Background

Hepatic veno-occlusive disease (VOD) is a fatal liver condition caused due to blockages in small veins. 

Hepatic congestion from blockage causes fibrosis and liver failure. VOD is linked to high dose of chemotherapy in transplants. 

VOD is frequently seen in patients undergoing hematopoietic stem cell transplantation. Prolonged toxins exposure damages liver veins. 

It may appear acutely, sub-acutely, or chronically with abdominal pain, swelling, portal hypertension, enzyme elevations, and jaundice. 

It causes increase ALT and AST levels with mild alkaline phosphatase increases. 

Epidemiology

Patients undergoing myeloablative conditioning with busulfan/cyclophosphamide have higher risk of VOD, with incidence up to 20% to 60%. 

VOD can affect all ages but children with leukemia have higher risk. Children have higher VOD rates than adults due to different treatments and health conditions. 

High mortality rate observed in severe VOD up to 30% to 80% without treatment. Traditional remedies with pyrrolizidine alkaloids can increase risk of VOD due to toxin exposure. 

Anatomy

Pathophysiology

It is caused due to endothelial cell lesion in hepatic venules. Late histologic findings in liver disease include sinusoidal fibrosis, hepatocellular necrosis, and liver fibrosis. 

Endothelial cell injury leads to the release of pro-inflammatory cytokines and endothelial damage. 

Zone 3 is closest to central hepatic venules based on afferent arterial supply known as centrilobular. 

Etiology

Causes of VOD are: 

• Unrelated or HLA-mismatched donor 
• Non–T-cell-depleted transplant 
• Cirrhosis 
• Active viral hepatitis 
• Abdominal or hepatic irradiation 
• Metabolic syndrome 
• Thalassemia 
• Serum bilirubin 

Genetics

Prognostic Factors

Hepatic veno-occlusive disease linked to high mortality and morbidity. 

Mild cases usually resolve on their own, but severe cases related to liver failure and death. 

Multi-Organ Dysfunction Syndrome development in patients predicts poor prognosis with liver failure and organ dysfunction.  

Elevated bilirubin levels suggest severe liver dysfunction to increased mortality risk. 

Previous liver damage or toxic exposures worsen severity and prognosis outcome. 

Clinical History

The clinical history of hepatic veno-occlusive disease involves gathering information about precipitating factors, onset of symptoms and progression of symptoms of patients.  

Physical Examination

• Respiratory Examination 
• Abdominal Examination 
• Cardiovascular Examination 
• Neurological Examination 

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Mild symptoms are: 

Fatigue, malaise, and discomfort in mild right upper quadrant  

Severe symptoms are: 

jaundice, rapid weight gain and ascites 

Differential Diagnoses

• Budd-Chiari Syndrome 
• Acute Hepatic Graft-Versus-Host Disease 
• Right-Sided Heart Failure 
• Portal Vein Thrombosis 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Treatment for VOD focuses to restore normal blood flow and manage vasculitis and fibrin buildup in vessels. 

Defibrotide derived from porcine tissue has various therapeutic properties including antithrombotic, thrombolytic, anti-inflammatory, and anti-ischemic. 

Defibrotide is FDA approved drug for hepatic VOD treatment in adult and pediatric patients after stem cell transplantation. 

Anticoagulants are not recommended due to the risk of bleeding and lack of evidence in trails. 

Definitive treatment recommendations are not available thus various anticoagulant therapies are tried with mixed results. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

use-of-non-pharmacological-approach-for-hepatic-veno-occlusive-disease

Regular physical activity to improve overall well-being and reduce stress. 

Balance fluid intake and excretion to reduce the risk of fluid overload and renal complications. 

Proper awareness about hepatic VOD should be provided and its related causes with management strategies. 

Appointments with a physician and preventing recurrence of disorder is an ongoing life-long effort. 

Use of Antifibrinolytic/Antithrombotic Agent

Defibrotide: 

It increases the enzymatic activity of plasmin to hydrolyze fibrin clots. 

It is used to restore normal blood flow in hepatic sinusoids and reduce liver damage. 

use-of-intervention-with-a-procedure-in-treating-hepatic-veno-occlusive-disease

Paracentesis is used to relieve symptoms of ascites and to analyze ascitic fluid for signs of infection. 

Liver transplantation involves the surgical removal of the diseased liver and replacement with a healthy donor liver. 

use-of-phases-in-hepatic-veno-occlusive-disease

In the initial assessment phase, early detection initiates treatment promptly and prevents progression to severe disease. 

Pharmacologic therapy is effective in the treatment phase as it includes use of antifibrinolytic and antithrombotic agents.  

In supportive care and management phase, patients should receive required attention such as lifestyle modification and intervention therapies. 

The regular follow-up visits with the physician are scheduled to check the improvement of patients along with treatment response. 

Medication

Future Trends

Media Gallary

References

Sinusoidal Obstruction Syndrome (Veno-occlusive Disease) – LiverTox – NCBI Bookshelf (nih.gov)