AGA Clinical Practice Update: Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Lean Individuals: Expert Review

Gastroenterology. 2022 Sep;163(3):764-774.e1. doi: 10.1053/j.gastro.2022.06.023. Epub 2022 Jul 14.


Description: Nonalcoholic fatty liver disease (NAFLD) is well recognized as a leading etiology for chronic liver disease, affecting >25% of the US and global populations. Up to 1 in 4 individuals with NAFLD have nonalcoholic steatohepatitis, which is associated with significant morbidity and mortality due to complications of liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Although NAFLD is observed predominantly in persons with obesity and/or type 2 diabetes mellitus, an estimated 7%-20% of individuals with NAFLD have lean body habitus. Limited guidance is available to clinicians on appropriate clinical evaluation in lean individuals with NAFLD, such as for inherited/genetic disorders, lipodystrophy, drug-induced NAFLD, and inflammatory disorders. Emerging data now provide more robust evidence to define the epidemiology, natural history, prognosis, and mortality of lean individuals with NAFLD. Multiple studies have found that NAFLD among lean individuals is associated with increased cardiovascular, liver, and all-cause mortality relative to those without NAFLD. This American Gastroenterological Association Clinical Practice Update provides Best Practice Advice to assist clinicians in evidence-based approaches to the diagnosis, staging, and management of NAFLD in lean individuals.

Methods: This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Lean NAFLD should be diagnosed in individuals with NAFLD and body mass index <25 kg/m2 (non-Asian race) or body mass index <23 kg/m2 (Asian race). BEST PRACTICE ADVICE 2: Lean individuals with NAFLD should be evaluated routinely for comorbid conditions, such as type 2 diabetes mellitus, dyslipidemia, and hypertension. BEST PRACTICE ADVICE 3: Lean individuals with NAFLD should be risk stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis. BEST PRACTICE ADVICE 4: Lean individuals in the general population should not undergo routine screening for NAFLD; however, screening should be considered for individuals older than 40 years with type 2 diabetes mellitus. BEST PRACTICE ADVICE 5: NAFLD should be considered in lean individuals with metabolic diseases (such as type 2 diabetes mellitus, dyslipidemia, and hypertension), elevated liver biochemical tests, or incidentally noted hepatic steatosis. BEST PRACTICE ADVICE 6: Clinicians should query patients routinely regarding alcohol consumption patterns in all patients with lean NAFLD. BEST PRACTICE ADVICE 7: In patients with lean NAFLD, other causes of liver disease should be ruled out, including other causes of fatty liver, such as HIV, lipodystrophy, lysosomal acid lipase deficiency, familial hypobetalipoproteinemia, and medication-induced hepatic steatosis (methotrexate, amiodarone, tamoxifen, and steroids). BEST PRACTICE ADVICE 8: Current evidence is inadequate to support routine testing for genetic variants in patients with lean NAFLD. BEST PRACTICE ADVICE 9: Liver biopsy, as the reference standard, should be considered if there is uncertainty regarding contributing causes of liver injury and/or the stage of liver fibrosis. BEST PRACTICE ADVICE 10: Serum indices (NAFLD fibrosis score and Fibrosis-4 score) and imaging techniques (transient elastography and magnetic resonance elastography) may be used as alternatives to liver biopsy for fibrosis staging and patient follow-up. These tests can be performed at the time of diagnosis and repeated at intervals of 6 months to 2 years, depending on fibrosis stage and the patient's response to intervention. BEST PRACTICE ADVICE 11: If noninvasive tests (eg, Fibrosis-4 and NAFLD fibrosis score) are indeterminate, a second noninvasive test (eg, transient elastography or magnetic resonance elastography) should be performed to confirm the stage and prognosis of NAFLD. BEST PRACTICE ADVICE 12: In lean patients with NAFLD, lifestyle intervention, including exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to target a modest weight loss of 3%-5% is suggested. BEST PRACTICE ADVICE 13: Administration of vitamin E may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis, but without type 2 diabetes mellitus or cirrhosis. Oral pioglitazone 30 mg daily may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis. BEST PRACTICE ADVICE 14: The therapeutic role of glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors in the management of lean NAFLD is not fully defined and requires further investigation. BEST PRACTICE ADVICE 15: Hepatocellular carcinoma surveillance with abdominal ultrasound with or without serum α-fetoprotein twice per year is suggested in patients with lean NAFLD and clinical markers compatible with liver cirrhosis.

Publication types

  • Practice Guideline
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Non-alcoholic Fatty Liver Disease* / diagnosis
  • Non-alcoholic Fatty Liver Disease* / therapy
  • Thinness* / epidemiology