Severe Unresolved Cholestasis Due to Unknown Etiology Leading to Early Allograft Failure Within the First 3 Months of Liver Transplantation.

Angelico, Roberta and Gerlach, Undine A and Gunson, Bridget K and Neil, Desley A and Mergental, Hynek and Isaac, John and Muiesan, Paolo and Mirza, Darius F and Perera, M Thamara Pr (2018) Severe Unresolved Cholestasis Due to Unknown Etiology Leading to Early Allograft Failure Within the First 3 Months of Liver Transplantation. Transplantation, 102 (8). pp. 1307-1315. ISSN 1534-6080.

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Causes of severe cholestasis after liver transplantation (LT) are multi-factorial. Although the etiology is predictable in some, others culminate in graft/patient loss without a definitive cause identified. Severe cholestasis is usually associated with overlapped histological findings of rejection and biliary features, and diagnostic interpretation may pose a challenge.


This is 10-year retrospective analysis of patients with unexplained severe cholestasis resulting in death/graft loss within 90 days of LT. Of 1 583 LT during the study period, 90-day graft failure occurred in 129 (8%) cases; a total of 45 (3%) patients had unresolving severe cholestasis (bilirubin, >100 μmol/L; alkaline phosphatase, >400 UI/L after 15 days from LT), excluding those due to primary nonfunction/sepsis/vascular causes (n = 84). Demographics, allograft biopsies, radiological investigations, and clinical outcome were analyzed.


All patients had persistent abnormal liver biochemistry. Doppler ultrasound scan was normal in all cases. Thirty-five (78%) recipients had at least 1 allograft biopsy (2 [1-9]). On the first biopsy, 22 (63%) patients had acute rejection, 4 (18%) early-chronic rejection, 12 (34%) antibody-mediated rejection. In subsequent biopsies chronic rejection was evident in 5 (14%) cases. Donor-specific antibodies were detected in all patients tested. Biliary anatomy was studied in detail in 9 (20%) patients, all presenting biliary strictures. The majority (n = 39; 87%) died within 32 (10-91) days, only survivors were from retransplantation (n = 3;6.5%) and biliary intervention (n = 3;6.5%).


Unresolving severe cholestasis after LT is a key parameter predicting patient/allograft outcome. Histologically, rejection seems to overlap with biliary strictures; hence, allograft biopsy with signs of rejection should not be a reason to overlook biliary problems, in particular when biliary features are present. Only extensive radiological investigation/intervention or retransplantation prevents patient/allograft loss.

Item Type: Article
Subjects: WI Digestive system. Gastroenterology
Divisions: Planned IP Care > Gastroentrology
Related URLs:
Depositing User: Mrs Semanti Chakraborty
Date Deposited: 01 Apr 2019 10:00
Last Modified: 01 Apr 2019 10:00

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