What is the treatment for liver rejection?

From the Guidelines

Treatment for liver rejection involves a combination of immunosuppressive medications, with tacrolimus being the preferred calcineurin inhibitor due to its ability to reduce mortality and graft loss compared to cyclosporine 1. The standard approach begins with high-dose corticosteroids like methylprednisolone for acute rejection episodes. Maintenance immunosuppression usually includes a calcineurin inhibitor (tacrolimus), an antimetabolite (mycophenolate mofetil), and low-dose prednisone. Some key points to consider in the treatment of liver rejection include:

• The use of tacrolimus trough levels should be kept at 6-10 ng/ml during the first month followed by 4-8 ng/ml thereafter 1
• Combining tacrolimus with other immunosuppressive drugs (MMF, AZA or mTORi) to allow for a lower range of tacrolimus trough levels than recommended for monotherapy and to help preserve renal function 1
• 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 minimised by employing combined immunosuppressive regimens, preferably an mTORi in the case of high risk of hepatic or extrahepatic cancer recurrence 1 For steroid-resistant rejection, stronger agents like antithymocyte globulin (ATG) or monoclonal antibodies such as basiliximab may be used. Some of the benefits of using these medications include:
• Reduced incidence of acute rejection
• Lower risk of graft loss
• Improved patient survival
• Minimized risk of renal dysfunction However, it is essential to carefully monitor drug levels to balance preventing rejection with avoiding toxicity and infection risks. Treatment adjustments are made based on the severity of rejection determined by liver biopsy findings, liver function tests, and the patient's overall condition. Early detection through regular blood tests is crucial for successful treatment, as chronic rejection is more difficult to reverse. Patients must adhere strictly to their medication regimen and follow up regularly with their transplant team to monitor for signs of rejection or medication side effects. In addition to medication, lifestyle modifications such as a healthy diet, regular exercise, and avoiding alcohol consumption can help prevent recurrent or de novo metabolic disorders after liver transplantation. Regular screening for alcohol biomarkers and addressing metabolic risk factors can also help prevent recurrent or de novo metabolic disorders. Adjustment of immunosuppression should be considered according to the kind of associated complication but should be balanced against the risk of rejection 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.

The treatment for liver rejection is tacrolimus in combination with other immunosuppressants, as it is indicated for the prophylaxis of organ rejection in adult and pediatric patients receiving allogeneic liver transplants 2.

• The recommended initial oral dosage for liver transplant patients is 0.1 to 0.15 mg/kg/day capsules, divided in two doses, every 12 hours, with a whole blood trough concentration range of 5 to 20 ng/mL for the first year after transplant 2.
• For pediatric liver transplant patients, the initial oral dosage is 0.15 to 0.2 mg/kg/day capsules, divided in two doses, every 12 hours, with a whole blood trough concentration range of 5 to 20 ng/mL for the first year after transplant 2.

From the Research

Treatment for Liver Rejection

The treatment for liver rejection typically involves the use of immunosuppressive medications to reduce the immune system's attack on the transplanted liver.

• The most commonly used treatment is intravenous methylprednisolone, a high-dose steroid regimen 3.
• The optimal dose and duration of the steroid regimen may vary, with some studies suggesting that a 6-day taper from 200 to 20 mg/d is more effective and safer than a 3-day course of 1,000 mg of methylprednisolone 3.
• In cases where patients develop an allergic reaction to intravenous methylprednisolone, alternative treatments such as dexamethasone may be used 4.

Steroid-Resistant Acute Rejections

In some cases, liver transplant recipients may experience steroid-resistant acute rejections, which can be treated with antithymocyte globulin 5.

• This treatment has been shown to be effective in 83.3% of patients with steroid-resistant acute rejection, with minimal adverse effects 5.
• The use of antithymocyte globulin as a therapeutic option for steroid-resistant acute rejection is supported by studies, which highlight its acceptable adverse effects and effectiveness in treating this condition 5.

Acute and Chronic Rejection

Acute and chronic rejection are significant clinical concerns in liver transplant recipients, with acute rejection generally improving with steroid boluses and steroid-resistant rejection being uncommon 6.

• Chronic rejection may improve with escalation of immunosuppression or may result in irreversible loss of graft function, leading to retransplantation or death 6.
• The incidence of acute and chronic rejection has declined in recent years due to improved immunosuppressive regimens 6.

Incidence and Treatment of Acute Rejection

The incidence of acute rejection varies, with one study reporting that 33.5% of patients experienced acute rejection episodes 7.

• High-doses of steroids have been shown to be effective in treating acute rejection, with no significant difference in liver function tests between patients treated with lower versus higher doses of methylprednisolone 7.
• Recurrence of acute rejection is more common in patients treated with lower doses of methylprednisolone 7.