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AGA Clinical Practice Update on the Role of Noninvasive Biomarkers in the Evaluation and Management of Nonalcoholic Fatty Liver Disease: Expert Review

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Wattacheril, Julia J., Abdelmalek, Manal F., Lim, Joseph K., Sanyal, Arun J.·2023·Gastroenterology

DOI 10.1053/j.gastro.2023.06.013

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Abstract

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review is to provide clinicians with guidance on the use of noninvasive tests (NITs) in the evaluation and management of patients with nonalcoholic fatty liver disease (NAFLD). NAFLD affects nearly 30% of the global population and is a growing cause of end-stage liver disease and liver-related health care resource utilization. However, only a minority of all patients with NAFLD experience a liver-related outcome. It is therefore critically important for clinicians to assess prognosis and identify those with increased risk of disease progression and negative clinical outcomes at the time of initial assessment. It is equally important to assess disease trajectory over time, particularly in response to currently available therapeutic approaches. The reference standard for assessment of prognosis and disease monitoring is histologic examination of liver biopsy specimens. There are, however, many limitations of liver biopsies and their reading that have limited their use in routine practice. The utilization of NITs facilitates risk stratification of patients and longitudinal assessment of disease progression for patients with NAFLD. This clinical update provides best practice advice based on a review of the literature on the utilization of NITs in the management of NAFLD for clinicians. Accordingly, a combination of available evidence and consensus-based expert opinion, without formal rating of the strength and quality of the evidence, was used to develop these best practice advice statements. METHODS: This Expert Review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. These best practice advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these best practice advice statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: NITs can be used for risk stratification in the diagnostic evaluation of patients with NAFLD. BEST PRACTICE ADVICE 2: A Fibrosis 4 Index score <1.3 is associated with strong negative predictive value for advanced hepatic fibrosis and may be useful for exclusion of advanced hepatic fibrosis in patients with NAFLD. BEST PRACTICE ADVICE 3: A combination of 2 or more NITs combining serum biomarkers and/or imaging-based biomarkers is preferred for staging and risk stratification of patients with NAFLD whose Fibrosis 4 Index score is >1.3. BEST PRACTICE ADVICE 4: Use of NITs in accordance with manufacturer's specifications (eg, not in patients with ascites or pacemakers) can minimize risk of discordant results and adverse events. BEST PRACTICE ADVICE 5: NITs should be interpreted with context and consideration of pertinent clinical data (eg, physical examination, biochemical, radiographic, and endoscopic) to optimize positive predictive value in the identification of patients with advanced fibrosis. BEST PRACTICE ADVICE 6: Liver biopsy should be considered for patients with NIT results that are indeterminate or discordant; conflict with other clinical, laboratory, or radiologic findings; or when alternative etiologies for liver disease are suspected. BEST PRACTICE ADVICE 7: Serial longitudinal monitoring using NITs for assessment of disease progression or regression may inform clinical management (ie, response to lifestyle modification or therapeutic intervention). BEST PRACTICE ADVICE 8: Patients with NAFLD and NITs results suggestive of advanced fibrosis (F3) or cirrhosis (F4) should be considered for surveillance of liver complications (eg, hepatocellular carcinoma screening and variceal screening per Baveno criteria). Patients with NAFLD and NITs suggestive of advanced hepatic fibrosis (F3) or (F4), should be monitored with serial liver stiffness measurement; vibration controlled transient elastography; or magnetic resonance elastography, given its correlation with clinically significant portal hypertension and clinical decompensation.

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Imaging in MASLD
Venkatesh, S. K. (2026) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2026.2636184 · Cited by 3
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Monogenic and Polygenic Risk in Common Liver Diseases: Implications for Clinical Care
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InfluentialSelf-citation
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Performance of three clinical scores for steatosis and steatohepatitis and their interaction with metabolic syndrome in obese individuals
Farina, G. S., Brambilla, B., Pandolfo, E. M., Lazzaretti, L. K. N., Kuiava, S. M. S., Graciolli, A. M., Kriger, V. M., Fistarol, C. H. D. B., Sgarioni, A. C., GIOVANARDI, H. J., et al. (2026) · World Journal of Hepatology · doi:10.4254/wjh.v18.i2.111962 · Cited by 2
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“In patients with low-risk LSM ( ≤ 8.0 kilopas-cals, kPa), VCTE should be repeated every two years, whereas patients with intermediate-(8.1–12.0 kPa) and high-risk LSM (> 12.0 kPa) should be considered for annual VCTE monitoring or liver biopsy if non-invasive tests are discordant [34].”
Influential
Explainable machine learning models predict liver fibrosis risk and outcome in the general population: Development and multi-cohort external validation
Zhu, G., Yi, Q., Xu, R., Xie, Y., Song, Y.-P., Wang, X.-C., Huang, L., & Xiang, Y. (2026) · Comput. Methods Programs Biomed. · doi:10.1016/j.cmpb.2026.109533 · Cited by 1
The role of primary care in response to the global liver disease syndemic: a Lancet Gastroenterology & Hepatology Commission
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Woodard, J. S., Velji-Ibrahim, J., Alden, J., & Abrams, G. A. (2024) · Case Reports in Gastrointestinal Medicine · doi:10.1155/2024/7938701 · Cited by 2
“Terefore, screening for liver fbrosis in MASLD has moved away from obtaining a liver biopsy, and the recent AGA guidelines recommend screening with noninvasive testing that include VCTE, the enhanced liver fbrosis (ELF) test, or magnetic resonance elastography (MRE) [2].”
Background
Predictors of Significant Fibrosis Among People Living with HIV with Metabolic Dysfunction- Associated Steatotic Liver Disease
Prasoppokakorn, T., Limpijankit, V., Seesodsai, S., Panarat, P., Shanthachol, T., Sonsiri, K., Ananchuensook, P., Thanapirom, K., Suankratay, C., & Treeprasertsuk, S. (2024) · Siriraj Medical Journal/San Sirirat · doi:10.33192/smj.v76i12.270742 · Cited by 2
Multimodal Imaging Demonstrates Antifibrotic Effects of Targeting αvβ6/αvβ1 Integrins in Biliary Fibrosis
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Gopalkrishnan, K., Dodge, J. L., & Lee, B. P. (2025) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2025.07.006 · Cited by 2
Extracellular Vesicles as Biomarkers for Steatosis Stages in MASLD Patients: an Algorithmic Approach Using Explainable Artificial IntelligencePreprint
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Параметри складу тіла та коморбідність як маркери клінічно значущого фіброзу печінки (F2, F3 стадії) у пацієнтів із метаболічно-асоційованою стеатотичною хворобою печінки
Shatylo, S., Solovyova, G. A., & Кваченюк, К. Л. (2024) · Endokrynologia · doi:10.31793/1680-1466.2024.29-3.220 · Cited by 1
Lifestyle Attitudes and Habits in a Case Series of Patients With Cancer and Metabolic Syndrome
Siu, K., Leal, I. M., Heredia, N. I., Foreman, J. T., & Hwang, J. P. (2025) · American Journal of Lifestyle Medicine · doi:10.1177/15598276251319262 · Cited by 1
Noninvasive identification of metabolic dysfunction–associated steatohepatitis (INFORM MASH): a retrospective cohort and disease modeling study
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“Therefore, additional biomarkers may be used, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST to platelet ratio index (APRI), and the Fibrosis-4 (FIB-4) Index [7,8,10].”
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Feng, Y., Han, P., Liu, T., & Gao, Y. (2025) · Metabolism and Target Organ Damage · doi:10.20517/mtod.2025.65 · Cited by 1
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Sancho, M. E., Ramírez‐Manent, J. I., López, P. J. T., Campayo, I. C., Herrero, M. T. V., & López‐González, Á. A. (2025) · Gastroenterología y Hepatología (English Edition) · doi:10.1016/j.gastrohep.2025.502560 · Cited by 2
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“In studies and clinical settings, more proof is required for the longitudinal prediction of fibrosis regression and advancement and response to lifestyle and pharmacologic interventions [7].”
Influential
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“These methods have demonstrated good accuracy and are widely recommended for fibrosis assessment and risk stratification [12, 23].”
Implications of Expanded Advanced Fibrosis Screening Strategies for Metabolic Dysfunction-Associated Steatotic Liver Disease in Primary Care
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Authors: Wattacheril, J. J., Abdelmalek, M. F., Lim, J. K., & Sanyal, A. J.
Affiliations: NewYork–Presbyterian Hospital (US)
Mayo Clinic (US)
Yale University (US)
Virginia Commonwealth University (US)
Corresponding author: Wattacheril, Julia J.
ORCID: Wattacheril, Julia J.
Abdelmalek, Manal F.
Lim, Joseph K.
Sanyal, Arun J.
Venue: Gastroenterology
Publisher: Elsevier BV
Published: 2023-10
Volume: 165
Issue: 4
Pages: 1080-1088
ISSN: 0016-5085 (ISSN-L)
DOI: 10.1053/j.gastro.2023.06.013
OpenAlex: W4385567515
Cited by: 236
References: 56
Citations by year: 2026: 80 · 2025: 86 · 2024: 68 · 2023: 2
FWCI: 47.12
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: Gastroenterology (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Funders: Pfizer
Allergan
Topics: Health Sciences › Medicine › Hepatology › 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, non-invasive biomarkers, non-invasive tests, liver fibrosis, NAFLD fibrosis score, liver biopsy limitations, risk stratification, disease progression monitoring, liver disease staging, serum biomarkers, NAFLD risk prediction, NAFLD management
MeSH terms: Humans, Liver, Liver Cirrhosis, Biomarkers, Disease Progression, Non-alcoholic Fatty Liver Disease

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AGA Clinical Practice Update on the Role of Noninvasive Biomarkers in the Evaluation and Management of Nonalcoholic Fatty Liver Disease: Expert Review

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