2017/07/17 by Naga Chalasani, Zobair Younossi, Zobair M. Younossi +8 · 19 citations
Medicine · #Diet, Metabolism, and Disease #Liver Disease Diagnosis and Treatment #Liver Disease and Transplantation
paper · pdf · doi:10.1002/hep.29367
openalex publication_date 2017/07/17 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
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 document will be referring specifically to stages 3 or 4, that is, bridging fibrosis or cirrhosis. Table 1 - Common Causes of Secondary HS Macrovesicular steatosis ‐ Excessive alcohol consumption ‐ Hepatitis C (genotype 3) ‐ WD ‐ Lipodystrophy ‐ Starvation ‐ Parenteral nutrition ‐ Abetalipoproteinemia ‐ Medications (e.g., mipomersen, lomitapide, amiodarone, methotrexate, tamoxifen, corticosteroids) Microvesicular steatosis ‐ Reye's syndrome ‐ Medications (valproate, antiretroviral medicines) ‐ Acute fatty liver of pregnancy ‐ HELLP syndrome ‐ Inborn errors of metabolism (e.g., lecithin‐cholesterol acyltransferase deficiency, cholesterol ester storage disease, Wolman's disease) Table 2 - NAFLD and Related Definitions NAFLD Encompasses the entire spectrum of FLD in individuals without significant alcohol consumption, ranging from fatty liver to SH to cirrhosis NAFL Presence of ≥5% HS without evidence of hepatocellular injury in the form of ballooning of the hepatocytes or evidence of fibrosis. The risk of progression to cirrhosis and liver failure is considered minimal. NASH Presence of ≥5% HS with inflammation and hepatocyte injury with or without fibrosis. 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