Safety and Efficacy of Liposomal Amphotericin B for Patients With Invasive Mold Diseases in Liver Transplant Recipients

Invasive Mold Diseases

Invasive mold diseases (IMD) carry extremely high mortality rates in liver transplant recipients (aspergillosis prevalence \ 1.8%, mortality 60%-90%; mucormycosis prevalence \ 2%, mortality 38%-95%). Guidelines emphasize early antifungal therapy: liposomal amphotericin B (L-AmB) is the first-line choice in liver insufficiency; voriconazole remains the gold standard for aspergillosis (but ineffective against mucormycosis), yet its use is limited by significant drug-drug interactions-requiring a 50%-60% dose reduction of calcineurin inhibitors and contraindicated with sirolimus-thereby increasing the risk of graft rejection. Currently, no head-to-head clinical trials compare voriconazole and L-AmB in liver transplant recipients with IMD. Therefore, a prospective real-world study is planned to generate robust data to support updates to international or Chinese guidelines.

Invasive mold diseases (IMD) represent a significant cause of morbidity and mortality among solid organ transplant (SOT) recipients. Liver transplant recipients are at heightened risk for developing IMD due to complex biliary-enteric anastomosis and underlying immunological deficits associated with liver dysfunction and the need for immunosuppressive therapy. Among SOT patients, invasive aspergillosis is the second most common invasive fungal infection and poses a substantial mortality risk, especially for those who have undergone liver transplantation. Current research indicates that 1.8% of liver transplant recipients develop invasive aspergillosis, with mortality rates reported between 60% and 90%. While mucormycosis is less prevalent than invasive aspergillosis-accounting for approximately 2% of fungal infections in SOT recipients-it is associated with a poor prognosis, with mortality rates ranging from 38% to 95% in this population. These statistics highlight the critical need for effective antifungal therapies in the management of IMD among liver transplant patients. Guidance from the 2019 American Society of Transplantation Infectious Diseases Community of Practice (ASTIDCOP) underscores the importance of early antifungal therapy initiation to optimize outcomes for SOT recipients affected by invasive aspergillosis. The primary antifungal drug classes used for treating invasive aspergillosis include polyenes, triazoles, and echinocandins. In the context of liver insufficiency, liposomal amphotericin B (L-AmB) is typically considered the first-line therapeutic option. For mucormycosis, the 2019 guidelines from the European Confederation of Medical Mycology (ECMM) and the Mycoses Study Group Education and Research Consortium (MSGERC) recommend liposomal amphotericin B (L-AmB) as the first-line treatment. However, there are currently no international guidelines specifically addressing the management of mucormycosis in solid organ transplant recipients. Voriconazole remains the preferred agent for treating invasive aspergillosis and is considered the standard of care. Lipid formulations of L-AmB are regarded as alternative treatment options for invasive aspergillosis. However, voriconazole is not recommended for the treatment of mucormycosis. Although voriconazole, a triazole antifungal agent, offers broad-spectrum activity against various yeast and mold species and is the current gold standard for invasive aspergillosis, its use is constrained by drug-drug interactions and safety concerns. Liver function has a significant impact on the pharmacokinetics of antifungal agents, which is particularly relevant in liver transplant recipients. Both cyclosporine and tacrolimus are extensively metabolized by CYP3A4 and CYP3A5, necessitating a 50% to 60% reduction in the dosage of these calcineurin inhibitors when administered with voriconazole. The coadministration of voriconazole with sirolimus is contraindicated. Reducing the dose of immunosuppressive agents may increase the risk of graft rejection, presenting a therapeutic challenge in this patient population. No direct head-to-head clinical trials have compared voriconazole and AmBisome for treating invasive mold infections in liver transplant recipients, especially regarding adverse reactions. This prospective, bigger scale, real-world study aims to fill the gap by evaluating both drugs such as IMD patients with liver transplantation to facilitate robust scientific data support for updated international or Chinese guideline

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