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19th

International Liver Support Meeting Rostock

Cytosorb® Hemoadsorprtion for Removal of Bilirubin and Bile Acids in a Case of Persistent Severe Intrahepatic Cholestasis due to Graft-versus-host Disease and Drug Toxicity

Introduction:
Cholestatic liver failure without treatable cause carries a grave prognosis. Intracellular accumulation of hydrophobic unconjugated bile acids causes oxidative stress, mitochondrial toxicity, and finally hepatocyte apoptosis [Dig Liver Dis 2002, 34: 387]. Evidence is mounting that hyperbilirubinemia may induce oxidative stress and apoptosis, too [J Hepatol 2002, 36:335; Clin Chim Acta 2006, 374: 46]. Moreover, cholestasis adversely affects the whole body by evoking systemic inflammation and impeding unspecific immune defense [Curr Opin Crit Care 2013, 19:128]. The absence of bile acids in the ileum promotes bacterial overgrowth and translocation.

Considering its principal action, hemoadsorption with Cytosorb would be expected to remove albumine-bound substances up to a molecular size of 60 kDa, including bilirubin and hydrophobic bile acids. In patients with septic shock and septic cholestasis, Cytosorb hemoadsorption for cytokine removal was found to reduce bilirubin, too.

We report the case of a 38 years old male with intrahepatic cholestasis due to graft-versus-host disease and drug toxicity who was successfully treated with Cytosorb hemoadsorption to lower blood levels of bilirubin and bile acids to facilitate recovery of liver function.

Case:
Past medical history:

  • B-cell chronic lymphocytic leukemia (B-CLL), CD38+, initial stage Binet C, with cytogenetic abnormalities indicating a high risk disease, first diagnosed August 2013
  • allogeneic stem cell transplantation July 2014
  • severe graft-versus-host disease (GVHD):
  • skin grade III, liver grade I, lung grade III
  • treated with mycophenolate, methylprednisolone, cyclosporine, and extracorporeal photophoresis (ongoing)

Present illness and therapy:

  • admission to the intensive care unit (ICU) for respiratory failure due to aspergillus pneumonia with septic shock antimycotic therapy with liposomal amphothericin B, long-term intensive care including ventilation, tracheostomy and continuous renal replacement therapy
  • previous liver GVHD and initially mild elevation of liver parameters (bilirubin 27.7 µmol/l, GPT 2.5 µkatl/l, GOT 1.8 µkatal/l, GGT 10 µkatal/l) no triazole antifungal therapy for fear of hepatotoxicity
  • immunosuppressive therapy with ruxolitinibe, methylprednisolone, mycophenolate, ciclosporin
  • remission of pneumonia, prolonged weaning from mechanical ventilation, but
  • development of severe intrahepatic cholestasis, bilirubin up to 420 µmol/l (conjugated: 295 µmol/l)
  • biliary tract obstruction and hepatobiliary malperfusion ruled out,
  • cessation of mycophenolate therapy and dose increase of methylprednisolone without effect on cholestasis,
  • no other drugs typically causing drug-induced cholostasis,
  • transjugular liver biopsy: mild chronic inflammation of periportal fields and acini, mild cholestasis, suspected low-grade GVHD or drug toxicity
  • no spontaneous improvement: bilirubin > 350 µmol/l for 24 days
  • treatment attempt with Cytosorb® hemoadsorption, standalone configuration, citrate anticoagulation, blood flow 250 ml/min, 7 cycles over 15 days.
  • Result: effective lowering of bilirubin and bile acid levels to subcritical values, spontaneous further decrease to normal values over 6 months

Conclusion:
In persistent severe intrahepatic cholestasis, Cytosorb® hemoadsorption may be a therapeutic option facilitating long-term recovery of liver function.

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