eMedicine Specialties > Gastroenterology > Liver

Fatty Liver: Differential Diagnoses & Workup

Author: Dawn Sears, MD, Assistant Professor of Internal Medicine, Division of Gastroenterology and Hepatology, Scott and White Memorial Hospital
Contributor Information and Disclosures

Updated: Jan 6, 2009

Differential Diagnoses

Alcoholic Fatty Liver
Hepatitis D
Alcoholic Hepatitis
Hepatitis E
Alcoholism
Hepatitis, Viral
Alpha1-Antitrypsin Deficiency
Hyperthyroidism
Autoimmune Hepatitis
Hypothyroidism
Celiac Sprue
Isoniazid Hepatotoxicity
Cirrhosis
Malabsorption
Drug-Induced Hepatotoxicity
Primary Biliary Cirrhosis
Hemochromatosis
Primary Sclerosing Cholangitis
Hepatitis A
Protein-Losing Enteropathy
Hepatitis B
Vitamin A Toxicity
Hepatitis C
Wilson Disease

Other Problems to Be Considered

The differential diagnosis is broad. The diagnosis of steatohepatitis requires the exclusion of many factors, including drugs, such as amiodarone, perhexiline maleate, methotrexate, corticosteroids, and estrogens. A diagnosis of NASH can be established only when alcohol excess (>10 g/d) can be excluded. Acute fatty liver can occur during pregnancy and likely results from maternal-fetal interactions related to genetic abnormalities in mitochondrial beta-oxidation of fatty acids.

Workup

Laboratory Studies

  • No laboratory studies can help definitively establish a diagnosis of fatty liver or NASH.
  • Aminotransferases
    • The only abnormality may be an elevated aspartate aminotransferase (AST) or ALT level. These levels may be elevated as much as 10-fold. However, the AST and ALT levels may be normal in some patients with fatty liver or NASH.
    • In the absence of cirrhosis, an AST-to-ALT ratio of greater than 2 suggests alcohol use, whereas a ratio of less than 1 may occur in patients with NASH.
  • Alkaline phosphatase
    • This level can be elevated in some patients with NASH.
    • Usually, it is less than 2- to 3-times normal.
  • Lipids
    • Hyperlipidemia may be present.
    • Increased triglycerides are common in children and in patients with metabolic syndrome.
  • Iron studies
    • Elevations in serum ferritin, iron, and/or decreased transferrin saturation may occur in patients with NASH.
    • Although iron overload occurs in a small proportion of patients with NASH, these patients have more severe disease. An iron index score may be ordered on a liver biopsy specimen to evaluate for phlebotomy. Hemochromatosis gene testing is recommended when the ferritin is significantly elevated. Simply eliminating dietary iron has been shown to improve fatty liver.
  • Viral serological markers: Before a diagnosis of NASH can be made, viral markers should be tested and viral infection excluded.
  • Autoimmune markers, such as antinuclear antibody (ANA) and anti–smooth muscle antibody (ASMA), are often slightly elevated in NASH.
    • Positive antibodies are associated with more severe fibrosis levels.
    • In the appropriate clinical setting, serum protein electrophoresis (SPEP) and anti–liver-kidney antibody may lead to a diagnosis of autoimmune liver disease.
  • Fasting insulin and glucose levels will alert the clinician to potential glucose intolerance and may lead to more effective therapies.

Imaging Studies

  • Ultrasound
    • The liver is hyperechogenic or bright.
    • Steatosis is detected only when substantial (30% or more) fatty change is present.
    • Studies in patients who are about to undergo gastric bypass surgery reveal a 93% predictive value of NASH, with an accuracy of 76%.
  • Computed tomography
    • The mean CT (Hounsfield unit) number is lower in the liver than in the spleen.
    • CT scans may be used to monitor the course of the disease on successive scans.
    • Focal fatty lesions may be identified by dual-energy CT scans that demonstrate increased attenuation with increasing energy and no change in normals.
  • Magnetic resonance imaging
    • MRI may be useful for excluding fatty infiltration. Phase-contrast imaging correlates with the quantitative assessment of fatty infiltration across the entire range of liver disease.
    • Loss of intensity on T1-weighted images may be useful in identifying focal fat.
  • Noninvasive studies, such as ultrasound, CT scan, and MRI, may identify the presence of a fatty liver. However, these imaging techniques cannot distinguish between benign steatosis and steatohepatitis. Benign steatosis may be focal or diffuse, whereas steatohepatitis is usually diffuse.

Other Tests

  • Since fatty liver is common in the Western world and since NASH carries a 10% risk of cirrhosis, a simple blood test predictive of which patients would have worse disease is desirable. This has led to studies of databases, rat models, scoring systems, prospective studies, and novel uses for old markers of inflammation and scarring.8,9,10,11,2
  • The easily obtained NAFLD fibrosis score that consists of age, hyperglycemia, BMI, platelet count, albumin and AST/ALT ratio appears easy to use and promising to avoid excessive liver biopsies.12
  • Other noninvasive commercial tests for fibrosis (eg, FIBROSpect, FibroSURE, FibroScan) have not yet been proven in the Western population for NASH; however, large studies are ongoing.

Procedures

  • Liver biopsy
    • A liver biopsy and histopathologic examination are required to establish the diagnosis.
    • The diagnosis should be considered in all patients with unexplained elevations in serum aminotransferases (eg, with findings negative for viral markers or autoantibodies or with no history of alcohol use).
    • The Brunt classification is the standard used to report NAFLD and NASH biopsy specimens.13

Histologic Findings

The diagnosis of fatty liver or NASH can be established only with a liver biopsy. Specific histologic findings include the following: (1) steatosis, which usually is macrovesicular but may be microvesicular or mixed; (2) inflammatory infiltrates consist of mixed neutrophilic and mononuclear cells, and portal infiltrates usually are not seen (unlike in hepatitis C); (3) ballooning degeneration; and (4) fibrosis. The first 3 findings are used to calculate the NAFLD activity score (0-8).

Staging

The stage of disease is determined by the NAFLD activity score and the amount of fibrosis.

More on Fatty Liver

Overview: Fatty Liver
Differential Diagnoses & Workup: Fatty Liver
Treatment & Medication: Fatty Liver
Follow-up: Fatty Liver
References
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References

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Further Reading

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Keywords

fatty liver, fatty liver disease, steatosis, hepatic steatosis, steatohepatitis, alcohol-related fatty liver, alcoholic steatohepatitis, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, NASH, liver fibrosis, cirrhosis, hyperlipidemia, protein-calorie malnutrition, abetalipoproteinemia, galactosemia, glycogen storage disorder, hereditary fructose intolerance, homocystinuria, hypobetalipoproteinemia, Refsum disease, systemic carnitine deficiency, tyrosinemia, Weber-Christian disease, Wilson disease, variceal bleeding, encephalopathy, starvation,jejunoileal bypass, total parenteral nutrition, rapid weight loss

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Contributor Information and Disclosures

Author

Dawn Sears, MD, Assistant Professor of Internal Medicine, Division of Gastroenterology and Hepatology, Scott and White Memorial Hospital
Disclosure: Nothing to disclose.

Medical Editor

John Gunn Lee, MD, Director of Pancreaticobiliary Service, Associate Professor, Department of Internal Medicine, Division of Gastroenterology, University of California at Irvine School of Medicine
John Gunn Lee, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Simmy Bank, MD, Chair, Professor, Department of Internal Medicine, Division of Gastroenterology, Long Island Jewish Hospital, Albert Einstein College of Medicine
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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