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

Roberta Angelico, Undine A Gerlach, Bridget K Gunson, Desley Neil, Hynek Mergental, John Isaac, Paolo Muiesan, Darius Mirza, M Thamara Pr Perera

Research output: Contribution to journalArticle

Abstract

BACKGROUND: 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.

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, >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.

RESULTS: 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%).

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 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.

Original languageEnglish
Pages (from-to)1307-1315
Number of pages9
JournalTransplantation
Volume102
Issue number8
DOIs
Publication statusPublished - Aug 2018

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Cholestasis
Liver Transplantation
Allografts
Biopsy
Transplants
Pathologic Constriction
Doppler Ultrasonography
Antibodies
Bilirubin
Biochemistry
Alkaline Phosphatase
Blood Vessels
Survivors
Anatomy
Sepsis
Demography
Tissue Donors
Liver

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Severe Unresolved Cholestasis Due to Unknown Etiology Leading to Early Allograft Failure Within the First 3 Months of Liver Transplantation. / Angelico, Roberta; Gerlach, Undine A; Gunson, Bridget K; Neil, Desley; Mergental, Hynek; Isaac, John; Muiesan, Paolo; Mirza, Darius; Perera, M Thamara Pr.

In: Transplantation, Vol. 102, No. 8, 08.2018, p. 1307-1315.

Research output: Contribution to journalArticle

Angelico, R, Gerlach, UA, Gunson, BK, Neil, D, Mergental, H, Isaac, J, Muiesan, P, Mirza, D & Perera, MTP 2018, 'Severe Unresolved Cholestasis Due to Unknown Etiology Leading to Early Allograft Failure Within the First 3 Months of Liver Transplantation', Transplantation, vol. 102, no. 8, pp. 1307-1315. https://doi.org/10.1097/TP.0000000000002139
Angelico, Roberta ; Gerlach, Undine A ; Gunson, Bridget K ; Neil, Desley ; Mergental, Hynek ; Isaac, John ; Muiesan, Paolo ; Mirza, Darius ; Perera, M Thamara Pr. / Severe Unresolved Cholestasis Due to Unknown Etiology Leading to Early Allograft Failure Within the First 3 Months of Liver Transplantation. In: Transplantation. 2018 ; Vol. 102, No. 8. pp. 1307-1315.
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title = "Severe Unresolved Cholestasis Due to Unknown Etiology Leading to Early Allograft Failure Within the First 3 Months of Liver Transplantation",
abstract = "BACKGROUND: 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.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, >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.RESULTS: 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{\%}).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 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.",
author = "Roberta Angelico and Gerlach, {Undine A} and Gunson, {Bridget K} and Desley Neil and Hynek Mergental and John Isaac and Paolo Muiesan and Darius Mirza and Perera, {M Thamara Pr}",
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T1 - Severe Unresolved Cholestasis Due to Unknown Etiology Leading to Early Allograft Failure Within the First 3 Months of Liver Transplantation

AU - Angelico, Roberta

AU - Gerlach, Undine A

AU - Gunson, Bridget K

AU - Neil, Desley

AU - Mergental, Hynek

AU - Isaac, John

AU - Muiesan, Paolo

AU - Mirza, Darius

AU - Perera, M Thamara Pr

PY - 2018/8

Y1 - 2018/8

N2 - BACKGROUND: 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.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, >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.RESULTS: 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%).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 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.

AB - BACKGROUND: 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.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, >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.RESULTS: 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%).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 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.

U2 - 10.1097/TP.0000000000002139

DO - 10.1097/TP.0000000000002139

M3 - Article

C2 - 29470351

VL - 102

SP - 1307

EP - 1315

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 8

ER -