., Younossi, Z., Dillon, J. F., Allen, A. M., Noureddin, M., Rinella, M. E., Tacke, F., Francque, S., Ginès, P., et al. (2024) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(23)00270-4 · Cited by 63 · see citing works
Self-citationZhang, X., Yip, T. C.-F., Wong, G. L.-H., Leow, W.-X., Liang, L. Y., Lim, L.-L., Li, G., Ibrahim, L., Lin, H., Lai, J. C. T., et al. (2023) · Gut · doi:10.1136/gutjnl-2023-330269 · Cited by 55 · see citing works
Tang, M., Liu, M., Zhang, Y., & Xie, R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1160625 · Cited by 52 · see citing works
Pharmaco‐Economic Assessment of Screening Strategies for High‐Risk MASLD in Primary Care
Younossi, Z. M., Paik, J. M., Henry, L. L., Stepanova, M., & Nader, F. (2024) · Liver International · doi:10.1111/liv.16119 · Cited by 45 · see citing works
Ajmera, V. H., Tesfai, K., Sandoval, E., Lopez, S. J., Cervantes, V., Madamba, E. V., Bettencourt, R., Manousou, P., Richards, L., & Loomba, R. S. (2023) · Hepatology · doi:10.1097/hep.0000000000000635 · Cited by 36 · see citing works
Qi, X., Guo, J., Li, Y., Fang, C., Lin, J., Chen, X., & Jia, J. (2024) · Scientific Reports · doi:10.1038/s41598-024-52482-w · Cited by 28 · see citing works
Vidal-Trécan, T., Julla, J., Khoury, T. E., Venteclef, N., Riveline, J., Paradis, V., Valla, D. C., Gautier, J., & Castéra, L. (2025) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2025.02.018 · Cited by 20 · see citing works
Detecting at-risk steatotic liver disease and liver fibrosis in the community
Adams, L. A., Thiele, M. S., & Tsochatzis, E. A. (2025) · Hepatology · doi:10.1097/hep.0000000000001400 · Cited by 14 · see citing works
Lee, H. W., Kim, K. H., Ahn, S. H., Lee, H. C., & Choi, J. (2024) · Liver International · doi:10.1111/liv.15897 · Cited by 14 · see citing works
van Kleef, L. A., Pustjens, J., Schattenberg, J. M., Holleboom, A. G., Cabezas, M. C., Tushuizen, M. E., de Knegt, R. J., Ikram, M. A., Janssen, H. L. A., Francque, S., et al. (2025) · Hepatology · doi:10.1097/hep.0000000000001356 · Cited by 15 · see citing works
Allen, A. M., Lazarus, J. V., Alkhouri, N., Noureddin, M., Wong, V. W., Tsochatzis, E. A., de Avila, L., Racila, A., Nader, F., Mark, H. E., et al. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000678 · Cited by 12 · see citing works
Self-citationPerformance of novel collagen turnover biomarkers to detect increased liver stiffness in MASLD
Hegmar, H., Wiggers, T., Nasr, P., Vessby, J., Kechagias, S., Nyhlin, N., Marschall, H., Borssén, Å. D., Strandberg, R., Karsdal, M. A., et al. (2024) · Journal of Internal Medicine · doi:10.1111/joim.13813 · Cited by 10 · see citing works
Emerging concepts in the detection of liver fibrosis in non-alcoholic fatty liver disease
Armandi, A., Michel, M. S., Gjini, K., Emrich, T., Bugianesi, E., & Schattenberg, J. M. (2023) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2023.2242779 · Cited by 9 · see citing works
Vincentis, A. D., Tavaglione, F., Namba, S., Kanai, M., Okada, Y., Kamatani, Y., Maurotti, S., Pedone, C., Incalzi, R. A., Valenti, L. V. C., et al. (2024) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.17953 · Cited by 9 · see citing works
Diabetes and obesity reduce FIB-4 accuracy in MASLD referral pathways
Shaheen, A., Baguley, E., Swain, M. G., Tam, M., Ma, M. M., Sebastiani, G., Jiang, J., Lee, F. S.-H., Medellin, A., & Abraldeṣ, J. G. (2026) · JHEP Reports · doi:10.1016/j.jhepr.2026.101735 · Cited by 8 · see citing works
Rabbat, J., Yang, B., Lee, H. W., Lin, H., Tsochatzis, E. A., Petta, S., Bugianesi, E., Yoneda, M., Zheng, M., Hagström, H., et al. (2025) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2025.0888 · Cited by 8 · see citing works
Identifying and Linking Patients At Risk for MASLD with Advanced Fibrosis to Care in Primary Care
Xiao, T. G., Witek, L., Bundy, R. A., Moses, A., Obermiller, C. S., Schreiner, A. D., Dharod, A., Russo, M. W., & Rudnick, S. (2024) · Journal of General Internal Medicine · doi:10.1007/s11606-024-08955-9 · Cited by 9 · see citing works
Gheorghe, E. C., Nicolau, C. D., Kamal, A. M., Udriștoiu, Ș., Gruionu, L., & Săftoiu, A. (2023) · Applied Sciences · doi:10.3390/app13085080 · Cited by 8 · see citing works
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Stasi, C., & Mega, A. (2025) · Life · doi:10.3390/life15111682 · Cited by 5 · see citing works
Clayton, M. W., Benson, J. T., Bobek, O. J., Canning, R. E., Ou, F., & Allen, A. M. (2026) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000004080 · Cited by 5 · see citing works
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Urias, E., & Chen, V. L. (2023) · Seminars in Liver Disease · doi:10.1055/a-2082-5203 · Cited by 5 · see citing works
Woodard, J. S., & Abrams, G. A. (2024) · Journal of Endocrinology and Metabolism · doi:10.14740/jem935 · Cited by 4 · see citing works
Ananchaisarp, T., Chamroonkiadtikun, P., Bunchote, K., Thedpun, J., Srisamoot, C., Rujiworanat, C., Jayasakul, V., Chaiphom, N., Kittivarapong, T., Chuaysong, N., et al. (2025) · BMC Family Practice · doi:10.1186/s12875-025-03039-x · Cited by 4 · see citing works
Pustjens, J., Brouwer, W. P., Ayada, I., Janssen, H. L. A., & van Kleef, L. A. (2025) · World Journal of Gastroenterology · doi:10.3748/wjg.v31.i37.107665 · Cited by 4 · see citing works
Managing Nonalcoholic Fatty Liver Disease Through Structured Lifestyle Modification Interventions
Thomas, A., & Thomas, A. (2025) · American Journal of Lifestyle Medicine · doi:10.1177/15598276251346717 · Cited by 6 · see citing works
Bangaru, S. D., Sundaresh, R., Lee, A. H., Prause, N., Hao, F., Dong, T. S., Tincopa, M. A., Cholankeril, G. T., Rich, N. E., Kawamoto, J. K., et al. (2023) · Digestive Diseases and Sciences · doi:10.1007/s10620-023-08043-8 · Cited by 2 · see citing works
Cusi, K. J., Abdelmalek, M. F., Apovian, C. M., Balapattabi, K., Bannuru, R. R., Barb, D., Bardsley, J. K., Beverly, E. A., Corbin, K. D., ElSayed, N. A., et al. (2025) · doi:10.2337/figshare.28673327 · Cited by 2 · see citing works
Ishiba, H., Sumida, Y., Kamada, Y., Fujii, H., Iwaki, M., Hayashi, H., Toyoda, H., Oeda, S., Hyogo, H., Kawanaka, M., et al. (2025) · Gastro Hep Advances · doi:10.1016/j.gastha.2025.100668 · Cited by 1 · see citing works
Kushner, T., Meislin, R., Katzenstein, C., Lange, M., Rodriguez, N., Rosberger, S., Rios, J., Alpert, L., Argiriadi, P. A., Worthington, T., et al. (2026) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2026.04.011 · Cited by 1 · see citing works
Dounel, J., Díaz, L. A., Bettencourt, R., Tavaglione, F., Madamba, E. V., Richards, L., Loomba, R. S., & Ajmera, V. H. (2026) · Gastro Hep Advances · doi:10.1016/j.gastha.2026.101022 · Cited by 1 · see citing works
Disease-specific non-invasive assessment of liver fibrosis and portal hypertension
Cavoli, T. V. L., Curto, A., Lynch, E. N., Galli, A., & Milani, S. (2025) · Minerva Gastroenterology · doi:10.23736/s2724-5985.25.03845-8 · Cited by 1 · see citing works
Sun, C., Li, R., Shen, C., Zeng, Y., Li, J., Zhang, Q., Xue, H., Li, L., Yu, C.-C., Chen, X., et al. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.5048711
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Yuan, Y., Wang, S., Ding, J., Jiang, J., Zeng, Y., Li, T., Shinohara, A. K., Lin, C., Sun, C., Hoogeveen, R. C., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.19.726408
- Authors
- Udompap, P., Therneau, T. M., Canning, R. E., Benson, J. T., & Allen, A. M.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Allen, Alina M.
- Venue
- Hepatology
- Published
- 2023-02-17
- Volume
- 77
- Issue
- 3
- Pages
- 931-941
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W4292560094
- Cited by
- 37
- References
- 23
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 9 · 2023: 10
- FWCI
- 5.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R03DK128127, K23DK115594)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Keywords
- non-alcoholic fatty liver disease, liver fibrosis, risk stratification, Fibrosis-4 score, vibration-controlled transient elastography, liver stiffness measurement, diabetes mellitus, predictive value
- MeSH terms
- Adult, Biopsy, Diabetes Mellitus, Fibrosis, Humans, Liver, Liver Cirrhosis, Nutrition Surveys, Prospective Studies, Severity of Illness Index, United States, Risk Assessment, Critical Pathways, Elasticity Imaging Techniques, Non-alcoholic Fatty Liver Disease
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