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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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“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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“14 Alargenumberofstudieshavebeenconductedtoassess the relationship between NAFLD and overall dietary patterns, 15 – 17 as well as different nutritional components, 18 – 20 implicating saturated fatty acids (SFAs) 21 – 23 and added fructose, mainly in the form ofsucrose( i.e.…”
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“However, any type of dietary pattern or food composition aimed at calorie restriction with long-term sustainability would improve features of MASLD [11].”
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“6 The idea is to use a simple fibrosis score such as the Fibrosis-4 index (FIB-4) for initial assessment.”
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“However, bariatric surgery has the potential to achieve sustained weight loss of up to 30% and may also lead to the resolution of MASLD [126,181].”
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“Per new AASLD MASLD guidance in 2023, the management of lean individuals with MASLD emphasizes dietary modifications and exercise to improve insulin resistance since recommending weight loss may not be appropriate for some lean patients with MASLD [78].”
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“The current recommendations for management focus on lifestyle modifications, which include physical activity with aerobic exercise, resistance exercise, weight loss, and strict adherence to a Mediterranean diet[14,15].”
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“Vitamin E can be prescribed as an adjunct for pediatric and adult patients with MASH in the absence of type 2 diabetes as 400 mg IU twice daily or 800 mg IU daily to improve steatosis [6].”
InfluentialMASH clinical trials and drugs pipeline: An impending tsunami
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“A larger study (SEMA-NASH) enrolling 320 individuals with obesity, biopsy-proven NASH and differentdegreesof fi brosis,withorwithoutdiabetes,demonstratedthatOD subcutaneous semaglutide 0.4 mg signi fi cantly resolved MASH without worsening fi brosis in 59% of patients 93 .”
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“2,34 While liver biopsy is a cornerstone in MASH diagnosis, it is invasive and expensive.”
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“Consequently, absolute abstention from alcohol consumption in patients with NAFLD/MAFLD is recommended by international guidelines [48].”
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“[122] The Mediterranean diet is recommended for patients with MASLD and is associated with cardiovascular benefits.”
Pharmaco‐Economic Assessment of Screening Strategies for High‐Risk MASLD in Primary Care
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“In contrast, AASLD/AACE recommend that individuals with a high-risk FIB-4 score ( ≥ 2.67) be referred directly to specialists without undergoing a second-line test in primary care [9, 10].”
InfluentialNonalcoholic fatty liver disease: Current therapies and future perspectives in drug delivery
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“33,37,38 This should be achieved using non-invasive (NI) tests with high negative predictive value aimed at 'ruling out' fibrosis.”
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“[2,3] 6] A few retrospective studies have assessed the association between the PNPLA3 rs738409 variant and overall mortality.”
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“Currently, the first line of treatment for compensated cirrhosis in patients with MASH and obesity is lifestyle interventions 3,29 .”
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“9 Internationally, a daily intake of less than 20 g of alcohol in women, and less than 30 g in men, is usually recommended to define the presence of NAFLD and rule out ALD in the setting of hepatic steatosis.”
BackgroundNatural history of lean and non-lean metabolic dysfunction-associated steatotic liver disease
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“NAFLD guidelines recommend paying attention to CVEs [46–48]; however, the consideration for CVE risk may differ in lean MASLD compared with non-lean MASLD.”
High inherited risk predicts age-associated increases in fibrosis in patients with MASLD
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“[14] Dietary modifications are associated with reductions in steatosis among patients with established MASLD.”
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“Bariatric surgery was less recognised as a possible treatment for NAFLD, whilst it is one of the few medical interventions included in guidelines yet.(30,31) Although 65% of physicians use available practice guidelines to manage NAFLD patients, 11% were unaware of the existence of these guidelines at all.”
BackgroundDigital pathology for nonalcoholic steatohepatitis assessment
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“[12] The optimal strategy to validate this approach would require that all participants undergo an accurate assessment to define the true prevalence of advanced fibrosis across low-, indeterminate-risk, and high-risk groups.”
BackgroundSelf-citation
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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