Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings
Publication Date: May 1, 2022
Diagnosis of NAFLD in adults
Clinicians should consider persons with obesity and/or features of metabolic syndrome, those with prediabetes or T2D, and those with hepatic steatosis on any imaging study and/or persistently elevated plasma aminotransferase levels (over 6 months) to be “high risk” and screen for NAFLD and advanced fibrosis. (B, I-H, 2)
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Persons undergoing bariatric surgery should be evaluated for the presence and severity of NASH, and a liver biopsy should be considered at the time of bariatric surgery. Liver biopsy should be recommended if presurgical stratification suggests indeterminate or high risk of liver fibrosis. (B, I, 2)
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Clinicians should use liver fibrosis prediction calculations to assess the risk of NAFLD with liver fibrosis. The preferred noninvasive initial test is the FIB-4. (B, I, 2)
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Clinicians should consider persons belonging to the “high-risk” groups (as defined under R2.1.1) who have an indeterminate or high FIB-4 score for further workup with an LSM (transient elastography) or ELF test, as available. (B, I, 2)
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To stage the risk of fibrosis in persons with NAFLD, clinicians should prefer the use of VCTE as best validated to identify advanced disease and predict liver-related outcomes. Alternative imaging approaches may be considered, including shear wave elastography (less well validated) and/or magnetic resonance elastography (most accurate but with a high cost and limited availability; best if ordered by liver specialist for selected cases). (B, I, 2)
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In persons with T2D, clinicians should consider screening for clinically significant fibrosis (stages F2-F4) using the FIB-4, even if they have normal liver enzyme levels. (B, I-H, 2)
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In persons with T1D, clinicians may consider screening for NAFLD with clinically significant fibrosis (stages F2-F4) using the FIB-4, only if there are risk factors such as obesity, features of metabolic syndrome, elevated plasma aminotransferase levels (>30 U/L), or hepatic steatosis on imaging. (C, L-I, 2)
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Clinicians should further risk stratify persons with T2D, or T1D with cardiometabolic risk factors and/or elevated plasma aminotransferase levels (>30 U/L) using the FIB-4, elastography, and/or ELF test. (B, I-H, 2)
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Persons with persistently elevated ALT or AST levels and/or with hepatic steatosis on imaging and indeterminate risk (FIB-4, 1.3-2.67; LSM, 8-12 kPa; or ELF test, 7.7-9.8) or high risk (FIB-4, >2.67; LSM, >12 kPa; or ELF test, >9.8) based on blood tests and/or imaging (as described in R2.2.1, R2.2.2, and R2.3) should be referred to a gastroenterologist or hepatologist for further assessment, which may include a liver biopsy. (B, I, 2)
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Clinicians should refer persons with clinical evidence of advanced liver disease (ascites, hepatic encephalopathy, esophageal varices, or evidence of hepatic synthetic dysfunction) to a gastroenterologist/hepatologist for further care. (B, I-H, 2)
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Management of NAFLD in adults
Clinicians must manage persons with NAFLD for obesity, metabolic syndrome, prediabetes, diabetes mellitus, dyslipidemia, hypertension, and CVD based on the current standards of care. (A, I-H, 1)
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Clinicians should recommend lifestyle changes in persons with excess adiposity and NAFLD with a goal of at least 5%, preferably ≥10%, weight loss, as more weight loss is often associated with greater liver histologic and cardiometabolic benefit, depending on individualized risk assessments. Clinicians must recommend participation in a structured weight loss program, when possible, tailored to the individual’s lifestyle and personal preferences. (B, I-H, 1)
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Clinicians must recommend dietary modification in persons with NAFLD, including a reduction of macronutrient content to induce an energy deficit (with restriction of saturated fat, starch, and added sugar) and adoption of healthier eating patterns, such as the Mediterranean diet. (A, I, 1)
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In persons with NAFLD, clinicians must recommend physical activity that improves body composition and cardiometabolic health. Participation in a structured exercise program should be recommended, when possible, tailored to the individual’s lifestyle and personal preferences. (A, I, 1)
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Pioglitazone and GLP-1 RAs are recommended for persons with T2D and biopsy-proven NASH. (A, H, 1)
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Clinicians must consider treating diabetes with pioglitazone and/or GLP-1 RAs when there is an elevated probability of having NASH based on elevated plasma aminotransferase levels and noninvasive tests. (A, H, 1)
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To offer cardiometabolic benefit in persons with T2D and NAFLD, clinicians must consider treatment with GLP-1 RAs, pioglitazone, or SGLT2 inhibitors; however, there is no evidence of benefit for treatment of steatohepatitis with SGLT2 inhibitors. (A, H, 1)
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Due to the lack of evidence of efficacy, metformin, acarbose, dipeptidyl peptidase IV inhibitors, and insulin are not recommended for the treatment of steatohepatitis (no benefit on hepatocyte necrosis or inflammation) but may be continued as needed for the treatment of hyperglycemia in persons with T2D and NAFLD or NASH. (B, H, 1)
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Vitamin E can be considered for the treatment of NASH in persons without T2D, but there is not enough evidence at this time to recommend for persons with T2D or advanced fibrosis. (B, H, 1)
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Other pharmacotherapies for persons with NASH cannot be recommended at the present time due to the lack of robust evidence of clinical benefit. (A, H, 1)
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Clinicians should recommend the use of obesity pharmacotherapy as adjunctive therapy to lifestyle modification for individuals with obesity and NAFLD or NASH with a goal of at least 5%, preferably ≥10 %, weight loss, as more weight loss is often associated with greater liver histologic and cardiometabolic benefit, when this is not effectively achieved by lifestyle modification alone. (B, I, 1)
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For chronic weight management in individuals with a BMI of ≥27 kg/m2 and NAFLD or NASH, clinicians should give preference to semaglutide 2.4 mg/week (best evidence) or liraglutide 3 mg/day. (B, I-H, 1)
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Clinicians must consider obesity pharmacotherapy (with preference to semaglutide 2.4 mg/week [best evidence] or liraglutide 3 mg/day) as adjunctive therapy to lifestyle modification for individuals with obesity and NAFLD or NASH to promote cardiometabolic health and treat or prevent T2D, CVD, and other end-stage manifestations of obesity. (A, I-H, 1)
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Clinicians should consider bariatric surgery as an option to treat NAFLD (Grade B; Intermediate/Weak Strength of Evidence; BEL 2) and improve cardiometabolic health (Grade A; High/Intermediate Strength of Evidence; BEL 2; upgraded based on the cardiometabolic and all-cause mortality benefits in all persons with or without NAFLD) in persons with NAFLD and a BMI of ≥35 kg/m2 (≥32.5 kg/m2 in Asian populations), particularly if T2D is present. It should also be considered an option in those with a BMI of ≥30 to 34.9 kg/m2 (≥27.5 to 32.4 kg/m2 in Asian populations) (B, L-I, 2)
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For persons with NASH and compensated cirrhosis, clinicians should exercise caution in recommending bariatric surgery, which should be highly individualized if prescribed and performed at experienced centers. (B, L-I, 2)
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In persons with decompensated cirrhosis, bariatric surgery should not be recommended due to limited evidence and potential for harm (B, L-I, 2)
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Endoscopic bariatric and metabolic therapies and orally ingested devices should not be recommended in persons with NAFLD due to insufficient evidence. (C, L-I, 2)
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Diagnosis and management of children with NAFLD
Children of any age and adolescents with obesity or T2D, but not T1D, should be screened for NAFLD using serum ALT. (B, I-H, 2)
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Clinicians should screen adolescent females with polycystic ovary syndrome for NAFLD using serum ALT. (B, I-H, 2)
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Clinicians should screen children and adolescents with NAFLD for prediabetes or T2D using an oral glucose tolerance test if the fasting glucose level is ≥100 mg/mL or if the glycated hemoglobin (A1c) level is in the range of prediabetes (≥5.7% to 6.4%). (B, I, 2)
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Clinicians should use plasma aminotransferases to test children at high risk of NAFLD. (B, I, 2)
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Pediatric NAFLD can be diagnosed with imaging (ultrasound or magnetic resonance imaging-proton density fat fraction) or liver biopsy, in combination with exclusion of non-NAFLD causes of hepatic steatosis such as Wilson syndrome, mitochondrial disease, and medications. (B, I, 2)
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Liver fibrosis prediction calculations and proprietary biomarkers currently available for the diagnosis of advanced fibrosis in adults should not be used in children as they either are inaccurate or require further validation. (B, I, 2)
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Clinicians should recommend lifestyle changes in children with NAFLD, promoting the adoption of dietary changes to create an energy deficit, with reduction in sugar consumption as first-line lifestyle modification and increased physical activity aiming for BMI optimization. (B, I, 1)
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Clinicians may consider GLP-1 RAs for the treatment of pediatric obesity and T2D (Grade D; Expert Opinion; BEL 4), which may also offer benefit for pediatric NAFLD, although not FDA-approved for this indication. (D, L-E, 4)
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Recommendation Grading
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Overview
Title
Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings
Authoring Organization
American Association of Clinical Endocrinologists
Endorsing Organization
American Association for the Study of Liver Diseases
Publication Month/Year
May 1, 2022
Supplemental Implementation Tools
Document Type
Guideline
Country of Publication
US
Document Objectives
To provide evidence-based recommendations regarding the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) to endocrinologists, primary care clinicians, health care professionals, and other stakeholders.
Target Patient Population
All persons with NAFLD and/or NASH
Target Provider Population
Endocrinologists, primary care clinicians, health care professionals
Inclusion Criteria
Male, Female, Adolescent, Adult, Child, Older adult
Health Care Settings
Ambulatory, Outpatient
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Diagnosis, Assessment and screening, Treatment, Management
Diseases/Conditions (MeSH)
D065626 - Non-alcoholic Fatty Liver Disease, D005234 - Fatty Liver
Keywords
nonalcoholic fatty liver disease, nonalcoholic fatty liver disease (NAFLD), NAFLD, NASH, nonalcoholic steatohepatitis
Source Citation
Cusi K, Isaacs S, Barb D, Basu R, Caprio S, Garvey WT, Kashyap S, Mechanick JI, Mouzaki M, Nadolsky K, Rinella ME, Vos MB, Younossi Z. American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract. 2022 May;28(5):528-562. doi: 10.1016/j.eprac.2022.03.010. PMID: 35569886.
Supplemental Methodology Resources
Methodology
Number of Source Documents
385
Literature Search Start Date
January 1, 2010
Literature Search End Date
November 15, 2021