What is the treatment for liver transplant rejection?

From the Guidelines

The treatment for liver transplant rejection involves immunosuppressive medications, with tacrolimus being the preferred calcineurin inhibitor due to its reduced mortality and graft loss rates compared to cyclosporine, as shown in a meta-analysis including 3813 patients 1. The standard approach includes a combination of calcineurin inhibitors, antimetabolites, and corticosteroids.

• For acute rejection episodes, high-dose methylprednisolone is administered intravenously, followed by a tapering dose of oral prednisone.
• In steroid-resistant cases, antithymocyte globulin (ATG) or monoclonal antibodies like basiliximab may be used.
• Long-term maintenance therapy usually consists of tacrolimus, with target blood levels of 6-10 ng/ml during the first month, followed by 4-8 ng/ml thereafter, as recommended by the EASL clinical practice guidelines 1.
• Mycophenolate mofetil is also used in combination with tacrolimus to allow for lower tacrolimus trough levels and to help preserve renal function. Regular blood tests are essential to monitor liver function and medication levels, with adjustments made based on rejection signs and side effects.
• These medications work by suppressing T-cell activation and proliferation, which are key components of the rejection process.
• Patients must adhere strictly to their medication regimen and attend all follow-up appointments to ensure graft survival and manage potential complications. The administration of basiliximab induction with delayed introduction of tacrolimus is strongly recommended in patients at risk of developing post-transplant renal dysfunction 1.
• Exposure to CNIs should be minimized by employing combined immunosuppressive regimens, preferably an mTORi in the case of high risk of hepatic or extrahepatic cancer recurrence.
• An mTORi-based immunosuppression regimen is strongly recommended in patients with a history of recurrent/de novo non-melanoma skin cancer 1.

From the FDA Drug Label

Tacrolimus capsule is a calcineurin-inhibitor immunosuppressant indicated for the prophylaxis of organ rejection in adult patients receiving allogeneic liver, kidney, or heart transplants and pediatric patients receiving allogeneic liver transplants in combination with other immunosuppressants. Mycophenolate mofetil is indicated for the prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac or hepatic transplants.

The treatment for liver transplant rejection is the use of immunosuppressants such as:

• Tacrolimus in combination with other immunosuppressants
• Mycophenolate mofetil concomitantly with cyclosporine and corticosteroids 2, 2, 3.

From the Research

Treatment for Liver Transplant Rejection

The treatment for liver transplant rejection typically involves the use of immunosuppressive medications to reduce the immune system's response and prevent damage to the transplanted liver.

• Intravenous methylprednisolone is commonly used as first-line therapy for acute hepatic cellular rejection in liver transplant recipients 4.
• The optimal dose and duration of steroid treatment may vary, with some studies suggesting that a 6-day taper from 200 to 20 mg/d after an initial intravenous dose of 1,000 mg of methylprednisolone may be more effective and safer than other regimens 4.
• In cases of steroid-resistant acute rejection, antithymocyte globulin may be used as a therapeutic option, with a reported success rate of 83.3% in one study 5.

Immunosuppressive Regimens

Different immunosuppressive regimens may be used to prevent liver transplant rejection, including:

• Tacrolimus-based immunosuppressive therapy, which may be used in combination with other medications such as mycophenolate mofetil and steroids 5, 6.
• Prednisone avoidance may be effective in certain patients, particularly when used in combination with other immunosuppressants such as tacrolimus and everolimus 7.
• Thymoglobulin induction may be used in some cases, although its long-term efficacy and tolerability may vary 6.

Corticosteroid Withdrawal

Corticosteroid withdrawal may be attempted in patients with liver transplant, particularly those with autoimmune hepatitis, as it may be associated with a reduction in metabolic complications and improved liver function 8.

• However, corticosteroid withdrawal should be done cautiously and under close monitoring, as it may increase the risk of acute rejection in some patients 8.