What is the appropriate workup for hepatomegaly (enlarged liver)?

From the Guidelines

The workup for hepatomegaly should begin with a thorough history and physical examination, followed by laboratory tests including liver function tests (ALT, AST, alkaline phosphatase, bilirubin), complete blood count, and coagulation studies, and initial imaging should include an abdominal ultrasound to confirm hepatomegaly and assess for structural abnormalities, as recommended by the most recent guidelines 1. The initial evaluation should be guided by the patient's clinical presentation and risk factors.

• Laboratory tests should include liver function tests, complete blood count, and coagulation studies.
• Initial imaging should include an abdominal ultrasound to confirm hepatomegaly and assess for structural abnormalities.
• Additional testing should be guided by clinical suspicion and may include viral hepatitis serologies (hepatitis A, B, C), iron studies, ceruloplasmin, alpha-1 antitrypsin levels, and autoimmune markers like ANA and anti-smooth muscle antibodies.
• For patients with risk factors for fatty liver disease, lipid panels and hemoglobin A1c should be checked.
• If the diagnosis remains unclear after initial testing, advanced imaging such as CT or MRI may be warranted, as suggested by the guidelines 1. In cases where structural abnormalities or masses are identified, a liver biopsy might be necessary for definitive diagnosis, although this should be discussed by a multidisciplinary team, including a hepatobiliary and transplant surgeon, as recommended by the guidelines 1. The workup should be tailored to the patient's clinical presentation, as hepatomegaly can result from various etiologies including viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, hemochromatosis, autoimmune hepatitis, and malignancy, and early identification of the underlying cause is crucial for implementing appropriate treatment and preventing progression to cirrhosis or liver failure, as emphasized by the guidelines 1.

From the Research

Hepatomegaly Workup

• Hepatomegaly, or enlargement of the liver, can be caused by various conditions, including hepatocellular injury and cholestatic injury 2.
• The evaluation of hepatomegaly typically involves liver biochemical tests, including aminotransferases, alkaline phosphatase, gamma-glutamyl transferase, bilirubin, albumin, prothrombin time, and international normalized ratio (INR) 3.
• Abnormal liver biochemical tests can be categorized based on the pattern and magnitude of aminotransferase elevation, with hepatocellular pattern causes including non-alcoholic fatty liver disease, alcohol use, and chronic viral hepatitis, and cholestatic pattern causes including biliary pathology and other conditions with hyperbilirubinemia 3.

Diagnostic Evaluation

• A systematic, stepwise approach to the evaluation and management of abnormal liver test results is recommended to optimize high-value care 4.
• The pattern and severity of liver injury may provide clues about the cause of disease and should guide diagnostic evaluation with serologic testing and liver imaging 4.
• Testing for viral hepatitis, nonalcoholic fatty liver disease, alcoholic liver disease, hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency may be undertaken as part of the evaluation of hepatocellular injury 2.
• For the evaluation of an alkaline phosphatase elevation determined to be of hepatic origin, testing for primary biliary cholangitis and primary sclerosing cholangitis should be undertaken 2.

Laboratory Tests

• Liver biochemical tests, including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin, should be interpreted in the context of a patient's history and examination 2, 3.
• Elevated total serum bilirubin levels should be fractionated to direct and indirect bilirubin fractions, and an elevated serum conjugated bilirubin implies hepatocellular disease or biliary obstruction in most settings 2.
• A liver biopsy may be considered when serologic testing and imaging fail to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 2.

Note: The study from 1976 5 is not relevant to the topic of hepatomegaly workup.