Hepatomegaly

Hepatomegaly is an abnormal enlargement of the liver (e.g., liver span > 16 cm in the midclavicular line on ultrasound). Causes are broad and include metabolic (e.g., metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease), infectious (e.g., viral hepatitis), congestive (e.g., right-sided heart failure), neoplastic, and infiltrative conditions. Patients may be asymptomatic or present with features of the underlying disorder (e.g., right upper quadrant discomfort, jaundice, or signs of volume overload). Initial evaluation includes history and physical examination, liver chemistries and liver synthetic function tests, and RUQ ultrasound to assess liver size and parenchymal appearance. Further testing (e.g., viral serologies, iron studies, advanced imaging) is guided by risk factors and initial results, while biopsy is reserved for unclear or high-risk cases. Management focuses on treating the underlying etiology.

• Metabolic ^[1][2]
  • Hemochromatosis
  • Wilson disease
  • Steatotic liver disease
    • Metabolic dysfunction-associated steatotic liver disease (MASLD)
    • Alcohol-associated liver disease: alcohol-associated steatosis, alcohol-associated hepatitis
• Congestive ^[1][2]
  • Right-sided heart failure
  • Constrictive pericarditis
  • Sinusoidal obstruction syndrome
  • Budd-Chiari syndrome
• Neoplastic ^[1][2]
  • Hepatocellular carcinoma (HCC)
  • Metastatic liver disease
  • Benign liver tumors (e.g., hepatic hemangioma, hepatocellular adenoma, focal nodular hyperplasia)
• Hematologic ^[1][2][3]
  • Malignancies (e.g., leukemia, lymphoma, myeloproliferative neoplasms)
  • Hemoglobinopathies (e.g., sickle cell disease, thalassemia)
• Infectious ^[1][2][4]
  • Viral
    • Acute viral hepatitis: A, B, C, E
    • Other viral infections: Epstein-Barr virus, cytomegalovirus, HIV
  • Parasitic (e.g., extraintestinal amebiasis, cystic echinococcosis, fasciola hepatica, schistosomiasis)
  • Bacterial (e.g., pyogenic liver abscess, syphilis, leptospirosis)
  • Mycobacterial (e.g., tuberculosis)
• Inflammatory ^[1]
  • Autoimmune hepatitis
  • Primary biliary cholangitis
  • Primary sclerosing cholangitis
• Infiltrative ^[1][2][3]
  • Amyloidosis
  • Granulomatous diseases (e.g., sarcoidosis)
  • Lysosomal storage diseases (e.g., Gaucher disease)
• Congenital ^[1]
  • Polycystic liver disease
  • Caroli disease

Focused history ^[4][5]

• Right upper quadrant (RUQ) pain
• Constitutional symptoms
• Risk factors for CLD (e.g., long-term unhealthy alcohol use, cardiometabolic risk factors for MASLD)
• Systemic diseases associated with liver disease (e.g., inflammatory bowel disease, hematologic disease)
• Family history of liver disease (e.g., hemochromatosis, Wilson disease)

Focused examination ^[4][5]

• Signs of chronic liver disease
• Pathognomonic signs of a specific chronic liver disease (e.g., Kayser-Fleischer rings in Wilson disease, bronzing of skin in hemochromatosis)
• Lymph node examination
• Abdominal examination
  • Liver percussion: to determine upper and lower margins
  • Liver edge palpation: to assess consistency (e.g., firm or soft) and contour (e.g., smooth or irregular)
  • Associated findings: splenic enlargement, ascites
• Cardiac examination for features of right heart failure

Red flags

• RUQ pain: typical of acute hepatomegaly due to stretching of liver capsule (e.g., acute hepatitis)
• Associated lymphadenopathy and splenomegaly: suggests hematologic malignancy
• Weight loss
• Fever

General principles ^[4][6]

• Confirm clinical suspicion of hepatomegaly with ultrasound examination of the liver.
• Order baseline liver chemistries and liver synthetic function tests.
• Further testing is guided by ultrasound findings and the pattern and severity of liver enzyme abnormalities.
• Liver biopsy may be indicated if routine investigations are inconclusive.

Initial studies

• Liver imaging to confirm hepatomegaly, e.g.: ^[6]
  • Ultrasound (first-line)
  • CT and/or MRI
• Baseline laboratory studies ^[4][5]
  • Liver chemistries
  • Liver synthetic function tests

Additional studies ^[4][5]

Laboratory studies

Consider the following studies to investigate the suspected etiology:

• Viral hepatitis panel
• Lipid panel and hyperglycemia tests to identify cardiometabolic risk factors for MASLD
• Serology for type 1 autoimmune hepatitis
• See also:
  • "Diagnostics for chronic liver disease"
  • "Diagnostics in elevated transaminases"
  • "Diagnostics for cholestasis"

Imaging

The choice of additional imaging is based on liver ultrasound findings, e.g.:

• Doppler ultrasound for suspected outflow obstruction (e.g., Budd-Chiari syndrome)
• Transthoracic echocardiogram for suspected right heart failure
• Multiphase CT/MRI to evaluate focal lesions suggestive of HCC

• Anatomical variants (e.g., Riedel lobe) ^[15]
• Apparent hepatomegaly due to downward displacement of the liver (e.g., due to COPD or a right pleural effusion)