Causes of Portal Hypertension
Portal hypertension is classified anatomically into prehepatic, intrahepatic, and posthepatic causes, with cirrhosis from chronic liver disease being the single most common cause overall. 1
Anatomical Classification Framework
The American Association for the Study of Liver Diseases organizes portal hypertension causes by the site of increased resistance to blood flow, which is critical for both diagnosis and management. 1
Prehepatic Causes
These occur before blood reaches the liver:
- Portal vein thrombosis is the most common prehepatic cause 1
- Splenic vein thrombosis 1
- Mesenteric vein obstruction 1
Intrahepatic Causes
These are subdivided into cirrhotic and non-cirrhotic etiologies:
Cirrhotic Causes (Most Common Overall)
Cirrhosis from any chronic liver disease accounts for the majority of portal hypertension cases in Western countries. 1 Specific etiologies include:
- Chronic viral hepatitis B and C 1, 2
- Alcoholic liver disease 1
- Non-alcoholic steatohepatitis (NASH) 1, 2
- Autoimmune hepatitis 1
- Primary biliary cirrhosis (can cause portal hypertension even before established cirrhosis) 1
- Hereditary hemochromatosis 1
- Wilson's disease 1
Non-Cirrhotic Intrahepatic Causes
These represent an important diagnostic pitfall, as patients are often radiologically misclassified as cirrhotic. 2 A key clue is low liver stiffness (<12 kPa) despite signs of portal hypertension. 2
- Idiopathic non-cirrhotic portal hypertension (INCPH) - caused by thrombophilia (40% prevalence), immunological disorders, specific medications, or HIV infection 1, 3, 2
- Schistosomiasis 1, 3
- Congenital hepatic fibrosis 1, 3
- Sarcoidosis 1, 3
- Nodular regenerative hyperplasia 3
Posthepatic Causes
These occur after blood leaves the liver:
- Budd-Chiari syndrome (thrombosis of hepatic veins or inferior vena cava) 1, 3
- Sinusoidal obstruction syndrome (veno-occlusive disease) 1
- Right heart failure 1
Critical Diagnostic Considerations
When to Suspect Non-Cirrhotic Portal Hypertension
Patients typically present with: 3
- Splenomegaly and hypersplenism
- Variceal bleeding
- Normal or near-normal liver function at diagnosis
- Better prognosis than cirrhotic portal hypertension
Essential Diagnostic Steps
Liver biopsy remains essential to exclude cirrhosis in suspected non-cirrhotic portal hypertension. 1, 3 This is a common pitfall—assuming cirrhosis based on imaging alone can lead to misdiagnosis.
Doppler ultrasound is the first-line investigation to assess portal and hepatic vein patency. 3 CT is used for diagnostic confirmation. 3
For INCPH specifically, a thrombophilia workup is necessary since 40% of patients have underlying prothrombotic conditions. 3 Screen for portal vein thrombosis at least every 6 months in these patients. 3
Hemodynamic Pattern Recognition
The hepatic venous pressure gradient (HVPG) measurement pattern differs by etiology. 1 In prehepatic and presinusoidal causes, HVPG remains normal because wedged pressure does not reflect portal pressure—this is a critical diagnostic pitfall. 1
Special Population Considerations
Screening for extrahepatic portal vein obstruction should be considered in patients with myeloproliferative disease and antiphospholipid syndrome. 2 These prothrombotic conditions significantly increase risk.
MR cholangiography should be performed in patients with persistent cholestasis or biliary tract abnormalities suggesting portal biliopathy. 3