Porto-Sinusoidal Vascular Disease

Porto sinusoidal vascular disease (PSVD) is a group of liver vascular disorders with or without portal hypertension, in which hepatic histology shows specific lesions of the portal venules and sinusoids and cirrhosis is absent. The term replaces idiopathic non-cirrhotic portal hypertension, hepatoportal sclerosis, nodular regenerative hyperplasia and incomplete septal cirrhosis.

Cirrhosis is excluded, and the diagnosis needs either specific histological lesions or specific clinical signs of portal hypertension (varices, portosystemic collaterals, splenomegaly over 13 cm, ascites after exclusion of other causes, or a hepatic venous pressure gradient under 10 mmHg despite portal hypertension).

Uncommon, affecting adults of 30 to 50 years of age, with male predominance in Western series.

Associations are HIV infection and antiretrovirals (didanosine), immune disorders (common variable immunodeficiency, autoimmune and connective tissue disease), prothrombotic states and portal vein thrombosis (up to 30%), drugs (azathioprine, thioguanine, oxaliplatin), toxins (arsenic, vinyl chloride), haematological disease and genetic syndromes (telomere disease, Adams-Oliver syndrome).

Pathophysiology.

Injury to the portal venules and sinusoids causes obliterative portal venopathy, nodular regeneration and perisinusoidal fibrosis. This raises presinusoidal resistance, producing portal hypertension with a normal or mildly raised hepatic venous pressure gradient.

Often asymptomatic, detected by abnormal liver tests or splenomegaly. Variceal bleeding, hypersplenism, ascites, hepatic encephalopathy, hepatopulmonary syndrome, portopulmonary hypertension and portal vein thrombosis occur. Synthetic function is usually preserved.

Red flags.

• Acute variceal bleeding.
• Portal vein thrombosis with abdominal pain.
• Dyspnoea with hypoxaemia.

Liver biopsy (adequate length, at least 2 cm and 10 portal tracts if possible) with reticulin and Masson stains is the key test and shows obliterative portal venopathy, nodular regenerative hyperplasia, periportal fibrosis or incomplete septal fibrosis without cirrhosis. Elastography shows liver stiffness lower than in cirrhosis, with a high spleen stiffness. Hepatic venous pressure gradient is normal or mildly raised.

Doppler and cross-sectional imaging assess vessels and spleen. Test for thrombophilia, HIV, autoimmune and immunodeficiency disease, and review drugs and toxins. Endoscopy screens for varices.

Differential diagnosis.

• Cirrhosis.
• Extrahepatic portal vein obstruction.
• Budd-Chiari syndrome.
• Schistosomiasis.
• Congenital hepatic fibrosis.
• Sinusoidal obstruction syndrome.
• Primary biliary cholangitis (early).

Stop causative drugs and toxins, treat the associated disease, and manage portal hypertension.

• Carvedilol: 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, renal failure or sepsis.
• Propranolol (alternative): 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.
• 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 band ligation for varices, and anticoagulation for portal vein thrombosis.

Enoxaparin 1 mg/kg subcutaneously every 12 hours for 3 to 6 months or longer in persistent prothrombotic disease; maximum 150 mg for each dose; monitor platelets, bleeding and anti-Xa in renal impairment; use 1 mg/kg once daily when creatinine clearance is under 30 mL/min.

Transjugular intrahepatic portosystemic shunt is used for refractory bleeding or ascites. Liver transplantation is considered for liver failure or complications such as portopulmonary hypertension.

Monitoring. Endoscopic surveillance, blood counts, liver tests and Doppler imaging; repeat elastography yearly.

Referral and escalation. Hepatology with expertise in vascular liver disease, haematology, immunology and, when needed, transplant centre referral.