Abstract

Objective

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.

Methods

The American Association of Clinical Endocrinology conducted literature searches for relevant articles published from January 1, 2010, to November 15, 2021. A task force of medical experts developed evidence-based guideline recommendations based on a review of clinical evidence, expertise, and informal consensus, according to established American Association of Clinical Endocrinology protocol for guideline development.

Recommendation Summary

This guideline includes 34 evidence-based clinical practice recommendations for the diagnosis and management of persons with NAFLD and/or NASH and contains 385 citations that inform the evidence base.

Conclusion

NAFLD is a major public health problem that will only worsen in the future, as it is closely linked to the epidemics of obesity and type 2 diabetes mellitus. Given this link, endocrinologists and primary care physicians are in an ideal position to identify persons at risk on to prevent the development of cirrhosis and comorbidities. While no U.S. Food and Drug Administration-approved medications to treat NAFLD are currently available, management can include lifestyle changes that promote an energy deficit leading to weight loss; consideration of weight loss medications, particularly glucagon-like peptide-1 receptor agonists; and bariatric surgery, for persons who have obesity, as well as some diabetes medications, such as pioglitazone and glucagon-like peptide-1 receptor agonists, for those with type 2 diabetes mellitus and NASH. Management should also promote cardiometabolic health and reduce the increased cardiovascular risk associated with this complex disease.

Conclusions

Endocrinologists and primary care clinicians are in an ideal position to identify those at risk early on to prevent the development of cirrhosis and comorbidities. Screening should involve calculation of the individual’s liver fibrosis risk (FIB-4), followed by additional plasma biomarkers and/or liver imaging based on fibrosis risk stratification into low, indeterminate, or high risk of developing future cirrhosis, with referral to a liver specialist for those in the higher-risk groups. Lifestyle changes leading to an energy deficit if overweight or obese and improved cardiometabolic health are essential to reduce CVD risk. Treatment must include consideration of weight-loss medications, particularly GLP-1 RAs with proven benefit for steatohepatitis and bariatric surgery. Some diabetes medications, such as pioglitazone and GLP-1 RAs, should be preferred for those with T2D and NASH, particularly when at indeterminate or high risk of developing future cirrhosis. Management should also include careful control of CV risk factors, such as hypertension and atherogenic dyslipidemia. Pediatric NAFLD is also becoming a growing concern, but there is limited awareness among health care professionals about the problem. Inadequate evidence in terms of the optimal diagnostic and treatment pathways is a major barrier with current care being based on early diagnosis and promotion of healthy lifestyle changes. Rapid changes in diagnostic tools and in drug development promise to offer new options for endocrinologists and other health care professionals involved in the management of NAFLD.