Basics

Description

Hepatomegaly is enlargement of the liver beyond age-adjusted normal values. It can be due to intrinsic liver disease or associated with systemic diseases seen in infants and children.

  • Normal liver size
    • Depends on age, gender, and body size
    • Average liver span is 4.5 to 5 cm (neonates), 6 to 6.5 cm (12-year-old girls), 7 to 8 cm (12-year-old boys), and up to 16 cm (adults).

Risk Factors

  • Cardiac disease
  • Metabolic disorders

Pathophysiology

  • Inflammation (hepatitis)
  • Excessive storage
  • Infiltration
  • Vascular congestion
  • Biliary obstruction

Etiology

  • Inflammation (hepatitis)
    • Infections
      • Viral infections
        • Hepatitis types A to E
        • Epstein-Barr virus (EBV)
        • Cytomegalovirus (CMV)
        • Coxsackievirus
      • Congenital infections
      • Bacterial infections
        • Hepatic abscess
        • Tuberculosis
        • Sepsis
      • Parasitic infections
        • Amebiasis
        • Flukes
        • Schistosomiasis
        • Malaria
      • Fungal diseases
        • Candidiasis
        • Histoplasmosis
      • STDs
        • Gonococcal perihepatitis
        • Syphilis
        • HIV
      • Zoonotic diseases
        • Brucellosis
        • Leptospirosis
        • Bartonella henselae
        • Pasteurella multocida
    • Toxic, metabolic, drugs
      • Acetaminophen
      • Alcohol
      • Corticosteroids
      • Erythromycin
      • Hypervitaminosis A
      • Iron
      • Isoniazid
      • Nitrofurantoin
      • Oral contraceptives
      • Phenobarbital
      • Valproate
    • Autoimmune
      • Autoimmune hepatitis
      • Sarcoidosis
      • Systemic lupus erythematosus
  • Storage disorders
    • Glycogen
      • Glycogen storage disease
      • Diabetes mellitus
      • Total parenteral nutrition (TPN)
    • Lipids
      • Wolman disease
      • Niemann-Pick disease
      • Gaucher disease
    • Fat
      • Nonalcoholic fatty liver disease
      • Cystic fibrosis
      • Fatty acid oxidation defect
      • Mucopolysaccharidoses
      • Reye syndrome
    • Iron
      • Hemochromatosis
    • Copper
      • Wilson disease
    • Abnormal proteins
      • α1-Antitrypsin deficiency
  • Infiltration
    • Tumors
      • Benign tumors
        • Hemangioma
        • Hemangioendothelioma
        • Mesenchymal hamartoma
        • Focal nodular hyperplasia
        • Adenoma
      • Malignant tumors
        • Hepatoblastoma
        • Hepatocellular carcinoma
      • Metastatic tumors
        • Leukemia
        • Lymphoma
        • Neuroblastoma
        • Wilms tumor
        • Histiocytosis
    • Cysts
      • Choledochal cysts
      • Parasitic cysts
      • Polycystic liver disease
    • Amyloidosis
    • Granulomatous disease
    • Hemophagocytic syndromes
    • Extramedullary hematopoiesis
  • Vascular congestion
    • Intrahepatic
      • Veno-occlusive disease
      • Budd-Chiari syndrome (hepatic vein thrombosis)
    • Suprahepatic
      • Congestive heart failure (CHF)
      • Pericardial disease
      • Suprahepatic web
  • Biliary obstruction
    • Biliary atresia
    • Alagille syndrome
    • Choledochal cyst
    • Cholelithiasis
    • Tumors
    • Primary sclerosing cholangitis

Diagnosis

History

Obtain a detailed history to identify potential risk factors for liver disease and to evaluate for underlying systemic disease.

  • Question: Prenatal history suggesting possible congenital infection or HIV infection?
  • Significance: Infections may cause hepatomegaly.
  • Question: Prolonged hyperbilirubinemia after 2 weeks of age?
  • Significance: Could suggest biliary atresia, cystic fibrosis, α1-antitrypsin deficiency
  • Question: Developmental delay or poor growth?
  • Significance: Could suggest a metabolic disorder
  • Question: Age of onset?
  • Significance: Early age could suggest congenital infection or metabolic disorder.
  • Question: Family history of early infant death or hepatic, neurodegenerative, or psychiatric disease?
  • Significance: Could suggest a metabolic disorder
  • Question: Sexual activity, IV drug use, tattoo?
  • Significance: Risk factors for hepatitis B and C infections and HIV; also consider gonococcal perihepatitis (Fitz-Hugh–Curtis syndrome) and syphilis.
  • Question: Foreign travel?
  • Significance: Parasitic infection or liver abscess
  • Question: Pruritus?
  • Significance: Can be a subtle sign of cholestasis
  • Question: Contaminated shellfish?
  • Significance: Source of large outbreaks of hepatitis A
  • Question: Previous TPN?
  • Significance: Can lead to cholestasis, bile duct proliferation, fatty infiltration, and early cirrhosis
  • Question: Medications, supplements, and recreational drug use?
  • Significance: Many commonly used medications can be hepatotoxic; ask about vitamin A, alcohol, and certain mushroom species.
  • Question: Other chronic illnesses?
  • Significance:
    • Heart disease: liver enlargement from CHF
    • Cystic fibrosis: related liver disease
    • Diabetes mellitus: increased glycogen secretion
    • Severe anemia: extramedullary hematopoiesis
    • Inflammatory bowel disease: increased likelihood of primary sclerosing cholangitis
    • Obesity: nonalcoholic fatty liver disease

Physical Exam

Perform a careful physical exam to look for clues to etiology and for signs of chronic liver disease.

  • Finding: Liver edge?
  • Significance:
    • Children <2 years: can be normal up to 3.5 cm below costal margin; however, if >2 cm, further workup or referral may be indicated.
    • Children >2 years: normal up to 2 cm
    • Verify all suspected cases of hepatomegaly by checking the liver span.
  • Finding: Signs of chronic liver disease?
  • Significance:
    • Liver is usually firm and enlarged; can decrease in size with advanced disease
    • Splenomegaly, ascites, caput medusae, spider angiomas, esophageal varices, and hemorrhoids suggest portal hypertension.
    • Also look for signs of occult bleeding or bruising due to vitamin K deficiency.
  • Finding: Tender liver?
  • Significance: May indicate hepatitis or acutely congested liver secondary to right-sided heart failure or Budd-Chiari syndrome
  • Finding: Splenomegaly?
  • Significance:
    • In the context of chronic liver disease, implies portal hypertension
    • In the context of other signs of viral illness, suggests acute viral hepatitis
    • In the absence of these signs, suggests storage disease or malignancy
  • Finding: Coarse facial features?
  • Significance: Suggests mucopolysaccharidoses
  • Finding: Kayser-Fleischer rings or cataracts?
  • Significance: Suspect Wilson disease

Differential Diagnosis

  • Normal anatomic variations of the liver may be confused with hepatomegaly.
    • Riedel lobe: an extended, tongue-like, right lobe of the liver
    • Beaver tail liver: Large left hepatic lobe extends laterally to contact and surround the spleen.
  • Disorders that result in the liver being displaced caudally into the abdomen may result in physical findings that are mistaken for hepatomegaly.
    • Pulmonary hyperinflation
    • Right pleural effusion
    • Congenital diaphragmatic hernia
    • Subdiaphragmatic abscesses
    • Retroperitoneal mass lesions
    • Scoliosis
    • Rib cage anomalies

Diagnostic Tests and Interpretation

Initial tests: All patients with hepatomegaly should have a laboratory evaluation. History and physical exam should direct laboratory and further testing.

Initial Tests

  • CBC with differential
    • Thrombocytopenia may suggest portal hypertension.
  • Comprehensive metabolic panel
    • Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) can reflect the amount of damage to hepatocytes. Elevations >1,000 IU/L indicate severe damage. ALT is more liver-specific.
    • Albumin assesses synthetic function.
    • Hyperbilirubinemia suggests cholestasis (direct hyperbilirubinemia) or hemolytic disease (indirect hyperbilirubinemia).
  • Prothrombin time (PT)
    • Assesses synthetic function
    • Prolongation can occur with an acute injury or illness.
    • Can also be prolonged due to vitamin K deficiency
  • γ-glutamyl transferase (GGT) and alkaline phosphatase
    • Elevation of GGT out of proportion to elevation in aminotransferases can indicate an obstructive or infiltrative process.
    • If an elevated GGT is associated with elevations in bilirubin, cholesterol, and alkaline phosphatase, an obstructive process is more likely.
  • Ammonia level
    • Important to send on ice
    • Increasing ammonia levels, with prolonged PT, can suggest liver failure.
  • Viral hepatitis serology
    • Hepatitis A IgM, hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody, hepatitis C antibody
    • Should be obtained in patients with suggestive prodromal illness
  • EBV and CMV IgM/IgG
  • Monospot
    • Nonspecific heterophile antibody test for EBV infection; can be predictive in association with an elevation of atypical lymphocytes
    • High false-negative rate in children <4 years
  • α-Fetoprotein and carcinoembryonic antigen
    • Tumor markers for hepatoblastoma and hepatocellular carcinoma, respectively
  • “TORCH” titers
    • Consider toxoplasmosis, syphilis, rubella, CMV, and HIV.
    • Consider in newborns with hepatomegaly.
  • Autoimmune markers
    • Serum immunoglobulins, antinuclear antibody, anti–smooth muscle antibody, anti-liver/kidney microsomal antibody, soluble liver antigen
  • Ceruloplasmin and urinary copper excretion
    • Wilson disease: decreased ceruloplasmin and increased urinary copper excretion
    • Consider for patients with unexplained liver disease and neurologic symptoms.
  • Iron, total iron-binding capacity (TIBC), ferritin
    • To assess for hemochromatosis
  • α1-Antitrypsin phenotype
    • To look for α1-antitrypsin deficiency
    • Only send if no blood transfusion in last month
  • Abdominal ultrasound with Doppler
    • Most helpful initial study
    • Perform in all patients with acholic stools, asymmetric liver enlargement or mass.
    • Can measure liver size and consistency, masses, cysts, abscesses, biliary tree abnormalities, and venous blood flow
  • CT or MRI can be done for further evaluation.
  • Echocardiogram to assess heart function
  • Liver biopsy is often needed for definitive diagnosis.
ALERT
Indications for immediate hospitalization:
  • Persistent anorexia and vomiting
  • Mental status changes
  • Worsening jaundice
  • Relapse of symptoms after initial improvement
  • Known exposure to a liver toxin
  • Rising PT/INR
  • Rising ammonia level
  • Bilirubin >20 mg/dL
  • AST >2,000 IU/L
  • Development of new ascites
  • Hypoglycemia
  • Leukocytosis and thrombocytopenia
  • Hematemesis

Treatment

Depends on underlying etiology of hepatomegaly

ALERT
Refer to gastroenterologist or hepatologist if
  • Unexplained or persistent elevation of liver enzymes
  • Decreased synthetic function or signs of portal hypertension

Additional Reading

  1. Clayton PT. Diagnosis of inherited disorders of liver metabolism. J Inherit Metab Dis. 2003;26(2–3):135–146.  [PMID:12889656]
  2. Clemente M, Schwarz K. Hepatitis: general principles. Pediatr Rev. 2011;32(8):333–340.  [PMID:21807874]
  3. Diehl-Jones WL, Askin DF. The neonatal liver part II: assessment and diagnosis of liver dysfunction. Neonatal Netw. 2003;22(2):7–15.  [PMID:12696721]
  4. Fishbein M, Mogren J, Mogren C, et al. Undetected hepatomegaly in obese children by primary care physicians: a pitfall in the diagnosis of pediatric nonalcoholic fatty liver disease. Clin Pediatr (Phila). 2005;44(2):135–141.  [PMID:15735831]
  5. Wolf AD, Lavine JE. Hepatomegaly in neonates and children. Pediatr Rev. 2000;21(9):303–310.  [PMID:10970452]

Codes

ICD-9

  • 789.1 Hepatomegaly
  • 070.9 Unspecified viral hepatitis without mention of hepatic coma
  • 573.0 Chronic passive congestion of liver
  • 576.2 Obstruction of bile duct

ICD-10

  • R16.0 Hepatomegaly, not elsewhere classified
  • B19.9 Unspecified viral hepatitis without hepatic coma
  • K76.1 Chronic passive congestion of liver
  • K83.1 Obstruction of bile duct

SNOMED

  • 80515008 Large liver (disorder)
  • 3738000 Viral hepatitis (disorder)
  • 76281005 Hepatic congestion
  • 235918000 Obstruction of biliary tree (disorder)

FAQ

  • Q: Why does cholestasis cause pruritus?
  • A: This phenomenon probably reflects an abnormal accumulation of bile acids in the skin.
  • Q: Do patients with chronic liver disease have any different nutritional needs?
  • A: Yes. Patients may have impaired fat absorption and therefore may have deficiencies of fat-soluble vitamins A, D, E, and K, which can lead to visual disturbances, rickets, pathologic fractures, neuropathy, hemolytic anemia, or bleeding. Consider supplementing the diet with medium-chain triglycerides, which are more easily absorbed.
  • Q: What causes TPN-associated cholestasis?
  • A: It is likely multifactorial. TPN components act as toxins; bacterial endotoxins and lack of enteral feeding also play significant roles.
  • Q: How is liver span determined by physical exam?
  • A: Measure the distance between the upper edge, determined by percussion, and the lower edge, determined by percussion, palpation, or auscultation in the midclavicular line. Can use the “scratch test”: with the stethoscope placed below the xiphoid, the examiner should gently scratch superiorly, starting in from the right lower quadrant, and listen for sound enhancement as the finger passes over the liver edge.

Authors

Sivan Kinberg, MD, MS, MA

Sarah S. Lusman, MD, PhD


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TY - ELEC T1 - Hepatomegaly ID - 617223 ED - Cabana,Michael D, BT - 5-Minute Pediatric Consult UR - https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617223/all/Hepatomegaly PB - Wolters Kluwer ET - 8 DB - Pediatrics Central DP - Unbound Medicine ER -