Causes of Non-Cirrhotic Portal Hypertension
Non-cirrhotic portal hypertension results from vascular disorders in the portal system, granulomatous diseases, thrombophilic conditions, infections, medications, and genetic hepatobiliary disorders—all causing elevated portal pressure without cirrhotic architectural distortion. 1
Anatomical Classification Framework
The causes are best understood by anatomical location of the vascular resistance:
Prehepatic Causes
- Portal vein thrombosis is the most common prehepatic cause, often associated with underlying thrombophilia 1
- Splenic vein thrombosis creates isolated left-sided portal hypertension 1
Intrahepatic (Non-Cirrhotic) Causes
Vascular Disorders
- Idiopathic non-cirrhotic portal hypertension (INCPH) represents obliterative portal venopathy with three characteristic histological lesions: portal venopathy, nodular regenerative hyperplasia, and incomplete septal fibrosis 2
- Non-cirrhotic portal fibrosis (NCPF) is characterized by phlebosclerosis (obliterative portal venopathy), perisinusoidal fibrosis, and para-portal shunt vessels while maintaining lobular architecture 2
- Nodular regenerative hyperplasia can cause portal hypertension even in precirrhotic stages 1
Infectious Causes
- Schistosomiasis causes presinusoidal portal hypertension through granuloma formation with periportal fibrosis, particularly common in endemic regions 1, 3
- Chronic abdominal infections are the most important etiological factor in Eastern patients 4
Genetic/Metabolic Disorders
- Congenital hepatic fibrosis affects the hepatobiliary system through genetic alterations 1
- Sarcoidosis causes granulomatous infiltration leading to portal hypertension 1
Medication and Toxin Exposure
- Specific medications and toxic plant exposure can cause sinusoidal obstruction syndrome (veno-occlusive disease) 3
Posthepatic Causes
- Budd-Chiari syndrome results from thrombosis of hepatic veins or inferior vena cava 1
- Sinusoidal obstruction syndrome (veno-occlusive disease) obstructs hepatic venous outflow 1, 3
- Right heart failure causes backward transmission of elevated venous pressure 1
Etiological Categories for INCPH
When evaluating idiopathic non-cirrhotic portal hypertension specifically, screen for five categories:
- Thrombophilic disorders are identified in approximately 40% of Western patients and represent the most important factor in this population 2, 4
- Screen for inherited thrombophilias, myeloproliferative neoplasms, and antiphospholipid syndrome 2
- Immunological disorders including autoimmune conditions 4
- Chronic infections, particularly HIV 1, 4
- Medication or toxin exposure 4
- Genetic disorders affecting hepatobiliary function 4
Critical Diagnostic Pitfall
Patients with non-cirrhotic portal hypertension are frequently misclassified as cirrhotic on ultrasound due to liver surface nodularity and portal vein wall thickening. 2 A key distinguishing feature is transient elastography showing low liver stiffness (<12 kPa) despite signs of portal hypertension, which should prompt consideration of NCPH rather than cirrhosis 2. Liver biopsy that definitively excludes cirrhosis and advanced fibrosis remains essential for diagnosis 2, 1.
Hemodynamic Distinction
In prehepatic and presinusoidal causes, the hepatic venous pressure gradient (HVPG) remains normal because wedged pressure does not reflect portal pressure; therefore, measurement of intravariceal or intrasplenic pressure is needed to assess portal pressure accurately 1, 5.