What are the treatment options for COVID-19 in patients who have undergone liver transplantation (Orthotopic Liver Transplantation, OLT)?

From the Guidelines

Liver transplant recipients with COVID-19 should be prioritized for vaccination, and a third dose of the mRNA-1273 (Moderna) vaccine may be necessary to achieve adequate immunity, as evidenced by a recent randomized placebo-controlled trial 1. When managing COVID-19 in liver transplant recipients, it is crucial to consider their immunosuppressed state and the potential for drug interactions with immunosuppressive agents.

• For mild COVID-19, nirmatrelvir/ritonavir (Paxlovid) or remdesivir can be used, with careful adjustment of immunosuppressant medications.
• For moderate to severe disease, dexamethasone and remdesivir are recommended.
• Immunosuppression management is critical, with potential dose reductions of calcineurin inhibitors and mycophenolate mofetil.
• Vaccination is essential for prevention, and liver transplant recipients should be monitored for both COVID-19 progression and signs of organ rejection. The management of liver transplant recipients with COVID-19 requires a specialized approach that balances treating the viral infection while protecting the transplanted organ, as outlined in recent position statements 1. Key considerations include:
• Drug-drug interactions between COVID-19 therapies and immunosuppressive agents
• Potential prolongation of viral shedding due to immunosuppression
• Need for careful monitoring and adjustment of immunosuppressant medications
• Importance of vaccination in preventing COVID-19 in this vulnerable population.

From the FDA Drug Label

Perform hepatic laboratory testing in all patients before starting VEKLURY and while receiving VEKLURY as clinically appropriate The FDA drug label does not answer the question.

From the Research

Liver Transplant and COVID-19 Treatment

• The management of immunosuppression in liver transplant patients during the COVID-19 pandemic is crucial, and experiences with other viral infections suggest that management of immunosuppression without mycophenolate mofetil or m-Tor inhibitors may be beneficial 2.
• It is also important to pay attention to possible drug interactions, especially in the case of tacrolimus, with some of the treatments with antiviral effect given in the context of COVID-19 2.
• The immunosuppressive effect of immunomodulating drugs administered to patients with severe lung disease should be taken into account 2.

Clinical Best Practice Advice

• The American Association for the Study of Liver Diseases (AASLD) has provided guidance for hepatologists and liver transplant providers during the COVID-19 pandemic, including recommendations for the management of immunosuppression and the treatment of COVID-19 in liver transplant patients 3.
• The guidance emphasizes the importance of minimizing the impact of the COVID-19 pandemic on liver patients and healthcare providers, and provides a template for the development of clinical recommendations and policies 3.

COVID-19 in Liver Transplant Recipients

• Studies have shown that liver transplant recipients with COVID-19 are at risk of severe disease and mortality, and that the management of immunosuppression is critical in these patients 4, 5.
• The use of hydroxychloroquine and azithromycin has been reported in the treatment of COVID-19 in liver transplant recipients, but the efficacy and safety of these treatments are uncertain 4.
• The reduction of immunosuppression is not advised in patients with positive PCR test but not showing clinical signs, but the discontinuation of mycophenolate or mTOR inhibitors is recommended in patients with gastrointestinal or respiratory signs with fever 5.

Special Care of Liver Transplant Recipients

• The special care of liver transplant recipients diagnosed with COVID-19 requires careful consideration of the management of immunosuppression, the treatment of COVID-19, and the prevention of complications such as thrombosis and hyperinflammatory syndrome 5, 6.
• The use of lopinavir/ritonavir should be avoided due to severe drug interactions with calcineurin inhibitors, and the efficacy and tolerability of hydroxychloroquine remains uncertain 5.
• Early thromboprofilaxis combination with low-molecular-weight heparin and low-dose aspirin is strongly recommended, and the maintenance of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II-receptor blocker (ARB) therapy is advised when they were prescribed earlier 5.