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AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease
Open accessAbstract
PREAMBLE The study of NAFLD has intensified significantly, with more than 1400 publications since 2018, when the last American Association for the Study of Liver Diseases (AASLD) Guidance document was published.1 This new AASLD Guidance document reflects many advances in the field pertinent to any practitioner caring for patients with NAFLD and emphasizes advances in noninvasive risk stratification and therapeutics. A separate guideline focused on the management of patients with NAFLD in the context of diabetes has been written jointly by the American Association of Clinical Endocrinology and AASLD.2 Given the significant growth in pediatric NAFLD, it will not be covered here to allow for a more robust discussion of the diagnosis and management of pediatric NAFLD in the upcoming AASLD Pediatric NAFLD Guidance. A “Guidance” differs from a “Guideline” in that it is not bound by the Grading of Recommendations, Assessment Development and Evaluation system. Thus, actionable statements rather than formal recommendations are provided herein. The highest available level of evidence was used to develop these statements, and, where high-level evidence was not available, expert opinion was used to develop guidance statements to inform clinical practice. Key points highlight important concepts relevant to understanding the disease and its management. The most profound advances in NAFLD relevant to clinical practice are in biomarkers and therapeutics. Biomarkers and noninvasive tests (NITs) can be used clinically to either exclude advanced diseases or identify those with a high probability of cirrhosis.3,4 NIT “cut points” vary with the populations studied, underlying disease severity, and clinical setting. Those proposed in this guidance are meant to aid decision-making in the clinic and are not meant to be interpreted in isolation. Identifying patients with “at-risk” NASH (biopsy-proven NASH with stage 2 or higher fibrosis) is a more recent area of interest. Although the definitive diagnosis and staging of NASH remain linked to histology, noninvasive tools can now be used to assess the likelihood of significant fibrosis, predict risk of disease progression and decompensation, make management decisions, and, to some degree, assess response to treatment. There is an ongoing debate over the nomenclature of fatty liver disease, which had not been finalized at the time this guidance was published. At the culmination of a rigorous consensus process, it is intended that any formal change in nomenclature will advance the field without a negative impact on disease awareness, clinical trial endpoints, or the drug development/approval process. Furthermore, it should allow for the emergence of newly recognized disease subtypes to address the impact of disease heterogeneity, including the role of alcohol, on disease progression and response to therapy. Input from patients has been central to all stages of the consensus process to ensure the minimization of nomenclature-related stigma. DEFINITIONS NAFLD is an overarching term that includes all disease grades and stages and refers to a population in which ≥5% of hepatocytes display macrovesicular steatosis in the absence of a readily identified alternative cause of steatosis (eg, medications, starvation, monogenic disorders) in individuals who drink little or no alcohol (defined as < 20 g/d for women and <30 g/d for men). The spectrum of disease includes NAFL, characterized by macrovesicular hepatic steatosis that may be accompanied by mild inflammation, and NASH, which is additionally characterized by the presence of inflammation and cellular injury (ballooning), with or without fibrosis, and finally cirrhosis, which is characterized by bands of fibrous septa leading to the formation of cirrhotic nodules, in which the earlier features of NASH may no longer be fully appreciated on a liver biopsy. UPDATE ON EPIDEMIOLOGY AND NATURAL HISTORY The prevalence of NAFLD and NASH is rising worldwide in parallel with increases in the prevalence of obesity and metabolic comorbid disease (insulin resistance, dyslipidemia, central obesity, and hypertension).5,6 The prevalence of NAFLD in adults is estimated to be 25%–30% in the general population7–9 and varies with the clinical setting, race/ethnicity, and geographic region studied but often remains undiagnosed.10–14 The associated economic burden attributable to NASH is substantial.15–17 The prevalence of NASH in the general population is challenging to determine with certainty; however, NASH was identified in 14% of asymptomatic patients undergoing colon cancer screening.14 This study also highlights that since the publication of a prior prospective prevalence study,18 the prevalence of clinically significant fibrosis (stage 2 or higher fibrosis) has increased >2-fold. This is supported by the projected rise in NAFLD prevalence by 2030, when patients with advanced hepatic fibrosis, defined as bridging fibrosis (F3) or compensated will the proj
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“Based on this, it seems reasonable to conclude that should patients continue to complete guideline-based amounts of aerobic exercise over a longer duration, fibrosis improvement may follow [35, 36].”
From Aerobic Exercise Training Leads to MASH Resolution as Defined by the MASH Resolution Index (2026) · cites this paper as [35]
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“Moreover, interventions in diet and physical activity are considered to be the cornerstone of management in the whole MASLD spectrum [7, 10].”
From Effects of Mediterranean diet, exercise, and their combination on body composition and liver outcomes in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis of randomized controlled trials (2025) · cites this paper as [7]
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In the citing paper
“Although there is no consensus on the optimal diet for treating MASLD, the EASL-EASD-EASO guidelines recently recommended the MD as the preferred option [7, 10].”
From Effects of Mediterranean diet, exercise, and their combination on body composition and liver outcomes in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis of randomized controlled trials (2025) · cites this paper as [7]
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“Current guidelines recommend weight loss through dietary modifications, increased physical activity, or both combined in MASLD patients [7, 11, 12].”
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“Various scienti fi c societies have recommended clinical care pathways with an emphasis on the use of non-invasive tests (NITs) and the liaison between primary care/non-hepatology and hepatology settings.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [126]
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“GLP-1RA-based drugs have been proven beneficial to some extent in dedicated trials and should be considered in patients with obesity and/or T2D and metabolic dysfunction-associated steatohepatitis (MASH)90.”
From Incretin-based therapies for the treatment of obesity-related diseases (2024) · cites this paper as [90]
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“56 Our study had some limitations.”
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“Consequently, a total of 1,585 individuals meeting the diagnostic threshold of CAP ≥ 248 dB/m were identified as having NAFLD [19, 20].”
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Zhang, X., Gong, Y., & Sun, C. (2025) · Journal of Functional Foods · doi:10.1016/j.jff.2025.106784 · Cited by 5
New steatotic liver disease criteria diagnostic performance in an agricultural population in Chile
Spencer-Sandino, M., Godoy, F., Huidobro, A., Alvares, D., Cruz, F., Marco, C., Garrido, M., Cabrera, D., Arab, J. P., Arrese, M. A., et al. (2025) · Annals of Hepatology · doi:10.1016/j.aohep.2025.101919 · Cited by 5
de Jong, V., Alings, M., Brůha, R., Cortez‐Pinto, H., Dedoussis, G. V., Doukas, M., Francque, S., Fournier, C., Gastaldelli, A., Hankemeier, T., et al. (2025) · BMJ Open · doi:10.1136/bmjopen-2024-092731 · Cited by 6
The OGT–TFF2 axis mediates intrahepatic crosstalk and MASH pathogenesis
Zhang, L., Han, C., Shrestha, M. M., Le, J., Berger, W. K., Huang, Y., Desrouleaux, R., Wang, E., Nagy, L., & Yang, X. (2025) · Hepatology · doi:10.1097/hep.0000000000001445 · Cited by 5
Gries, J. J., Chen, B., Bansal, M. B., Rodríguez, M., Alqahtani, S. A., Brennan, P., Lang, C. C., Tang, W. H. W., Lazarus, J. V., & Krittanawong, C. (2025) · Communications Medicine · doi:10.1038/s43856-025-00951-2 · Cited by 6
“Notably, metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH) 10 , the most severe form of MASLD, already ranks as the primary indication for liver transplantation in women and those over age 65 1 .”
Lei, Y., Zhu, Y., Ni, W., Shi, J., Seto, W., & Li, J. (2025) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.70335 · Cited by 5
Cui, J., Wang, W., Xu, Q., Zhu, M., Li, Y., Liu, Y., & Liu, Y. (2025) · Journal of the American Heart Association · doi:10.1161/jaha.124.040775 · Cited by 5
“For the prevention and treatment of MAFLD, updated guidelines have been proposed by the American Association for the Study of Liver Diseases (2023), 66 and the European Association for the Study of the Liver (2024).”
Protective Role of Coffee in Chronic Liver Disease: A Focus on Processing
Khalifa, R., Al-Naamani, K. M., Elbadry, M., Zhang, Y., Alswat, K., & El‐Kassas, M. (2025) · Journal of Viral Hepatitis · doi:10.1111/jvh.70072 · Cited by 5
“Consequently, the American Association for the Study of Liver Diseases (AASLD) recommends that individuals consume black caffeinated coffee in quantities of at least three cups per day [46].”
Sualeheen, A., Tan, S., Daly, R. M., Georgousopoulou, E. N., Roberts, S. K., & George, E. S. (2025) · European Journal of Nutrition · doi:10.1007/s00394-025-03809-4 · Cited by 5
Rohani, P., Shojaie, S., Nikparast, A., Shaygantabar, M., Marvasti, F. E., Asghari, G., Ejtahed, H., Sohouli, M. H., Hasani‐Ranjbar, S., Siadat, S. D., et al. (2025) · BMC Pediatrics · doi:10.1186/s12887-025-06144-z · Cited by 5
“Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), refers to hepatic fat accumulation not attributed to excessive alcohol intake or other known liver pathologies [1].”
van Kleef, L. A., Savas, M., Michel, M. S., Caussy, C., Pustjens, J., Holleboom, A. G., van Rossum, E. F. C., Janssen, H. L. A., Schattenberg, J. M., & Brouwer, W. P. (2025) · Gastro Hep Advances · doi:10.1016/j.gastha.2025.100831 · Cited by 5
Discovery of ultrasound-derived fat fraction as a non-invasive tool for MASLD diagnosis
Jin, H., Jiao, M., Yu, C., Ren, T., Chen, Q., Dai, Z., Xie, E., Jiang, L., & Li, Y. (2025) · European journal of medical research · doi:10.1186/s40001-025-03229-4 · Cited by 5
“MASLD was defined as MRI-PDFF of 5% or higher [9].”
Improvement of Liver Fibrosis in Patients with MASLD Undergoing Pioglitazone Treatment: An Update
Stasi, C., & Mega, A. (2025) · Life · doi:10.3390/life15111682 · Cited by 5
“The AASLD guidelines [6] suggest that pioglitazone improves MASH and can be considered for patients with MASH in the presence of T2DM.”
Lazarus, J. V., Agirre‐Garrido, L., Miralles‐Sanchez, J. E., Manolas, M. I., Tacke, F., Villela‐Nogueira, C. A., Al‐Omar, H. A., Alqahtani, S. A., Alzubaidi, L. M. Y., Bansal, M. B., et al. (2025) · Liver International · doi:10.1111/liv.70390 · Cited by 5
Review Article: The Evolving Role of GLP ‐1 Receptor Agonists in Gastroenterology Practice
Pomenti, S. F., Gerber, A. R., Katzka, D. A., Camilleri, M., & Hur, C. (2025) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.70450 · Cited by 6
“Given the significant weight loss achieved with these medications, their use is strongly recommended by GI societies [9, 10].”
Heyens, L. J. M., Innocenti, F., Steenkiste, C. V., Struyve, M., Francque, S., Koek, G. H., & Robaeys, G. (2025) · Biomedicines · doi:10.3390/biomedicines13112821 · Cited by 7
“According to the guidelines of the European Study of the Liver and the American Association for the Study of the Liver, screening for fibrosis in T2DM is also recommended; however, prediabetes is scarcely addressed, and the guidelines are unclear [19,42].”
Li, D., & Zhang, X. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000846 · Cited by 8
“[45] MASLD patients with biopsy-proven bridging fibrosis displayed a baseline VCTE LSM of 16.6 kPa or greater, and progression to cirrhosis would increase by at least 20% in VCTE LSM. [46] However, the accuracy of VCTE will also be interfered with by obesity, as well as other confounding factors,…”
InfluentialAbdelhamed, W., Amin, M. A., Waked, I. A., & El‐Kassas, M. (2025) · World Journal of Gastroenterology · doi:10.3748/wjg.v31.i45.111643 · Cited by 5
“As a result, recent clinical guidelines recommend routine MASLD fibrosis screening in all T2DM patients[31,32].”
InfluentialScreening and management of metabolic dysfunction-associated steatotic liver disease (MASLD)
Geary, A. (2025) · JAAPA · doi:10.1097/01.jaa.0000000000000296 · Cited by 5
Ketogenic diets and metabolic dysfunction-associated steatotic liver disease: a literature review
Sun, K., Li, W., Chen, Y., Nelson, E. A. S., Chen, X., & Hui, L. L. (2025) · Cell & Bioscience · doi:10.1186/s13578-025-01494-8 · Cited by 7
“It is generally agreed among major hepatol-ogy associations that a weight loss of 7–10% improves hepatic steatosis in patients with overweight and obesity, and > 10% weight loss can improve inflammation and fibrosis [19, 20, 51, 52].”
InfluentialLou, J.-J., & Zeng, J. (2025) · World Journal of Gastroenterology · doi:10.3748/wjg.v31.i47.111900 · Cited by 8
“Routine screening relies on serologic markers, risk scores, and imaging [ e.g. , ultrasound, computed tomography (CT)], which have limited sensitivity for mild steatosis and early fibrosis and are affected by operator and equipment variability[13-15].”
Williams, G. M., Hoedt, E. C., Duncanson, K., Gan, L. T., Prakoso, E., Talley, N. J., & Beck, E. J. (2025) · Nutrition & Metabolism · doi:10.1186/s12986-025-00939-8 · Cited by 5
Li, Q., Feng, M., luo, Q., Ye, C. Y., Luo, Y. K., & Xu, Y. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1715364 · Cited by 5
Xiang, S., Li, Y., Li, Y., Xie, S., Wang, C., Che, X., & Du, Y. (2026) · The journal of nutrition health & aging · doi:10.1016/j.jnha.2026.100775 · Cited by 6
“These patterns are consistent with current clinical management guidelines that emphasize lifestyle modification in GERD and NAFLD care [66].”
Convergent Metabolic Pathways in MASH Therapeutics: An AMPK ‐Centric Analysis
Choi, S., Jung, J., Seo, Y., Song, S., Ham, J., Chung, H., Ramadan, Y., & Choi, K. (2026) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.71023 · Cited by 5
Epidemiology and diagnostic of MASLD in Latin America: a yet to be met challenge
Olaez-Ramos, C. E., Mojica-Zamudio, K. L., Sandoval-Rodriguez, A. S., & Armendáriz‐Borunda, J. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1700072 · Cited by 7
“Noninvasive screening tools serve a vital role as initial screening instruments, providing a cost-effective and accessible method for identifying individuals at elevated risk who may warrant subsequent confirmatory investigation (Rinella et al., 2023a; Rinella et al., 2023b; Tacke et al., 2024).”
InfluentialAssessing Nutraceuticals for Hepatic Steatosis: A Standardized In Vitro Approach
Palasantzas, V. E. J. M., Struik, D., Bos, T., Withoff, S., Fu, J., Jonker, J. W., & Hoogerland, J. A. (2026) · Nutrients · doi:10.3390/nu18030388 · Cited by 5
“Vitamin E is currently the only phytochemical recommended off-label for MASLD patients without diabetes [21,24], although the evidence for its efficacy in improving steatohepatitis and fibrosis is limited and hepatotoxicity has been reported [25–27].”
Noninvasive liver fibrosis assessment in metabolic dysfunction-associated steatotic liver disease
Ribeiro, T. C. R., Soares, V. D. P. B., Fabri, J. C., & Ramos, L. E. D. A. (2026) · World Journal of Hepatology · doi:10.4254/wjh.v18.i1.111534 · Cited by 5
Li, X., Miao, X., Zhang, X., Tian, H., Wang, L. C., Liu, J., Zhang, J., Tan, R., & Huang, J. (2026) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.5c15040 · Cited by 5
Liver Biopsy in Metabolic-Associated Steatotic Liver Disease: Accuracy, Challenges, and Alternatives
Borz-Baba, L., Aydin, A., & Parvin, R. (2026) · Cureus · doi:10.7759/cureus.103284 · Cited by 5
Ghodrati, F., Zhang, A. B., & Mahmud, N. (2026) · Gastroenterology report · doi:10.1093/gastro/goag006 · Cited by 6
“Current US and European guidelines recommend using a stepwise approach with the fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE) to stage fibrosis and risk stratify MASLD patients [14, 23, 59–61].”
Athinarayanan, S. J., Wolfberg, A., Shanmugam, P., Hameed, B., & Bonacini, M. (2026) · Hepatology · doi:10.1097/hep.0000000000001713 · Cited by 5
Alexa, R.-E., Haliga, R. E., Morărașu, B. C., Ceasovschih, A., Sîrbu, O., Asaftei, A., Șorodoc, V., & Șorodoc, L. (2026) · Medical Sciences · doi:10.3390/medsci14020160 · Cited by 7
Reinson, T., Bilson, J., Childs, C. E., Buchanan, R. M., Targher, G., & Byrne, C. D. (2026) · BMJ Medicine · doi:10.1136/bmjmed-2025-002038 · Cited by 9
Liu, M., Ma, Y., Cheang, W. S., Su, Z., & Xu, S. (2026) · Molecular Therapy · doi:10.1016/j.ymthe.2026.04.011 · Cited by 8
Oxidative Stress and Alcohol-Related Hepatitis: A Role for Future Therapies
D’Arcangelo, F., Rajoriya, N., & Lalor, P. F. (2026) · Antioxidants · doi:10.3390/antiox15040493 · Cited by 6
“Vitamin E, a lipid-soluble antioxidant, has demonstrated efficacy in NAFLD/NASH with reductions in ALT and AST levels and is recommended by AASLD guidelines [135] for MASLD patients.”
Georgakopoulou, V., Steiropoulos, P., Androutsakos, T., Karabella, I., Reppas, K., Cholongitas, E., & Dalamaga, M. (2026) · Current Obesity Reports · doi:10.1007/s13679-026-00713-8 · Cited by 5
Gee, M. F. W., Fonstad, R. K., Vol, E. B. D., Brown, C., Feld, J. J., Patel, K., & Sanyal, A. J. (2026) · Hepatology Communications · doi:10.1097/hc9.0000000000000931 · Cited by 5
“[7,8] Consequently, several noninvasive tests (NITs) have been developed to aid in the prognostication of MASH, including the Enhanced Liver Fibrosis (ELF) Test.”
InfluentialMiwa, T., Díaz, L. A., Harberts, A., Yukawa‐Muto, Y., Nakamura, T., Zhang, X., Loomba, R. S., & Schnabl, B. (2026) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.70711 · Cited by 5
“In addition, SLD contributes to extrahepatic complications such as major adverse cardiovascular events (MACEs) and increased overall mortality [10].”
Self-citationGál, A. R., Szokodi, I., Vizvári, Z., Győrfi, N., Vereczkei, A. G., Petykó, Z., Karádi, Z., & Tóth, A. (2026) · Antioxidants · doi:10.3390/antiox15060710 · Cited by 6
“Liver ultrasound provides a semi-quantitative assessment of hepatic steatosis; however, the absence of sonographic steatosis does not rule out MASLD, metabolic dysfunction-associated steatohepatitis (MASH), or hepatic fibrosis [203,204].”
Wang, B., Zeng, X., Deng, H., Qiu, B., Xu, K., Tao, M., Zhang, Y., Zheng, H., Xu, Q., Li, S., et al. (2026) · Metabolism · doi:10.1016/j.metabol.2026.156677 · Cited by 7
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Screening for At-Risk Nonalcoholic Fatty Liver Disease in the Primary Care Setting
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Metadata
- Authors
- Rinella, M. E., Neuschwander-Tetri, B. A., Siddiqui, M. S., Abdelmalek, M. F., Caldwell, S., Barb, D., Kleiner, D. E., & Loomba, R.
- Affiliations
- University of Chicago (US)
- Saint Louis University School of Medicine, Saint Louis, Missouri, USA
- Virginia Commonwealth University (US)
- Mayo Clinic (US)
- University of Virginia (US)
- University of Florida Health (US)
- National Institutes of Health (US)
- University of California San Diego (US)
- Corresponding author
- Rinella, Mary E.
- ORCID
- Venue
- Hepatology
- Published
- 2023-03-17
- Volume
- 77
- Issue
- 5
- Pages
- 1797-1835
- ISSN
- 0270-9139 (ISSN-L)
- PMC
- PMC10735173
- OpenAlex
- W4318923555
- Cited by
- 2,667
- References
- 502
- Citations by year
- 2026: 849 · 2025: 845 · 2024: 691 · 2023: 281
- FWCI
- 532.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Bristol-Myers Squibb
- American Association for the Study of Liver Diseases
- NGM Biopharmaceuticals
- Novo Nordisk
- National Institutes of Health
- Allergan
- National Cancer Institute (ZICBC010685)
- 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, nonalcoholic steatohepatitis, non-invasive risk stratification, non-invasive tests, fibrosis staging, liver cirrhosis
- MeSH terms
- Humans, Liver, Liver Cirrhosis, Disease Progression, Non-alcoholic Fatty Liver Disease
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