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Overscreening Leads to Overdiagnosis of MASLD

Metabolic Dysfunction–Associated Steatotic Liver Disease: Diagnosis and Management

Smriti Ohri, MD
Emily Waterman, MD, MPH
Ana R. Quiñones, PhD

American Family Physician. 2026;113(6):578-585.

Author disclosure: No relevant financial relationships.

This clinical content conforms to AAFP criteria for CME.

Metabolic dysfunction–associated steatotic liver disease (MASLD; formerly nonalcoholic fatty liver disease) is an increasingly common cause of chronic liver disease. It is fatty infiltration of the liver with at least one cardiometabolic risk factor, without a secondary cause and no or low alcohol use. People with MASLD and other risk factors (eg, diabetes, obesity) are at higher risk for long-term adverse outcomes, including cirrhosis and hepatocellular carcinoma. Screening for advanced fibrosis involves two-step sequential noninvasive testing. Clinicians should risk stratify using the Fibrosis-4 index. Secondary risk assessment with vibration-controlled transient elastography or ultrasound-based methods is needed in people with indeterminate or high-risk Fibrosis-4 scores. Monitoring and management of earlier stages of the MASLD spectrum in primary care may reduce the risk of adverse outcomes and maximize care before specialist referral. Patients should be counseled on lifestyle interventions (eg, at least 5% weight loss for people with overweight or obesity, healthy diet, at least 150 minutes of moderate aerobic physical activity per week) to improve steatosis and lower cardiovascular risk. Additional lifestyle recommendations include smoking cessation, limited alcohol intake in people with no or mild fibrosis, and no alcohol for those with more significant fibrosis. Semaglutide and resmetirom are approved by the US Food and Drug Administration for treatment of metabolic dysfunction–associated steatohepatitis in patients with moderate or severe fibrosis.

Metabolic dysfunction–associated steatotic liver disease (MASLD), formerly called nonalcoholic fatty liver disease, is fatty infiltration of the liver with at least one of five cardiometabolic risk factors (Table 1), without a secondary cause and no or low alcohol use (fewer than three to four drinks per day for men or two to three drinks per day for women).1 Recognition of MASLD has improved, and management now emphasizes preventing cardiovascular disease, addressing cardiometabolic risk factors, and mitigating fibrosis progression. The terminology changed in 2023 after a modified Delphi process recommended using nonstigmatizing language reflecting the disease pathogenesis, opting for metabolic dysfunction and steatotic instead of nonalcoholic and fatty, respectively. The process involved international liver associations, clinicians, and patient advocates.2,3

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation Evidence rating Comments
Screening using the Fibrosis-4 index is recommended for patients at high risk for advanced fibrosis.1,4,12,16 C Expert opinion and consensus guidelines
Prevention of cardiovascular disease and management of cardiometabolic risk factors with current standards of care are recommended for people with MASLD.4,16 C High-quality, long-term cohort studies, surveillance data, and consensus guidelines
Nonpharmacologic treatment of MASLD includes at least 5% weight loss in people with overweight or obesity, healthy diet, and at least 150 minutes of moderate aerobic activity per week, although any increase in physical activity is beneficial.1,4,12,16,22–25,27,33,34 B Systematic reviews, meta-analyses, and consensus guidelines
Combined with lifestyle interventions, semaglutide is recommended to treat MASLD in adults with moderate (F2) to severe (F3) fibrosis.42,46,47 C Randomized controlled trial with disease-oriented outcomes
Along with diet and exercise, resmetirom is recommended in adults with noncirrhotic MASH with moderate to severe fibrosis.45 C Randomized controlled trial with disease-oriented outcomes

MASH = metabolic dysfunction–associated steatohepatitis; MASLD = metabolic dysfunction–associated steatotic liver disease.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

SMRITI OHRI, MD, FAAFP, is an associate professor at Oregon Health & Science University, Portland.

EMILY WATERMAN, MD, MPH, is an associate professor at Oregon Health & Science University, Portland.

ANA R. QUIÑONES, PhD, FGSA, is a professor at Oregon Health & Science University, Portland.

Address correspondence to Ana R. Quiñones, PhD, at quinones@ohsu.edu.

Author disclosure: No relevant financial relationships.

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