What are the causes of high portal vein pressure (portal hypertension)?

Causes of High Portal Vein Pressure

Portal hypertension develops from two primary mechanisms: increased resistance to portal blood flow (predominantly intrahepatic) and increased portal venous inflow from splanchnic vasodilation, with cirrhosis from chronic liver disease being the overwhelming cause in clinical practice. 1, 2

Anatomical Classification of Causes

Portal hypertension is classified by the anatomical site of increased resistance into three categories: prehepatic, intrahepatic, and posthepatic. 2

Prehepatic Causes

• Portal vein thrombosis is the most common prehepatic cause, occurring when the obstruction is located before blood enters the liver. 2
• Splenic vein thrombosis can cause isolated left-sided (sinistral) portal hypertension. 2
• Mesenteric vein obstruction represents another prehepatic etiology. 2

Intrahepatic Causes (Most Common Overall)

Cirrhosis from any chronic liver disease accounts for the vast majority of portal hypertension cases and is the single most important cause. 1, 2

Cirrhotic Causes:

• Chronic viral hepatitis B and C are major causes of cirrhosis leading to portal hypertension. 2, 3
• Alcoholic liver disease is a leading cause, particularly in Western countries. 2
• Non-alcoholic steatohepatitis (NASH) is an increasingly common cause. 2, 3
• Autoimmune hepatitis can progress to cirrhosis with portal hypertension. 2
• Primary biliary cirrhosis is notable because it can develop portal hypertension even before established cirrhosis develops. 4, 2
• Hereditary hemochromatosis causes iron overload leading to cirrhosis. 2
• Wilson's disease causes copper accumulation and cirrhotic changes. 2

Non-Cirrhotic Intrahepatic Causes:

• Idiopathic non-cirrhotic portal hypertension (INCPH) is caused by thrombophilia (40% of cases), immunological disorders, specific medications, and infections including HIV. 2, 3
• Schistosomiasis causes periportal fibrosis without cirrhosis. 2
• Congenital hepatic fibrosis is a developmental disorder causing portal hypertension. 2
• Sarcoidosis can cause granulomatous infiltration leading to portal hypertension. 2
• Nodular regenerative hyperplasia can cause portal hypertension even in precirrhotic stages. 2

Posthepatic Causes

• Budd-Chiari syndrome results from thrombosis of hepatic veins or inferior vena cava. 2
• Sinusoidal obstruction syndrome (veno-occlusive disease) causes obstruction at the hepatic venule level. 2
• Right heart failure causes hepatic congestion and elevated portal pressures. 2

Pathophysiological Mechanisms

Portal pressure increases through a dual mechanism that perpetuates itself:

Increased Intrahepatic Resistance (Primary Driver)

• Structural component (70%): Architectural distortion from fibrous tissue, regenerative nodules, vascular distortion, and microthrombi. 4, 3
• Functional component (30%): Active intrahepatic vasoconstriction due to decreased nitric oxide production and endothelial dysfunction. 4, 3, 5
• Activated hepatic stellate cells alter sinusoidal blood flow after activation, contributing significantly to increased resistance. 3

Increased Portal Blood Inflow (Aggravating Factor)

• Splanchnic arteriolar vasodilation occurs concomitantly with collateral formation, paradoxically increasing portal blood flow despite the development of portosystemic collaterals. 4, 5, 6
• Hyperkinetic circulation develops as the disease progresses, further elevating portal pressure. 5

Critical Diagnostic Considerations

Hemodynamic Thresholds

• Normal HVPG: 1-5 mmHg 1, 3
• Portal hypertension: HVPG >5 mmHg 3
• Clinically significant portal hypertension (CSPH): HVPG ≥10 mmHg (when varices and complications develop) 1, 2, 3
• High mortality risk: HVPG ≥16 mmHg 1, 3

Important Diagnostic Pitfalls

• HVPG patterns differ by etiology: In prehepatic and presinusoidal causes, HVPG remains normal because wedged pressure does not reflect portal pressure. 2
• INCPH is often misclassified: Patients are radiologically misdiagnosed as cirrhotic, but a clue is low liver stiffness (<12 kPa) despite signs of portal hypertension. 3
• Liver biopsy remains essential to exclude cirrhosis in suspected non-cirrhotic portal hypertension. 2, 3
• Screening for thrombophilia is necessary if INCPH is suspected, as 40% have underlying prothrombotic conditions. 2, 3

Special Population Considerations

• Patients with hepatitis C and bridging fibrosis can develop varices even without established cirrhosis (16% prevalence). 4
• Myeloproliferative disease and antiphospholipid syndrome patients should be screened for extrahepatic portal vein obstruction. 3