Sirolimus (SRL) provides effective immunosuppression for kidney transplantation and may be useful in patients with delayed allograft function after kidney transplantation. We review our experience with SRL in liver transplant recipients for whom calcineurin inhibitors are undesirable. Fourteen patients with renal insufficiency or acute mental status impairment were administered SRL after liver transplantation (5-to 10-mg load, 1 to 4 mg/d). Immunosuppression also consisted of mycophenolate mofetil and corticosteroids. On resolution of neurological or renal dysfunction (return to baseline mental status or serum creatinine level), tacrolimus (TAC) therapy was initiated. Twelve patients received primary transplants, 1 patient received a combined liver-kidney transplant, and 1 patient received a third transplant. C urrently, calcineurin inhibitors are the mainstay drugs in regimens to prevent acute rejection in liver transplantation. In the past decade, the efficacy of calcineurin inhibitors has revolutionized solid-organ transplantation. However, both cyclosporine and tacrolimus are limited by their toxicities, most prominently nephrotoxicity and neurotoxicity. Unfortunately, both renal dysfunction and encephalopathy are often prominent features in the clinical presentation of many liver transplant recipients before transplantation. In these patients, the management of posttransplantation immunosuppression is particularly challenging because of the need to provide adequate immunosuppression without exacerbating renal dysfunction or causing neurotoxicity. In this setting, calcineurin inhibitors are often withheld, which may result in an increased risk for allograft rejection.Sirolimus (SRL; rapamycin; Wyeth-Ayerst, Philadelphia, PA), a macrocyclic lactone produced by Streptomyces hygroscopicus, has been shown to be a potent therapeutic agent in combination with cyclosporine (CsA). It resembles tacrolimus (TAC; Prograf; Fujisawa Healthcare, Deerfield, IL) structurally and binds the same immunophilin FK506 12-kd binding protein . Whereas CsA and TAC inhibit interleukin-2 gene transcription, SRL acts by blocking postreceptor signal transduction and interleukin-2-dependent proliferation. 1 SRL has been shown to be a powerful immunosuppressant in in vitro and animal models. 2,3 More recently, used in combination with CsA, it has been shown to be a potent therapeutic antirejection agent for kidney transplantation in humans. 4 The side-effect profile of SRL differs from that of the calcineurin inhibitors. Notably, no nephrotoxicity or neurotoxicity has been observed; however, leukopenia, thrombocytopenia, hypertriglyceridemia, and hypercholesterolemia have been noted. 5 We and others have used SRL in combination with anti-CD25 monoclonal antibody induction in a calcineurin-inhibitorsparing regimen for renal transplant recipients with delayed or impaired initial graft function. When therapeutic dosages of SRL were administered and titrated to maintain serum trough levels greater than 8 to

We conclude that a very short course of HBIG combined with long-term antiviral therapy is highly effective in preventing HBV recurrence and should be the preferred strategy for LT recipients with undetectable or low-level viremia at time of LT.

Patients receiving zafirlukast may develop severe liver injury and should be observed for signs and symptoms of hepatitis.

Latent tuberculosis infection is an important problem for solid organ transplant recipients because of the frequency of its occurrence and its potential for reactivation. Because of the high mortality rate associated with active tuberculosis infections in transplant recipients, guidelines from the American Thoracic Society recommend treatment for latent tuberculosis in this population. However, the choice of treatments is often difficult because liver transplant recipients may be more sensitive to isoniazid hepatotoxicity, and rifampin has significant drug interactions with the calcineurin inhibitors used for immunosuppression. Two prior case reports described success with the use of rifabutin, a rifampin alternative, as part of a multidrug treatment regimen for active tuberculosis in posttransplant patients; however, there is no prior literature describing any experience with rifabutin for the treatment of latent tuberculosis in the posttransplant setting. We present a summary of tacrolimus drug levels and corresponding dose requirements for a single posttransplant patient during the administration of 3 different latent tuberculosis drug regimens: rifampin alone, rifampin plus ketoconazole, and rifabutin. In this patient's case, rifabutin allowed the maintenance of adequate tacrolimus levels, although an approximate 2.5‐fold increase in the dose was required. Rifampin alone was associated with inadequate immunosuppressant levels, and rifampin plus ketoconazole was associated with a problematically prolonged QT interval and concerns about inadequate tuberculosis treatment. Liver Transpl 19:457–461, 2013. © 2013 AASLD.