What are the diagnostic criteria and treatment options for Veno-Occlusive Disease (VOD) of the liver?

Diagnostic Criteria for Hepatic Veno-Occlusive Disease (VOD/SOS)

Diagnose VOD/SOS primarily using the Seattle or Baltimore clinical criteria after excluding other causes, recognizing that up to 20% of cases cannot be diagnosed with certainty using clinical features alone. 1

Clinical Diagnostic Criteria

The diagnosis relies on a high index of clinical suspicion in the appropriate context (post-HSCT, chemotherapy, or immunosuppression) combined with established clinical criteria: 1

Modified Seattle/Baltimore Criteria

• Serum bilirubin ≥2 mg/dL (sensitive but not specific marker) 1
• Plus at least two of the following by Day +21 post-HSCT: 2
  • Hepatomegaly (often painful)
  • Ascites
  • Weight gain >5%

Severe VOD Definition

Severe VOD is defined as VOD occurring with multi-organ dysfunction (renal or pulmonary) by Day +28 post-HSCT. 2 Specifically:

• Renal dysfunction requiring dialysis, OR
• Any noninfectious pulmonary abnormality 3

Laboratory and Imaging Findings

Serum Markers

• Elevated bilirubin is the most sensitive marker but lacks specificity 1
• Other proposed markers (not yet independently validated): 1
  • Serum procollagen
  • Plasminogen activator inhibitor-1 (PAI-1) - not recommended for routine diagnostic work-up 4
  • Platelet count <167,000/μL
  • Elevated APRI or FIB-4 scores

Imaging Studies

• Doppler ultrasound is the first-line imaging modality to exclude other disorders 1, 4
  • May show portal hypertension signs, hepatosplenomegaly
  • Reversal of portal vein flow and monophasic hepatic vein flow suggest VOD but lack sensitivity 1
• CT scan is not recommended due to contrast agent toxicity 1
• MRI may show patchy signal enhancement compatible with severe SOS 1

Definitive Diagnosis

Transjugular liver biopsy combined with hepatic venous pressure gradient (HVPG) measurement provides the most definitive diagnosis. 1

Histopathologic Features

• Loss of sinusoidal wall integrity with endothelial cell injury and detachment 1
• Centrilobular hepatocellular necrosis (variable degrees) 1
• Centrilobular perisinusoidal and endovenular fibrosis 1
• Occlusion of centrilobular veins occurs in only 50% of mild-moderate cases and 75% of severe cases 1
• Associated findings: peliosis, nodular regenerative hyperplasia (NRH) - requires reticulin staining 1

Hemodynamic Criteria

HVPG >10 mmHg has 52% sensitivity and 91% specificity with >85% positive predictive value for VOD diagnosis in HSCT context. 1

When to Perform Liver Biopsy

• Reserve for cases where diagnosis is unclear and other diagnoses must be excluded 4
• Use transjugular approach to reduce bleeding risk, as percutaneous biopsy is often contraindicated by thrombocytopenia, coagulopathy, or ascites 1, 4
• Biopsy findings influence treatment decisions in approximately 90% of patients 1

Critical Diagnostic Pitfalls

• Timing varies by regimen - clinical onset delay after therapy initiation differs, and some features may be absent 1
• Patchy distribution of lesions means sampling error can occur 1
• Sensitivity and specificity of Seattle/Baltimore criteria are not well-defined across different VOD etiologies 1
• Must exclude other mimicking causes before confirming diagnosis (see differential diagnosis considerations) 1

Context-Specific Considerations

Consider VOD/SOS diagnosis whenever liver disease occurs in patients with: 1

• Haematopoietic stem cell transplantation
• Chemotherapy for cancers (especially oxaliplatin, busulfan, cyclophosphamide) 1
• Immunosuppression for solid organ transplantation or inflammatory bowel disease 1
• Exposure to pyrrolizidine alkaloids or other hepatotoxins 1