What are the causes of portal hypertension?

Causes of Portal Hypertension

Portal hypertension develops from increased resistance to portal blood flow, with cirrhosis from chronic liver disease being the predominant cause, accounting for the majority of cases. 1

Anatomical Classification of Causes

Portal hypertension is classified by the site of increased resistance to blood flow into three main categories 2, 3:

Prehepatic Causes

• Portal vein thrombosis - the most common prehepatic cause 3
• Splenic vein thrombosis 2

Intrahepatic Causes

Cirrhotic (Sinusoidal):

• Cirrhosis from any chronic liver disease - this is the single most common cause overall 1
• Chronic viral hepatitis B/C 2
• Alcoholic liver disease 2
• Non-alcoholic steatohepatitis (NASH) 2
• Autoimmune hepatitis 2
• Primary biliary cirrhosis (can develop portal hypertension even before established cirrhosis) 2, 1
• Hereditary hemochromatosis 2
• Wilson's disease 2

Non-Cirrhotic (Presinusoidal/Mixed):

• Idiopathic non-cirrhotic portal hypertension (INCPH) - caused by thrombophilia (40% prevalence in Western patients), immunological disorders, specific medications (azathioprine, didanosine), and infections (HIV) 2, 3
• Schistosomiasis 2, 3
• Congenital hepatic fibrosis 2, 3
• Sarcoidosis 2, 3

Posthepatic Causes

Postsinusoidal:

• Sinusoidal obstruction syndrome (veno-occlusive disease) 2

Posthepatic:

• Budd-Chiari syndrome - thrombosis of hepatic veins or inferior vena cava 3
• Right heart failure 2

Pathophysiological Mechanisms

Portal hypertension develops through two primary mechanisms: 1, 4

• Increased intrahepatic vascular resistance - the dominant mechanism in cirrhosis, involving both structural changes (fibrosis, thrombosis, regenerative nodules) and functional vasoconstriction 4, 5
• Increased portal venous inflow - hyperdynamic splanchnic circulation that develops secondary to splanchnic vasodilation 6, 4

Critical Diagnostic Considerations

A common pitfall is misclassifying non-cirrhotic portal hypertension as cirrhosis radiologically, as patients with INCPH often demonstrate liver surface nodularity and portal vein wall thickening on ultrasound 2. Liver biopsy remains essential to exclude cirrhosis in suspected non-cirrhotic portal hypertension 2, 3.

The hepatic venous pressure gradient (HVPG) measurement pattern differs by etiology: In prehepatic and presinusoidal causes, HVPG remains normal because wedged pressure does not reflect portal pressure 2. This is crucial for interpreting hemodynamic studies correctly.