Severe unresolved cholestasis due to unknown aetiology leading to early allograft failure within the first 3 months of liver transplantation

ABSTRACTBackgroundCauses of severe cholestasis following liver transplantation(LT) are multi-factorial; whilst the aetiology 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.MethodsThis 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 >100μmol/L and ALP >400UI/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 analysed.ResultsAll patients had persistent abnormal liver biochemistry. Doppler-US 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 re-transplantation(n=3;6.5%) and biliary intervention(n=3;6.5%).ConclusionsUnresolving 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 shouldn't be a reason to overlook biliary problems, in particular when biliary features are present. Only extensive radiological investigation/intervention or re-transplantation prevents patient/allograft loss. Background Causes of severe cholestasis following liver transplantation(LT) are multi-factorial; whilst the aetiology 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. Methods 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 >100μmol/L and ALP >400UI/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 analysed. Results All patients had persistent abnormal liver biochemistry. Doppler-US 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 re-transplantation(n=3;6.5%) and biliary intervention(n=3;6.5%). Conclusions 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 shouldn't be a reason to overlook biliary problems, in particular when biliary features are present. Only extensive radiological investigation/intervention or re-transplantation prevents patient/allograft loss. Correspondence: Mr. Thamara Perera, FRCS, Consultant Surgeon, Liver Unit, Queen Elizabeth hospital Birmingham, Edgbaston, Birmingham B15 2TH, United kingdom. E-mail: Thamara.Perera@uhb.nhs.uk AUTHORSHIP: – Roberta Angelico - Data collection, analysis and interpretation, wrote the manuscript – Undine A Gerlach - Data collection, analysis and interpretation, wrote the manuscript – Bridget Gunson - Data collection, analysis and interpretation – Desley Neil - Data collection, review of allograft biopsies, analysis, intellectual content – Hynek Mergental - Data collection, analysis and interpretation – John R Isaac - Data collection, analysis and interpretation, intellectual content – Paolo Muiesan - Data collection, analysis and interpretation, intellectual content – Darius F Mirza - Conceptualised the study, data interpretation, intellectual content – M Thamara PR Perera - Designed the study, data analysis and interpretation, intellectual content DISCLOSURE: The authors declare no conflicts of interest. FUNDING: BKG, HM, DFM are supported by the NIHR Birmingham Biomedical Research Centre. Copyright © 2018 Wolters Kluwer Health, Inc. 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