What causes portal hypertension?

What Causes Portal Hypertension

Cirrhosis from any chronic liver disease is the single most common cause of portal hypertension overall, accounting for the majority of cases in Western countries. 1

Anatomical Classification of Causes

Portal hypertension is classified by the site of increased resistance to blood flow into three main categories: prehepatic, intrahepatic, and posthepatic. 1

Prehepatic Causes

• Portal vein thrombosis is the most common prehepatic cause of portal hypertension 1
• Splenic vein thrombosis represents another prehepatic etiology 1
• Mesenteric vein obstruction also causes prehepatic portal hypertension 1

Intrahepatic Causes (Most Common Category)

Cirrhotic causes:

• Chronic viral hepatitis B and C lead to cirrhosis and subsequent portal hypertension 1
• Alcoholic liver disease is a major intrahepatic cause 1
• Non-alcoholic steatohepatitis (NASH) increasingly contributes to portal hypertension 1
• Autoimmune hepatitis causes intrahepatic portal hypertension 1
• Primary biliary cirrhosis can develop portal hypertension even before established cirrhosis 1
• Hereditary hemochromatosis and Wilson's disease are genetic causes 1

Non-cirrhotic intrahepatic causes:

• Idiopathic non-cirrhotic portal hypertension (INCPH) results from thrombophilia, immunological disorders, specific medications, and infections 1
• Schistosomiasis is a parasitic cause, particularly important in endemic regions 1
• Congenital hepatic fibrosis causes non-cirrhotic portal hypertension 1
• Sarcoidosis can lead to portal hypertension without cirrhosis 1
• Nodular regenerative hyperplasia causes portal hypertension even in precirrhotic stages 1

Posthepatic Causes

• Budd-Chiari syndrome, characterized by thrombosis of hepatic veins or inferior vena cava, is a major posthepatic cause 1
• Sinusoidal obstruction syndrome (veno-occlusive disease) represents another posthepatic etiology 1
• Right heart failure causes posthepatic portal hypertension through increased venous back-pressure 1

Pathophysiological Mechanisms

Portal hypertension develops through two primary mechanisms: 1

1. Increased intrahepatic vascular resistance - This is the dominant mechanism in cirrhosis, resulting from structural changes (fibrosis, nodular regeneration) and functional changes (dysregulation of liver sinusoidal endothelial cells and hepatic stellate cells) 2

2. Increased portal venous inflow - Hyperdynamic circulation develops with splanchnic vasodilation, increasing blood flow to the portal system and aggravating portal hypertension 2

Critical Diagnostic Considerations

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. 1 This is a critical pitfall when interpreting HVPG results.

Liver biopsy remains essential to exclude cirrhosis in suspected non-cirrhotic portal hypertension. 1 When evaluating portal hypertension without known liver disease, systematic exclusion of all causes is necessary, starting with Doppler ultrasound to assess portal and hepatic vein patency. 1

In patients with non-cirrhotic portal hypertension, a thrombophilia workup is necessary if INCPH is suspected, as 40% of patients have underlying prothrombotic conditions. 1

Clinical Context

Portal hypertension is defined as HVPG >5 mmHg, with clinically significant portal hypertension (CSPH) occurring at HVPG ≥10 mmHg, when complications like varices and ascites develop. 1 HVPG ≥16 mmHg is independently associated with higher mortality in both compensated and decompensated cirrhosis. 1

Patients with non-cirrhotic portal hypertension typically present with splenomegaly and hypersplenism, variceal bleeding, normal or near-normal liver function at diagnosis, and a better prognosis than cirrhotic portal hypertension. 1