Noncirrhotic Portal Hypertension

Noncirrhotic portal hypertension is raised portal venous pressure caused by prehepatic, intrahepatic or posthepatic disease that does not involve cirrhosis. It is classified by the site of resistance to flow.

It is a minority of portal hypertension in Western countries (about 3% to 5%) and a larger share in India and parts of Asia and in schistosomiasis endemic regions.

Causes by site:

• Prehepatic: portal or splenic vein thrombosis, arteriovenous fistula and massive splenomegaly.
• Presinusoidal intrahepatic: schistosomiasis, congenital hepatic fibrosis, sarcoidosis, primary biliary cholangitis (early), and porto sinusoidal vascular disease.
• Sinusoidal: nodular regenerative hyperplasia, amyloidosis and drug toxicity.
• Posthepatic: Budd-Chiari syndrome, sinusoidal obstruction syndrome, constrictive pericarditis and right heart failure.

Pathophysiology.

Resistance to flow at the level of the portal vein, the presinusoidal or sinusoidal compartment, or the hepatic outflow raises portal pressure. Hepatic venous pressure gradient is normal or mildly raised (under 10 mmHg) in presinusoidal disease. Splanchnic vasodilation adds to the portal pressure.

Variceal bleeding, splenomegaly with hypersplenism (low platelets, white cells), and portosystemic collaterals. Ascites and encephalopathy are less common and appear late. Liver function is preserved, and synthetic markers are near normal.

Red flags.

• Acute variceal bleeding.
• New ascites with abdominal pain (acute venous thrombosis).
• Hepatopulmonary syndrome or portopulmonary hypertension.

Exclude cirrhosis by combining elastography (liver stiffness often lower than cirrhotic ranges, with relatively high spleen stiffness), imaging and liver biopsy. Measure hepatic venous pressure gradient where available. Doppler ultrasound and cross-sectional imaging identify vascular disease. Endoscopy shows varices. Send liver tests, platelets, thrombophilia screen, viral and autoimmune serology, and schistosomiasis serology in endemic exposure.

Differential diagnosis.

• Cirrhosis.
• Budd-Chiari syndrome.
• Portal vein thrombosis.
• Hepatic schistosomiasis.
• Congenital hepatic fibrosis.
• Constrictive pericarditis.

Treat the cause and the portal hypertension.

• Propranolol: 20 to 40 mg orally twice daily, titrated to a resting heart rate of 55 to 60/min; long term; maximum 160 mg daily (80 mg with ascites); monitor heart rate, blood pressure and glucose; avoid in asthma and heart block.
• Carvedilol (alternative): 6.25 mg orally once daily for 3 days, then 12.5 mg once daily; long term; maximum 12.5 mg daily; monitor blood pressure (systolic 90 mmHg or more) and heart rate; reduce or stop with refractory ascites, low blood pressure or renal failure.
• Terlipressin (acute variceal bleeding): 2 mg IV every 4 hours for the first 24 to 48 hours, then 1 mg every 4 hours; up to 5 days; maximum 12 mg daily initially; monitor ischaemia, sodium and ECG; avoid in ischaemic heart disease and peripheral vascular disease.
• Ceftriaxone (acute bleeding): 1 g IV once daily; up to 7 days; maximum 2 g daily; monitor renal function and rash.

Add endoscopic variceal band ligation. Treat vascular thrombosis with anticoagulation (for example enoxaparin 1 mg/kg subcutaneously every 12 hours for 3 to 6 months; maximum 150 mg for each dose; monitor platelets and anti-Xa in renal impairment; use 1 mg/kg once daily when creatinine clearance is under 30 mL/min).

Use praziquantel 40 mg/kg orally in 2 doses on one day (maximum 3 g in a single day; monitor for dizziness; reduce in severe hepatic impairment) for schistosomiasis. Transjugular intrahepatic portosystemic shunt or surgical shunt is used for refractory bleeding. Liver transplantation is rarely needed unless liver failure arises.

Monitoring. Endoscopy for variceal surveillance every 1 to 2 years once eradicated, blood counts, liver tests and Doppler yearly.

Referral and escalation. Hepatology, interventional radiology and surgery for shunts.