Treatment of Rejection Post Liver Transplantation

Introduction to Rejection Treatment

The American Society of Transplantation recommends that acute cellular rejection after liver transplantation should be treated with increased immunosuppression, primarily high-dose corticosteroids, while chronic rejection requires intensification of baseline immunosuppression regimens and may necessitate retransplantation in cases with significant allograft dysfunction 1, 2

Approximately 15-30% of liver transplant recipients develop one or more episodes of acute cellular rejection, which typically occurs within the first 3 months post-transplantation but can occur at any time, according to the American Association for the Study of Liver Diseases 3, 1
Rejection is often suspected by hepatocellular abnormalities on liver function tests, but can also present with cholestatic patterns, as noted by the American Society of Transplantation 1
Liver biopsy remains the gold standard for definitive diagnosis of rejection, as stated by the European Association for the Study of the Liver 2, 4

High-dose corticosteroids are the first-line treatment for acute cellular rejection, as recommended by the American College of Gastroenterology 4
Standard protocol involves intravenous methylprednisolone boluses followed by a steroid taper, according to the American Society of Transplantation 1

Chronic rejection can be effectively treated only in early cases and may lead to graft loss if advanced, as noted by the European Association for the Study of the Liver 3
Treatment options include increasing calcineurin inhibitor (CNI) levels, as recommended by the American Society of Transplantation 1
Addition of mTOR inhibitors (sirolimus/everolimus) to baseline immunosuppression can also be effective, according to the American Society of Transplantation 1

Calcineurin inhibitor (CNI)-based immunosuppression is the cornerstone of immunosuppressive regimens in liver transplantation, as stated by the European Association for the Study of the Liver 5
Tacrolimus results in better long-term graft and patient survival than cyclosporine, according to the European Association for the Study of the Liver 5
Complete withdrawal of immunosuppression should not be attempted as standard care, even after an extended rejection-free period, as recommended by the European Association for the Study of the Liver 2

Monitoring for donor-specific antibodies (DSAs) may help identify patients at risk of antibody-mediated rejection, as noted by the European Association for the Study of the Liver 2
CMV viremia is a risk factor for chronic rejection, according to the American Society of Transplantation 1

The rate of graft loss due to ductopenic rejection has significantly decreased to less than 2% with modern immunosuppression regimens, as reported by the European Association for the Study of the Liver 3

Antibody-mediated rejection (AMR) may require plasmapheresis and/or intravenous immunoglobulin in addition to standard rejection treatment, as recommended by the European Association for the Study of the Liver 2
For persistent AMR not responding to first-line therapy, rituximab (to deplete B cells) or eculizumab (to inhibit complement activation) can be considered, according to the European Association for the Study of the Liver 2