What are the common causes of hepatomegaly and their treatments?

Common Causes of Hepatomegaly

The two most common causes of hepatomegaly are nonalcoholic fatty liver disease (NAFLD) and alcohol-induced liver disease. 1

Primary Causes of Hepatomegaly

1. Nonalcoholic Fatty Liver Disease (NAFLD)

• Epidemiology: Most common liver disease in developed countries with prevalence of 20-30% in general population, increasing to 70% with obesity and 90% with diabetes 1
• Pathophysiology: Spectrum ranging from simple steatosis (70-75% of cases) to nonalcoholic steatohepatitis (NASH) with inflammation (25-30% of cases) 1
• Diagnosis:
  • Ultrasound is first-line investigation with 84.8% sensitivity and 93.6% specificity for moderate/severe steatosis 1
  • Sensitivity decreases to 53-65% for mild steatosis 1
  • Characterized by increased liver echogenicity on ultrasound 1
• Risk factors: Metabolic syndrome, obesity, diabetes mellitus, dyslipidemia 1

2. Alcohol-Induced Liver Disease

• Pathophysiology: Excessive alcohol intake leads to fatty infiltration, inflammation, and potential progression to fibrosis/cirrhosis 1
• Laboratory findings: AST:ALT ratio generally >2 (compared to <1 in metabolic-related fatty liver) 1
• Diagnosis: Requires accurate history of alcohol consumption and exclusion of other causes 1

Secondary Causes of Hepatomegaly

3. Viral Hepatitis

• Hepatitis B and C: Can cause hepatomegaly with elevated transaminases 1, 2
• Hepatitis C: Steatosis present in almost 50% of HCV patients, particularly genotype 3 2

4. Metabolic/Genetic Disorders

• Glycogen Storage Diseases: Characterized by glycogen accumulation in hepatocytes 1, 3
• Hemochromatosis: Iron overload disorder that can cause hepatomegaly 1
• Wilson's Disease: Copper accumulation disorder 1
• Lysosomal Storage Diseases: Rare group of disorders with collective incidence of 1:5000 live births 4

5. Vascular Disorders

• Budd-Chiari Syndrome: Hepatic vein thrombosis presenting with hepatomegaly, abdominal pain, and ascites 1
• Congestive Heart Failure: Can cause "shock liver" with hepatomegaly 1

6. Malignant Infiltration

• Primary liver cancer: Hepatocellular carcinoma can present with hepatomegaly 1
• Metastatic disease: Breast cancer, small cell lung cancer, lymphoma, and melanoma can infiltrate liver 1

Diagnostic Approach

1. Initial evaluation:

   • Complete history including alcohol consumption, medications, and metabolic risk factors
   • Laboratory tests: Liver enzymes, viral hepatitis serologies, metabolic panel
   • Imaging: Ultrasound as first-line investigation 1

2. Further workup:

   • For unexplained hepatomegaly, consider screening for:
     • Hepatitis C infection
     • Thyroid dysfunction
     • Drug-induced liver injury
     • Wilson's disease
     • Hemochromatosis
     • Celiac disease
     • Lipid metabolism disorders 5

3. Advanced imaging:

   • CT or MRI may be needed for better characterization of liver lesions 6
   • Liver biopsy may be considered when etiology remains unclear 1

Clinical Pearls and Pitfalls

• Important distinction: Steatosis may progress to fibrosis and cirrhosis, while glycogenosis (in diabetic patients) is reversible with improved glycemic control 3
• Medication-induced hepatomegaly: Consider nucleoside analogs (in HIV patients), amiodarone, methotrexate, tamoxifen, and corticosteroids as potential causes 7, 1
• Avoid missing malignant infiltration: Consider underlying malignancy in patients with massive hepatomegaly or previous cancer history 1
• Genetic factors: Polymorphisms in genes like PNPLA3, TM6SF2, and MBOAT7 may promote development and progression of fatty liver disease regardless of underlying etiology 5

By recognizing these common causes of hepatomegaly and following a systematic diagnostic approach, clinicians can identify the underlying etiology and implement appropriate management strategies to prevent disease progression.