Portal Vein Hypertension: Causes and Classification
Portal hypertension is classified anatomically into three categories based on the site of increased resistance to blood flow: prehepatic, intrahepatic, and posthepatic, with cirrhosis from chronic liver disease being the single most common cause overall. 1
Anatomical Classification System
Portal hypertension develops when blood flow is impeded at any level within the portal system, requiring classification by anatomic location 2:
Prehepatic Causes
- Portal vein thrombosis is the most common prehepatic cause 1
- Splenic vein thrombosis 1
- Mesenteric vein obstruction 2
Intrahepatic Causes (Most Common Category)
Cirrhotic causes:
- Cirrhosis from any chronic liver disease accounts for the majority of portal hypertension cases in Western countries 2, 3, 1
- Chronic viral hepatitis B and C 1
- Alcoholic liver disease 1
- Non-alcoholic steatohepatitis (NASH) 1
- Autoimmune hepatitis 1
- Primary biliary cirrhosis (can develop portal hypertension even before established cirrhosis) 1
- Hereditary hemochromatosis 1
- Wilson's disease 1
Non-cirrhotic intrahepatic causes:
- Idiopathic non-cirrhotic portal hypertension (INCPH), caused by thrombophilia (40% prevalence), immunological disorders, specific medications, or HIV infection 1
- Schistosomiasis 1
- Congenital hepatic fibrosis 1
- Sarcoidosis 1
- Nodular regenerative hyperplasia 1
Posthepatic Causes
- Budd-Chiari syndrome (thrombosis of hepatic veins or inferior vena cava) 1
- Sinusoidal obstruction syndrome (veno-occlusive disease) 1
- Right heart failure 1
Pathophysiological Mechanisms
Portal hypertension develops through two primary mechanisms 1:
- Increased intrahepatic vascular resistance - the primary factor, determined by morphological changes in chronic liver disease and aggravated by active contraction of porto-hepatic bed elements 4
- Increased portal venous inflow - caused by splanchnic arteriolar vasodilation and hyperkinetic circulation 4
The dynamic component of increased resistance is reversible and involves decreased nitric oxide synthesis in the intrahepatic circulation 4.
Diagnostic Considerations by Etiology
A critical diagnostic pitfall: In prehepatic and presinusoidal causes, hepatic venous pressure gradient (HVPG) remains normal because wedged pressure does not reflect portal pressure 1. This means HVPG measurement pattern differs by etiology and cannot be relied upon for all causes.
Evaluating Non-Cirrhotic Portal Hypertension
When portal hypertension presents without known liver disease 1:
- Start with Doppler ultrasound to assess portal and hepatic vein patency
- Liver biopsy is essential to exclude cirrhosis and identify specific pathology like nodular regenerative hyperplasia or obliterative portal venopathy
- Thrombophilia workup is necessary if INCPH is suspected, as 40% have underlying prothrombotic conditions
Clinical presentation differences: 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.
Hemodynamic Definitions
Understanding pressure thresholds is critical for management decisions 3, 5:
- Normal HVPG: 1-5 mmHg
- Portal hypertension: >5 mmHg (HVPG ≥6 mmHg)
- Clinically significant portal hypertension (CSPH): ≥10 mmHg (when complications like varices and ascites develop)
- High mortality risk: ≥16 mmHg (independently associated with higher mortality in both compensated and decompensated cirrhosis) 2
Common Pitfalls to Avoid
- Do not assume all portal hypertension is cirrhotic - systematically exclude prehepatic and posthepatic causes, especially in patients with preserved liver function 1
- Do not rely solely on HVPG in suspected prehepatic or presinusoidal disease, as it will be falsely normal 1
- Do not overlook thrombophilia workup in non-cirrhotic portal hypertension, as 40% have prothrombotic conditions requiring specific management 1
- Recognize that primary biliary cirrhosis can cause portal hypertension before cirrhosis is established, requiring earlier surveillance 1