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Chronic Rejection and Late Allograft Hepatitis

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Pediatric Hepatology and Liver Transplantation

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Abstract

Liver transplantation (LTx) in children is highly successful with >80% surviving 20 years. Most paediatric liver diseases are curable with LTx, and it is important to establish the long-term outcome to ensure that long-term survivors will have a normal life expectancy or to identify whether there will be a gradual decline in liver function and eventual graft loss.

The main causes of late graft dysfunction are multifactorial and include infection; acute or chronic rejection; recurrent disease; immunological injury such as de novo autoimmune hepatitis, idiopathic posttransplant hepatitis, and graft fibrosis; and technical complications such as late portal vein thrombosis, late hepatic artery thrombosis, and biliary strictures.

De novo autoimmune hepatitis (“plasma cell hepatitis”, “immune-mediated graft hepatitis”) is an immune-mediated disease similar to autoimmune hepatitis in the native liver. Diagnosis is based on graft dysfunction with elevated IgG and positive non-specific autoantibodies. Most children respond to prednisolone and azathioprine with a good outcome.

Serial protocol liver biopsies after transplantation have demonstrated the gradual development of unexplained graft inflammation (“idiopathic” posttransplant hepatitis, IPTH) and graft fibrosis in biopsies obtained >12 months post-LT in children with good graft function and (near) normal liver biochemistry.

Although the clinical significance of these findings is uncertain, it is possible that IPTH may be a form of rejection or chronic antibody-mediated rejection as it is associated with the presence of auto-/alloantibodies, de novo class II donor-specific HLA antibodies (DSA), and previous episodes of rejection and may improve or be prevented with increased immunosuppression.

This chapter will focus on the diagnosis and management of de novo autoimmune hepatitis, idiopathic posttransplant hepatitis, and graft fibrosis and potential mechanisms for their development.

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Authors and Affiliations

  1. The Liver Unit, Birmingham Womens and Childrens Hospital and University of Birmingham, Birmingham, UK

    Deirdre Kelly

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Correspondence to Deirdre Kelly .

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  1. Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII Bergamo, Bergamo, Italy

    Lorenzo D'Antiga

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Kelly, D. (2019). Chronic Rejection and Late Allograft Hepatitis. In: D'Antiga, L. (eds) Pediatric Hepatology and Liver Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-319-96400-3_33

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  • DOI: https://doi.org/10.1007/978-3-319-96400-3_33

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