From the Guidelines
Liver rejection in transplant patients should be diagnosed and treated promptly to prevent graft loss and improve patient outcomes, with the most recent and highest quality evidence suggesting that tacrolimus is the preferred immunosuppressive agent due to its efficacy in reducing mortality, graft loss, and rejection rates 1.
Diagnostic Criteria
Liver rejection is diagnosed through a combination of clinical symptoms, laboratory tests, and liver biopsy findings. Patients may present with fever, abdominal pain, jaundice, and elevated liver enzymes (AST, ALT, alkaline phosphatase, and bilirubin). The definitive diagnosis requires a liver biopsy, which typically shows portal inflammation, bile duct damage, and endotheliitis in acute cellular rejection.
Treatment Options
Treatment depends on rejection severity but primarily involves intensifying immunosuppression. For mild to moderate acute rejection, high-dose corticosteroids are the first-line treatment, typically methylprednisolone 500-1000mg daily for 3 days, followed by a prednisone taper. If rejection persists, thymoglobulin (1.5mg/kg/day for 5-7 days) or increased doses of tacrolimus (targeting trough levels of 8-12 ng/mL) or cyclosporine (targeting trough levels of 200-300 ng/mL) may be used.
- Key considerations in treatment include:
- The use of tacrolimus as the primary immunosuppressive agent due to its proven efficacy in reducing mortality and graft loss 1.
- The potential benefits and risks of using generic formulations of immunosuppressive drugs, with a need for stringent therapeutic drug monitoring during the initial switch phase 1.
- The importance of monitoring for medication side effects, such as hyperglycemia, hypertension, and renal dysfunction, particularly with the use of calcineurin inhibitors like tacrolimus and cyclosporine 1.
Post-Treatment Follow-Up
Post-treatment follow-up should include frequent liver function tests to monitor response, with repeat biopsy if clinical improvement is not observed within 3-5 days. Prophylactic antimicrobial coverage should be considered during high-dose immunosuppression to prevent opportunistic infections.
- Ongoing monitoring and adjustment of immunosuppressive therapy are crucial to balance the risk of rejection with the potential side effects of immunosuppression, with the goal of optimizing patient outcomes and quality of life.
From the Research
Diagnostic Criteria for Liver Rejection
- Liver biopsy remains the current standard of care for diagnosing rejection in liver transplant patients 2, 3, 4
- However, biopsy has its limitations, including physical and economic burden to the patient, and diagnostic limitations 2
- Non-invasive diagnostic techniques, such as biomarkers and molecular diagnostics, are being explored to improve upon the current standard of care 2, 3, 5
- Biomarkers, such as dd-cfDNA, DSA, mRNA microarray profiling, and cytokine responses, show potential in indicating the status of allograft rejection and aiding in immunosuppression modulation 3, 5
Treatment Options for Liver Rejection
- Acute rejection generally improves with steroid boluses, and steroid-resistant rejection is uncommon 6
- Chronic rejection (CR) may improve with escalation of immunosuppression or may result in irreversible loss of graft function leading to retransplantation or death 6
- Proper classification of rejection type and severity is imperative, as this guides management and ultimately graft preservation 4
- Future areas of promise include non-invasive testing for detection of rejection to reduce the morbidity associated with invasive testing and further advances in immunosuppression management to reduce toxicities associated with immunosuppression while minimizing rejection-related morbidity 4
Biomarkers for Liver Rejection
- Several promising biomarkers exist in the field of liver transplant rejection, including blood genomic assays measuring miRNA, mRNA, and donor-derived cell-free DNA 5
- Serum levels of cytokines, proteoforms, donor-specific antibodies, and immunophenotyping have shown promising results in predicting rejection pre- and/or post-transplant 5
- Biomarkers represent a novel method of predicting the risk of developing allograft rejection and may improve patient management, reduce complications from over- or under-immunosuppression, and ultimately enhance outcomes 5