Nonalcoholic Fatty Liver Disease: Common Questions and Answers on Diagnosis and Management


Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease in the United States, affecting up to 30% of adults. There are two forms of NAFLD: nonalcoholic fatty liver (NAFL), defined as 5% or greater hepatic steatosis without hepatocellular injury or fibrosis, and nonalcoholic steatohepatitis (NASH), defined as 5% or greater hepatic steatosis plus hepatocellular injury and inflammation, with or without fibrosis. Individuals with obesity are at highest risk of NAFLD. Other established risk factors include metabolic syndrome and type 2 diabetes mellitus. Although NAFLD is common and typically asymptomatic, screening is not currently recommended, even in high-risk patients. NAFLD should be suspected in patients with elevated liver enzymes or hepatic steatosis on abdominal imaging that are found incidentally. Once other causes, such as excessive alcohol use and hepatotoxic medications, are excluded in these patients, risk scores or elastography tests can be used to identify those who are likely to have fibrosis that will progress to cirrhosis. Liver biopsy should be considered for patients at increased risk of fibrosis and when other liver disorders cannot be excluded with noninvasive tests. Weight loss through diet and exercise is the primary treatment for NAFLD. Other treatments, such as bariatric surgery, vitamin E supplements, and pharmacologic therapy with thiazolidinediones or glucagon-like peptide-1 analogues, have shown potential benefit; however, data are limited, and these therapies are not considered routine treatments. NAFL typically follows an indolent course, whereas patients with NASH are at higher risk of death from cardiovascular disease, cancer, and end-stage liver disease.

Nonalcoholic fatty liver disease (NAFLD) comprises a continuum of fatty liver disease that occurs in the absence of alcohol use or other secondary causes of hepatic steatosis. There are two manifestations of NAFLD (Figure 1).1 One is nonalcoholic fatty liver (NAFL), which is defined as 5% or greater hepatic steatosis without evidence of hepatocellular injury or fibrosis. The other is nonalcoholic steatohepatitis (NASH), which is defined as 5% or greater hepatic steatosis with hepatocellular injury and inflammation, with or without fibrosis.1


It is projected that 100 million people in the United States will have nonalcoholic fatty liver disease by 2030, with direct medical costs of about $103 billion annually.

By 2030, nonalcoholic steatohepatitis is predicted to become the leading indication for liver transplantation in U.S. adults, surpassing hepatitis C.

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Clinical recommendationEvidence ratingComments

Routine screening for NAFLD is not recommended, even for high-risk adults.1


Consensus guidelines; lack of evidence surrounding diagnosis, treatment, and benefit of screening

Patients with hepatic steatosis detected incidentally on imaging who have normal liver enzyme findings and no liver-related symptoms or signs should be assessed for metabolic risk factors (e.g., obesity, diabetes mellitus, dyslipidemia) and alternate causes of hepatic steatosis, such as excessive alcohol consumption or medication use.1,21


Consensus guidelines

Ultrasonography is the imaging test of choice for patients with suspected NAFLD.24,25


Limited-quality disease-oriented evidence

Noninvasive tools such as decision aids (NAFLD Fibrosis Score or Fibrosis-4 Score) or liver stiffness measurements using vibration-controlled elastography or magnetic resonance elastography are clinically useful for identifying patients with NAFLD who have a higher likelihood of developing fibrosis or cirrhosis.1,18,2729,35


Moderate-quality disease-oriented evidence

A liver biopsy should be offered to patients with NAFLD who are at increased risk of nonalcoholic steatohepatitis or advanced fibrosis based on noninvasive testing or if noninvasive testing cannot rule out other possible causes of chronic liver disease.1


Consensus guideline and usual practice

Weight loss through diet and exercise is the primary treatment for NAFLD. A loss of 7% to 10% of total body weight is needed to improve the histopathologic abnormalities in the liver associated with NAFLD.1


Consensus guidelines

There is insufficient evidence to support bariatric surgery, vitamin supplements, thiazolidinediones (pioglitazone [Actos]), and glucagon-like peptide-1 analogues (liraglutide [Victoza]) as first-line/primary treatments for NAFLD.1,6,21,3944,46,48


Low- to high-quality disease-oriented evidence from randomized controlled trials and expert opinion

Statins should be used to treat dyslipidemia in patients with NAFLD.1,21


Consensus guidelines and usual practice

NAFLD = nonalcoholic fatty liver disease.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C =

The Authors

show all author info

ERIN C. WESTFALL, DO, is an assistant professor at the University of Minnesota Medical School Mankato Family Medicine Residency, and is an adjunct assistant professor of family medicine at Mayo Clinic Medical School, Rochester, Minn....

ROBERT JESKE, MD, is an assistant professor at the University of Minnesota Medical School Mankato Family Medicine Residency.

ANDREW R. BADER, DO, is a family physician at Essentia Health–Baxter (Minn.) Clinic.

Address correspondence to Erin C. Westfall, DO, 101 Martin Luther King Jr. Dr., Mankato, MN 56001 (email: Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.


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