Cited by 7,239Liver Disease Diagnosis and TreatmentAlcohol Consumption and Health EffectsLiver Diseases and Immunity

The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases

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Chalasani, Naga, Younossi, Zobair, Lavine, Joel E., Charlton, Michael, Cusi, Kenneth, Rinella, Mary, Harrison, Stephen A., Brunt, Elizabeth M. +1 more·2018·Hepatology

Abstract

Potential conflict of interest: Dr. Chalasani consults for and received grants from Eli Lilly. He consults for NuSirt, AbbVie, Afimmune, Tobira, Madrigal, Shire, Cempra, Ardelyx, Axovant, and Amarin. He received grants from Intercept, Gilead, Galectin, and Cumberland. Dr. Younossi consults for Bristol‐Myers Squibb, Gilead, Intercept, Allergan, and GlaxoSmithKline. He advises for Vertex and Janssen. Dr. Brunt advises for Gilead. Dr. Charlton consults for and received grants from Gilead, Intercept, NGM Bio, Genfit, and Novartis. He received grants from Conatus. Dr. Cusi consults for and received grants from Novo Nordisk. He consults for Tobira. He received grants from Cirius, Novartis, Janssen, Zydus, Nordic, and Lilly. Dr. Rinella consults for Intercept, Gilead, Genfit, Novartis, NGM Bio, and Nusirt. She advises for Fibrogen, Immuron, Enanta, and AbbVie. Dr. Harrison consults for Madrigal, NGM Bio, Genfit, Echosens, Prometheus, Cirius, Perspectum, and HistoIndex. He advises for Garland, Intercept, Novartis, and Pfizer. He is on the speakers' bureau for AbbVie, Gilead, and Alexion. Dr. Sanyal consults for and received grants from Salix, Conatus, Galectin, Gilead, malinckrodt, Echosens‐Sandhill, Novartis, and Sequana. He consults for and is employed by Sanyal Bio. He consults for and owns stock in GenFit, Hemoshear, Durect, and Indalo. He consults for Immuron, Intercept, Pfizer, Boehringer Ingleheim, Nimbus, Nitto Denko, Lilly, Novo Nordisk, Fractyl, Allergan, Chemomab, Affimmune, Teva, and Ardelyx. He received grants from Bristol‐Myers Squibb and Merck. He received royalties from UptoDate. He owns stock in Exhalenz, Arkana, and NewCo LLC. The funding for the development of this Practice Guidance was provided by the American Association for the Study of Liver Diseases. This practice guidance was approved by the American Association for the Study of Liver Diseases on June 15, 2017. Preamble This guidance provides a data‐supported approach to the diagnostic, therapeutic, and preventive aspects of nonalcoholic fatty liver disease (NAFLD) care. A “Guidance” document is different from a “Guideline.” Guidelines are developed by a multidisciplinary panel of experts and rate the quality (level) of the evidence and the strength of each recommendation using the Grading of Recommendations, Assessment Development, and Evaluation system. A guidance document is developed by a panel of experts in the topic, and guidance statements, not recommendations, are put forward to help clinicians understand and implement the most recent evidence. This Practice Guidance was commissioned by the American Association for the Study of Liver Diseases (AASLD) and is an update to the Practice Guideline published in 2012 in conjunction with the American Gastroenterology Association and the American College of Gastroenterology (ACG).1 Sections where there have been no notable newer publications are not modified, so some paragraphs remain unchanged. This narrative review and guidance statements are based on the following: (1) a formal review and analysis of the recently published world literature on the topic (Medline search up to August 2016); (2) the American College of Physicians' Manual for Assessing Health Practices and Designing Practice Guidelines2; (3) guideline policies of the AASLD; and (4) the experience of the authors and independent reviewers with regard to NAFLD. This practice guidance is intended for use by physicians and other health professionals. As clinically appropriate, guidance statements should be tailored for individual patients. Specific guidance statements are evidence based whenever possible, and, when such evidence is not available or is inconsistent, guidance statements are made based on the consensus opinion of the authors.3 This is a practice guidance for clinicians rather than a review article, and interested readers can refer to several recent comprehensive reviews.4 Because this guidance document is lengthy, to make it easier for the reader, a list of all guidance statements and recommendations are provided in a tabular form as Supporting Table S1. Definitions For defining NAFLD, there must be (1) evidence of hepatic steatosis (HS), either by imaging or histology, and (2) lack of secondary causes of hepatic fat accumulation such as significant alcohol consumption, long‐term use of a steatogenic medication, or monogenic hereditary disorders (Table 1). In the majority of patients, NAFLD is commonly associated with metabolic comorbidities such as obesity, diabetes mellitus, and dyslipidemia. NAFLD can be categorized histologically into nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH; Table 2). NAFL is defined as the presence of ≥5% HS without evidence of hepatocellular injury in the form of hepatocyte ballooning. NASH is defined as the presence of ≥5% HS and inflammation with hepatocyte injury (e.g., ballooning), with or without any fibrosis. For defining “advanced” fibrosis, this guidance doc

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  • Positive side effects of Pioglitazone include improvement of insulin sensitivity and diabetic control.

    “Positive side effects of Pioglitazone treatment being improvement of insulin sensitivity and diabetic control”

    From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [6]

    The guidance’s pioglitazone trial discussion (page unavailable) reports improved insulin sensitivity in patients with NASH and prediabetes or type 2 diabetes. It also describes metabolic improvements, but does not specifically report improved diabetic control, so that part of the claim is not established by our copy. (LLM, conf=0.83)

    Experimental — accuracy not yet measured
  • The AASLD practice guidance states that Vitamin E (800 IU/day) may be considered for treating non-diabetic patients with NASH.

    “the current practice guidance endorsed by the AASLD states that Vitamin E (800 IU/day) “may be considered” for treating non‐diabetic patients with NASH [6].”

    From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [6]

    Guidance Statement 27 (Vitamin E section) says 800 IU/day may be considered, but specifically for nondiabetic adults with biopsy-proven NASH. The citing sentence omits the adult and biopsy-proven qualifications, making its patient group broader than the guidance states. (LLM, conf=0.84)

    Experimental — accuracy not yet measured
  • Only Vitamin E and Pioglitazone are recommended for selected NAFLD patients by the European and American Association for the Study of the Liver.

    “currently, only Vitamin E and the proliferator‐activated receptor gamma (PPAR‐y) ligand Pioglitazone are recommended for selected patients by the European‐ and American Association for the Study of the Liver [5, 6].”

    From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [6]

    The guidance statements (page not available in our copy) say vitamin E may be considered for nondiabetic adults with biopsy-proven NASH, and the Thiazolidinediones section discusses benefits of pioglitazone in NASH. This supports considering the two drugs for selected patients under the American guidance, but the cited passages do not establish that they are the only recommended treatments or extend that recommendation to NAFLD patients generally. This American guidance does not establish the European association’s position, which the sentence also cites separately. (LLM, conf=0.83)

    Experimental — accuracy not yet measured
  • Possible side effects of Vitamin E include increased bleeding risk, prostate cancer, heart failure and hemorrhagic stroke, though they are rarely seen.

    “Possible side effects of Vitamin E include an increased bleeding risk, prostate cancer, heart failure and hemorrhagic stroke and those should be discussed with the patient, even though they are rarely seen [4, 6].”

    From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [6]

    The Vitamin E section reports a modest increase in prostate-cancer risk in a trial and advises discussing risks and benefits with patients (page unavailable in our copy). It does not identify increased bleeding risk, heart failure, or hemorrhagic stroke as vitamin E side effects, or say that the listed effects are rarely seen. (LLM, conf=0.88)

    Experimental — accuracy not yet measured
  • Negative side effects of Pioglitazone include weight gain, fluid retention, bone loss and a possible increase in bladder cancer.

    “negative side effects including weight gain, fluid retention, bone loss and a possible increase in bladder cancer [4, 6].”

    From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [6]

    The Thiazolidinediones section identifies weight gain as a common side effect of pioglitazone, says bone loss may occur in women treated with thiazolidinediones, and describes mixed evidence on a possible bladder-cancer association. It does not identify fluid retention as a pioglitazone side effect; the copy mentions fluid retention only in a separate discussion of transplant candidates’ BMI. Page numbers were not available in the indexed passages. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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References 286 · Cited by 7,239

Research works printed but not linked: 5

  1. Vuppalanchi R, Siddiqui MS, Hallinan EK, Abdelmalek MF, Neuschwander-Tetri B, Loomba R, et al. Transient elastography is feasible with high success rate for evaluation of non-alcoholic fatty liver disease (NAFLD) in a multicenter setting. Hepatology. 2015;62:1290A. (74) 7/11/2017
  2. AASLD approved version submitted to HEPATOLOGY on June 28, 2017 resistance in patients with non-alcoholic steatohepatitis: results of a pilot study. Intern Med J. 2007;37:229-235.
  3. AASLD approved version submitted to HEPATOLOGY on June 28, 2017 nonalcoholic steatohepatitis (NASH) patients with dyslipidemia: clinical usefulness of AGEs as a biomarker for the attenuation of NASH. J Gastroenterol. 2010;45:750-757.
  4. Kim TN, Park MS, Lim KI, Choi HY, Yang SJ, Yoo HJ, et al. Relationships between sarcopenic obesity and insulin resistance, inflammation, and vitamin D status: the Korean Sarcopenic Obesity Study. Clin Endocrinol (Oxf). 2013;78:525-532.
  5. Lavine JE, Yates KP, Brunt EM, Kleiner DE, Schwimmer D, Murray KF, et al. The natural history of nonalcoholic fatty liver disease in children and adolescents assessed in placebo recipients in the TONIC trial. Hepatology. 2012;56:905A.

Authors
Chalasani, N., Younossi, Z., Lavine, J. E., Charlton, M., Cusi, K., Rinella, M., Harrison, S. A., Brunt, E. M., & Sanyal, A. J.
Affiliations
  • Indiana University School of Medicine (US)
  • Inova Fairfax Hospital (US)
  • Columbia University (US)
  • University of Chicago (US)
  • University of Florida (US)
  • Northwestern University (US)
  • Pinnacle Clinical Research (US)
  • Washington University in St. Louis (US)
  • Virginia Commonwealth University (US)
Corresponding author
Chalasani, Naga
Venue
Hepatology
Published
2017-09-29
Volume
67
Issue
1
Pages
328-357
ISSN
  • 0270-9139 (ISSN-L)
  • 1527-3350
OpenAlex
W2734724639
Cited by
7,239
References
286
Citations by year
2026: 417 · 2025: 704 · 2024: 901 · 2023: 1043 · 2022: 1138 · 2021: 1103 · 2020: 886 · 2019: 591 · 2018: 294 · 2017: 64 · 2016: 67 · 2015: 14 · 2013: 1 · 2012: 2
FWCI
393.57
Type
journal article
Language
en
Open access
Locations
  • Hepatology (publishedVersion)
  • PubMed (publishedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
  • Purdue University Indianapolis (Indiana University) (submittedVersion)
Funders
  • Bristol-Myers Squibb
  • Eli Lilly and Company
  • American Association for the Study of Liver Diseases
  • Gilead Sciences
  • Amarin Corporation
  • NGM Biopharmaceuticals
  • Novo Nordisk
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Keywords
non-alcoholic fatty liver disease, diagnosis, management, steatosis, liver fibrosis, noninvasive fibrosis assessment
MeSH terms
Adolescent, Adult, Child, Humans, Mass Screening, Obesity, Incidence, Prevalence, Liver Transplantation, Disease Management, Non-alcoholic Fatty Liver Disease

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