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Liver Allograft Failure After Nivolumab Treatment-A Case Report With Systematic Literature Research


Gassmann, Dimitri; Weiler, Stefan; Mertens, Joachim C; Reiner, Cäcilia S; Vrugt, Bart; Nägeli, Mirjam; Mangana, Joanna; Müllhaupt, Beat; Jenni, Fabienne; Misselwitz, Benjamin (2018). Liver Allograft Failure After Nivolumab Treatment-A Case Report With Systematic Literature Research. Transplantation Direct, 4(8):e376.

Abstract

Background Orthotopic liver transplantation (OLT) is a potential curative treatment in patients with hepatocellular carcinoma (HCC); however, treatment options for recurrent HCC after OLT are limited. Immune checkpoint inhibitors, such as nivolumab, an inhibitor of programmed cell death protein 1, have been successfully used for metastatic HCC but data on safety of nivolumab following solid organ transplantation are limited. Methods We report a 53-year-old woman with HCC who was treated with OLT. After 2 years, HCC recurred. Initial treatment with sorafenib was discontinued due to side effects and disease progression. Progressive HCC in the lung and lymph nodes was subsequently treated with nivolumab. One week after the first nivolumab dose, rapid progressive liver dysfunction was noted. Liver biopsy revealed severe cellular graft rejection prompting treatment with intravenous steroids and tacrolimus. Liver function continued to decline, leading to severe coagulopathy. The patient succumbed to intracranial hemorrhage. Results A systematic PubMed search revealed 29 cases treated with a checkpoint inhibitor following solid organ transplantation. Loss of graft was described in 4 (36%) of 11 cases with OLT and in 7 (54%) of 13 cases after kidney transplantation. However, cases with favorable outcome were also described. Eighteen cases with adverse events were identified upon searching the World Health Organization database VigiBase, including 2 cases with fatal outcome in liver transplant recipients due to graft loss. Conclusion Experience with checkpoint inhibitors in solid organ transplant recipients is limited. Published cases so far suggest severe risks for graft loss as high as 36% to 54%.

Abstract

Background Orthotopic liver transplantation (OLT) is a potential curative treatment in patients with hepatocellular carcinoma (HCC); however, treatment options for recurrent HCC after OLT are limited. Immune checkpoint inhibitors, such as nivolumab, an inhibitor of programmed cell death protein 1, have been successfully used for metastatic HCC but data on safety of nivolumab following solid organ transplantation are limited. Methods We report a 53-year-old woman with HCC who was treated with OLT. After 2 years, HCC recurred. Initial treatment with sorafenib was discontinued due to side effects and disease progression. Progressive HCC in the lung and lymph nodes was subsequently treated with nivolumab. One week after the first nivolumab dose, rapid progressive liver dysfunction was noted. Liver biopsy revealed severe cellular graft rejection prompting treatment with intravenous steroids and tacrolimus. Liver function continued to decline, leading to severe coagulopathy. The patient succumbed to intracranial hemorrhage. Results A systematic PubMed search revealed 29 cases treated with a checkpoint inhibitor following solid organ transplantation. Loss of graft was described in 4 (36%) of 11 cases with OLT and in 7 (54%) of 13 cases after kidney transplantation. However, cases with favorable outcome were also described. Eighteen cases with adverse events were identified upon searching the World Health Organization database VigiBase, including 2 cases with fatal outcome in liver transplant recipients due to graft loss. Conclusion Experience with checkpoint inhibitors in solid organ transplant recipients is limited. Published cases so far suggest severe risks for graft loss as high as 36% to 54%.

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Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Diagnostic and Interventional Radiology
04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:August 2018
Deposited On:25 Oct 2018 12:09
Last Modified:29 Nov 2018 08:50
Publisher:Lippincott Williams & Wilkins
ISSN:2373-8731
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1097/TXD.0000000000000814
PubMed ID:30255136

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