Hepatic venous outflow obstruction: Three similar syndromes

Table 1 Definition, etiology and histology of VOD, BCS, and CH

	VOD	BCS	CH
Site of venous obstruction	Hepatic sinusoids and terminal venules	From hepatic veins to the superior end of IVC	Heart
Etiology	Sinusoidal endothelial injury due to HSCT, chemotherapy, abdominal radiotherapy, and pyrrolizidine alkaloids	Hepatic vein thrombosis, IVC webs, compression of hepatic veins or IVC by tumor, cyst, or abscess	Increased right atrial pressure due to CHF (CAD, cardiomyopathies, valve abnormalities), cor pulmonale (COPD, ILD, pulmonary HTN), and pericardial disease (constrictive pericarditis, pericardial tamponade)
Histology	Changes predominantly in perivenular areas	Predominantly in perivenular areas except in presence of concomitant PVT.	Predominantly in perivenular areas Sinusoidal congestion and hepatocellular necrosis
	Gaps in SEC barrier leading to subendothelial edema	Sinusoidal congestion followed by ischemic cell necrosis and bridging fibrosis between central veins	Bridging fibrosis between central veins leading to cardiac fibrosis in chronic cases
	Narrowing of central veins and sinusoids with sinusoidal congestion and hepatocellular necrosis	Caudate lobe hypertrophy, with fibrosis and atrophy in the rest of liver
	Collagen accumulation in sinusoids and veins leading to bridging fibrosis between central veins

VOD: Veno-occlusive disease, BCS: Budd-Chiari Syndrome, CH: Congestive hepatopathy, IVC: Inferior vena cava, HSCT: Hematopoietic stem cell transplantation, CHF: Congestive heart failure, CAD: Coronary artery disease, COPD: Chronic obstructive pulmonary disease, ILD: Interstitial lung disease, SEC: Sinusoidal endothelial cell, PVT: Portal vein thrombosis.

Table 2 Radiological findings, treatment, and prognosis in VOD, BCS, and CH

	VOD	BCS	CH
Radiological findings	Ultrasonography to rule out other liver disorders	Doppler: Abnormal flow in a hepatic vein; large intrahepatic collateral vessels; e nlarged, stenotic, or tortuous hepatic veins	Dilatation of all three hepatic veins on sonogram
	Doppler may show reverse blood flow in the portal vein	MRI: Large intrahepatic comma shaped c ollaterals. Hepatic venography: Spider web venous network pattern	ECHO: Increased pulmonary artery pressure, dilatation of right side of heart, TR, abnormal diastolic ventricular filling due to pericardial disease
Treatment	(1) Prevention: UDCA, heparin, LMWH, and defibrotide	(1) Prevention of thrombus extension: Anticoagulation with heparin and warfarin	Treatment of the underlying heart disease
	(2) Treatment: Symptomatic care, defibrotide, tPA, AT-III concentrate	(2) Restoration of blood flow: Thrombolytic therapy, percutaneous, angioplasty, TIPS, or shunt surgery	Pericardiectomy in constrictive pericarditis
	(3)TIPS and liver transplantation in selected cases	(3) Liver transplantation
Prognosis	Mortality rate between 9% to 98% depending on the severity	Five-year survival rate 42% to 89% in hepatic vein thrombosis and 25% in IVC obstruction	Liver disease rarely contributes to mortality in these patients

MRI: Magnetic resonance imaging, TR: Tricuspid regurgitation, ECHO: Transthoracic echocardiogram UDCA: Ursodeoxycholic acid, LMWH: Low-molecular weight heparin, tPA: Tissue plasminogen activator, AT-III: Anti-thrombin III, TIPS: Transjugular intrahepatic portosystemic shunt.

Table 3 Diagnostic criteria for veno-occlusive disease

Seattle criteria

Development of at least 2 of the following 3 clinical features before d 30 after transplantation

Jaundice

Hepatomegaly with right upper quadrant pain

Ascites and/or unexplained weight gain

Baltimore criteria

Development of hyperbilirubinemia with serum bilirubin > 2 mg/dL within 21 d after transplantation and at least 2 of the following clinical signs and symptoms

Hepatomegaly, which may be painful

Weight gain > 5% from baseline

Ascites

Table 4 Differential diagnosis of veno-occlusive disease

Cholangitis lenta (sepsis-related cholangitis)

Drug/parenteral nutrition induced hepatotoxicity/cholestasis

Acute graft-versus-host disease

Fungal infection

Viral hepatitis

Congestive heart failure

Table 5 Causes of the Budd-Chiari Syndrome

Common causes

Hypercoagulable states

Inherited thrombophilic disorders

Antithrombin III deficiency

Protein C deficiency

Protein S deficiency

Factor V Leiden mutation

Prothrombin gene mutation

Acquired procoagulative disorders

Myeloproliferative disorders (overt and occult)

Paroxysmal nocturnal hemoglobinuria

Antiphospholipid syndrome

Cancer

Pregnancy

Use of oral contraceptives

Uncommon causes

Tumoral invasion

Hepatocellular carcinoma

Renal cell carcinoma

Adrenal carcinoma

Miscellaneous

Aspergillosis

Behcet’s syndrome

Inferior vena caval webs

Trauma

Inflammatory bowel syndrome

Dacarbazine therapy

Idiopathic