The following data refer to a 34-year-old male admitted to ICU twenty days after an allogeneic stem cell transplant for acute myeloid leukaemia. Over the last few days he has been complaining of right upper quadrant abdominal pain, and observed to have gained several kilograms in weight.

Venous Biochemistry

Parameter

Patient Value

Adult Normal Range

Sodium

142 mmol/L

135 – 145

Potassium

4.8 mmol/L*

3.5 – 4.5

Chloride

97 mmol/L

95 – 105

Bicarbonate

22 mmol/L

22 – 26

Urea

11.2 mmol/L*

2.9 – 8.2

Creatinine

134 μmol/L*

70 – 120

Calcium

2.13 mmol/L

2.10 – 2.55

Phosphate

1.21 mmol/L

0.65 – 1.45

Total bilirubin

342 μmol/L*

0 – 25

Aspartate aminotransferase (AST)

175 U/L*

< 40

Gamma glutamyl transferase (GGT)

123 U/L*

< 40

Alanine aminotransferase (ALT)

87 U/L*

< 40

  1. Give the most likely diagnosis. (10% marks)
  1. What are the characteristic findings on liver ultrasound scan? (10% marks)

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College answer

a) Veno-occlusive disease of the liver (sinusoidal obstruction syndrome)

b) ascites and reversal of portal vein flow. (2 marks)

Discussion

The stem gives us everything needed to make the diagnosis here. The biochemical abnormalities are:

  • A kidney injury
  • Massively raised bilirubin
  • Relatively trivial elevation of liver enzymes

The combination of these findings with a recent history of BMT suggests strongly that veno-occlusive disease has developed. Both the Seattle and Baltimore criteria need a recent BMT, raised bilirubin and weight gain:

Seattle criteria:

  • Two or more of the following:
    • Bilirubin > 34mmol/L
    • Hepatomegaly
    • RUQ pain
    • Weight gain >2%
  • Within 20 days of BMT

Baltimore criteria:

  • Bilirubin > 34mmol/L,
    AND two or more of the following:
    • Hepatomegaly
    • Ascites
    • Weight gain >5%
  • Within 21 days of BMT

Diagnosis does not require ultrasound, but it is usually ordered in this context. The BCSH/BSBMT guidelines (2013) concluded that "the main role of ultrasound is to exclude the presence of other diagnoses" because the ultrasound findings which are usually associated with VOD are insufficiently sensitive and specific. In any case, here they are:

  • Ultrasound-confirmed ascites
  • Ultrasound-confirmed hepatomegaly
  • Splenomegaly
  • Attenuated or reversed hepatic venous flow
  • Thickened gallbladder wall
  • Ultrasound evidence of increasing hepatic artery  vascular resistance (there is a "hepatic artery vascular resistance index",  which is helpful in the diagnosis if it is greater than 0.75.)

References

References

Baron, Frédéric, Manuel Deprez, and Yves Beguin. "The veno-occlusive disease of the liver." Haematologica 82.6 (1997): 718-725.

Dignan, Fiona L., et al. "BCSH/BSBMT guideline: diagnosis and management of veno‐occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation." British journal of haematology 163.4 (2013): 444-457.

Richardson, Paul G., et al. "Defibrotide for the treatment of severe hepatic veno-occlusive disease and multiorgan failure after stem cell transplantation: a multicenter, randomized, dose-finding trial." Biology of Blood and Marrow Transplantation 16.7 (2010): 1005-1017.

Couriel, Daniel, et al. "Acute graft‐versus‐host disease: Pathophysiology, clinical manifestations, and management." Cancer 101.9 (2004): 1936-1946.

Ljungman, Per, Paul Griffiths, and Carlos Paya. "Definitions of cytomegalovirus infection and disease in transplant recipients." Clinical Infectious Diseases 34.8 (2002): 1094-1097.

Bearman, Scott I. "The syndrome of hepatic veno-occlusive disease after marrow transplantation." Blood 85.11 (1995): 3005-3020.

Coppell, Jason A., et al. "Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome." Biology of Blood and Marrow Transplantation 16.2 (2010): 157-168.

Mcdonald, George B., et al. "Venocclusive disease of the liver after bone marrow transplantation: diagnosis, incidence, and predisposing factors."Hepatology 4.1 (1984): 116-122.

Jones, Richard J., et al. "Venoocclusive disease of the liver following bone marrow transplantation." Transplantation 44.6 (1987): 778-783.

Kumar, Ashish, Praveen Sharma, and Shiv Kumar Sarin. "Hepatic venous pressure gradient measurement: time to learn." Indian J Gastroenterol 27.2 (2008): 74-80.

Cheuk, D. K., et al. "Interventions for prophylaxis of hepatic veno-occlusive disease in people undergoing haematopoietic stem cell transplantation." The Cochrane database of systematic reviews 5 (2015): CD009311-CD009311.

Mohty, M., et al. "Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation." Bone marrow transplantation 51.7 (2016): 906-912.