Canterbury DHB

Context

Veno Occlusive Disease of the Liver (VOD)

In This Section

Pathogenesis

Clinical Features and Diagnosis

Grading of VOD

Prognosis

Management of VOD

Pathogenesis

Veno-occlusive disease, also known as sinusoidal obstructive syndrome (SOS) is a life-threatening complication of HCT. It occurs typically before day 30 and is more common after allogeneic than autologous transplantation. It is thought to occur due to conditioning regimen-induced injury to the vascular endothelial cells in zone 3 of the liver resulting in activation of pro-inflammatory pathways, e.g. TNF. Extravasation of cells between the damaged endothelial cells leads to extraluminal compression of the sinusoids resulting in obstruction. Injury to the endothelial cells also triggers a pro-coagulant effect leading to further narrowing of the sinusoids. Hepatic venous outflow obstruction leads to portal venous flow reversal and hepato-renal syndrome.

Clinical Features and Diagnosis

A clinical syndrome of raised bilirubin, enlarged liver, ascites and fluid retention post SCT with an onset usually by day +30.

The differential diagnosis includes hyperacute GvHD, cholestasis of sepsis, medication, biliary obstruction and fungal abscess.

USS may be useful and is non-invasive but should not delay treatment. Findings that suggest VOD are ascites, reversal of portal flow, hepatic artery resistance index 0.75 and abnormal portal vein waveform.

Liver biopsy is technically difficult and has a high rate of complications in this patient population but if required should be performed by an interventional radiologist using the trans-jugular approach. It is not performed routinely.

Clinical Features and Diagnosis of VOD

Grading of VOD

 

Mild

Moderate

Severe

Bilirubin (mmol/L)

<85.5

85.5-136.8

>136.8

Liver function

<3x ULN

3-8x ULN

>8x ULN

Weight gain

<2%

2-5%

>5%

Renal function

Normal

<2x ULN

>2x ULN

Rate of change

Slow

Moderate

Rapid

From Chao, N. (2014). "How I treat sinusoidal obstruction syndrome." Blood 123(26): 4023-4026.

Prognosis

Mild to moderate VOD usually resolves completely with supportive treatment including symptom control and diuretics.

The day +100 mortality in severe VOD with multi-organ failure is approximately 80% with a strong correlation with response to treatment. Non-responders have a day +100 mortality of approximately 90%.

Management of VOD

Prophylaxis

Very high risk patients for VOD include:

Monitoring

Treatment

All patients

  • Early consult with ICU and hepatologist
  • Analgesia
  • Daily monitoring as above

Based on severity

  • Dialysis
  • Drainage of ascites
  • Defibrotide 25 mg/kg/day IV in 4 divided doses
  • Early treatment is associated with improved outcomes

Other treatments

Thrombolytic therapy, prostacycline, prednisone, anti thrombin III and activated protein C are all ineffective and/or carry unacceptable side effects. Porto-systemic shunts also carry high risks. Liver transplantation has been used successfully in patients severely affected by VOD but who have an otherwise good prognosis.

Further reading

About this Canterbury DHB document (9084):

Document Owner:

Andrew Butler (see Who's Who)

Issue Date:

December 2016

Next Review:

December 2018

Keywords:

Note: Only the electronic version is controlled. Once printed, this is no longer a controlled document. Disclaimer

Topic Code: 9084