Supplementary Table 1 Individual patient characteristics
Patient 1 Patient 2 Patient 3 Patient 4
Age (years) 67 68 66 45
Gender (M/F) M M M M
BMI on admission (kg/m²) 30,9 28,6 29,2 30,9
Blood group Comorbidities Obesity Diabetes Asthma Hypertension Prior liver disease Other
A negative Yes
No No No No pAF
B negative Yes
No No No No pAF
O positive Yes Yes No Yes No -
O positive Yes
No No No No - Mechanical ventilation (days)
54 91 74 57
Proning (yes/no) Yes Yes Yes Yes
Ketamine (yes/no) Yes Yes Yes Yes
Steroids Yes Yes Yes Yes
Antiviral medication No No Yes No
VV ECMO (days) 45 71 66 20
RRT (yes/no) Yes Yes Yes Yes
MARS (yes/no) No Yes No No
Sepsis episodes 3 4 6 2
ICU stay (days) 70 186 169 72
Liver Transplantation (yes/no)
Days after admission MELD score (listing) UNOS score (listing)
Yes 167 20
2
Yes 132 31
1
No - - -
No - - - Time of follow up (days)
Alive at last follow up
267 Yes
186 No
169 No
258 Yes
BMI: Body Mass Index; M: Male; F: Female; pAF: paroxysmal atrial fibrillation; MARS: Molecular Absorbent Recirculating System; RRT: Renal replacement therapy; VV ECMO: veno-venous extracorporeal membrane oxygenation; MELD: model for end-stage liver disease; UNOS: United Network for Organ Sharing.
Patient 1 suffered from intractable pruritus, recurrent cholangitis and encephalopathy, and received a liver transplant 25 weeks after admission. The postoperative course was uneventful with rapidly normalising liver tests and hospital discharge on postoperative day 40. Histology on the explant confirmed pretransplant biopsy findings. The patient is currently doing well. Patient 2 exhibited persistent refractory biliary sepsis, encephalopathy, necrotizing cholecystitis, and persistent renal failure. Following weaning from mechanical ventilation and improvement of encephalopathy after MARS treatment, he received a combined liver-kidney transplantation 22 weeks after admission. Cholestatic parameters normalized quickly, but multi-factorial acute kidney injury developed as well as multi-resistant Pseudomonas pneumonia, with a fatal outcome 6 weeks post-
transplant. Patient 3 died of haemorrhagic shock on day 169. Autopsy revealed massive lethal hepatic haemorrhage from unknown origin and severe cholestasis with dilated intrahepatic bile ducts and biliomas. In patient 4, cholestasis developed after resolution of ARDS and renal failure, and presented with mild elevation of gamma-glutamyltransferase and alkaline phosphatase levels but normal bilirubin levels. Cholestasis is currently resolved.
Supplementary Fig. 2 Histology
Representative image of histological findings from 1 out of 3 patients. A) Pre-transplant transjugular liver biopsy (haematoxylin-eosin staining, x100): the portal tract (upper left part) showed severe biliary epithelial injury with picnosis, irregular nuclei, intraepithelial lymphocytes, vacuolized cytoplasm and thickened basement membranes, suggesting secondary sclerosing cholangitis. Ductular bilirubinostasis was also present. The centrolobular parenchyma (lower left part) showed severe bilirubinostasis with foamy macrophages, as seen in biliary obstruction. B). Histology of an explant liver (haematoxylin-eosin staining, x50): a larger intrahepatic bile duct is seen with lithiasis, erosion of epithelium and purulent ascending cholangitis. Ductular bilirubinostasis was focally present.
