Ab initio calcineurin inhibitor-based monotherapy immunosuppression after liver transplantation reduces the risk for Pneumocystis jirovecii pneumonia.

At the Tor Vergata University of Rome, ab initio calcineurin inhibitor-based monotherapy immunosuppression (IS) is the standard of treatment after liver transplantation (LT). As the net state of IS determines the onset of Pneumocystis jirovecii pneumonia (PCP), we hypothesized that, in the presence of weak impairment of the immune function, as determined by the above-mentioned IS, the host is not overexposed to the risk for PCP and consequently the specific anti-PCP prophylaxis is unnecessary. In a single-cohort descriptive study, we retrospectively investigated the incidence of PCP in 203 LT patients who did not receive anti-PCP prophylaxis because they were under monotherapy IS. The primary endpoint of the study was the incidence of PCP during the first 12 months following LT; secondary endpoints were the incidence of acute rejection requiring additional IS and of CMV infection. No cases of PCP were recorded. The incidence of CMV and acute rejection was 3.9% and 0.9%, respectively. Our data suggest that monotherapy IS after LT may nullify the risk for PCP even in the absence of any specific prophylaxis.

Clinical operational tolerance after kidney transplantation: a short literature review.

The clinical era of solid organ transplantation started with a renal transplantation (RT) performed between identical twins in Boston in 1954. The patient did not receive any immunosuppression, thus representing the very first case of operational tolerance (Tol). However, more than half a century later, we must admit the inadequacy of our knowledge regarding such a fundamental aspect of transplant immunology, as demonstrated by the fact that Tol has never been achieved in an intention-to-treat protocol. Herein we aim to shortly review the worldwide experience on clinical operational Tol after RT. Thus far, reports on successful cases of Tol after RT have been anecdotal: the largest series included no more than 10 individuals. We will understand that Tol can develop even in the presence of either HLA mismatches or blood group incompatibility at baseline, in the presence of anti-HLA antibodies during follow-up, as well as in patients having experienced acute rejection. Despite the lack of robust evidence, the fact that Tol is often accidentally discovered by transplant physicians during follow-up in noncompliant patients justifies the hypothesis that the real number of Tol cases might be much higher than currently reported.

The role of liver transplantation in the treatment of hereditary hemorrhagic telangiectasia: a short literature review.

The liver is involved in up to 73% of patients suffering from hereditary hemorrhagic telangiectasia (HHT), but only some of them become symptomatic. Although management is often conservative, sometimes a more aggressive approach is required. The role of surgery is still undefined. Open ligation, banding, or closure of the arteriovenous malformation feeding artery have been proposed but rejected, as they are followed by an unacceptably high incidence of complications, derived from ischemia of the biliary tree. Orthotopic liver transplantation (OLT) has been successfully attempted in 28 patients with cardiac, biliary, or portal hypertension as well as mixed clinical presentations. Twenty-four were alive at time of data collection. Cardiovascular and pulmonary functions have improved after the operation in most cases. Intrahepatic relapse of the hallmark lesion of the disease (telangiectasia and arterovenous malformation) has been recently described in two cases. OLT represents a valuable therapeutic option for hepatic-based HHT, provided early diagnosis and referral to a specialized unit.

A systematic review of two different trimetoprim-sulfamethoxazole regimens used to prevent Pneumocystis jirovecii and no prophylaxis at all in transplant recipients: appraising the evidence.

BACKGROUND: The aim of this study was to clarify the potential advantages of a low-dose regimen of trimethoprim-sulfamethoxazole prophylaxis to prevent Pneumocystis jirovecii pneumonia (PJP) in transplant recipients (80/400 mg/d every day or 160/800 mg/d every other day) with those obtained from the full-dose prophylaxis (160/800 mg/d every day) or no prophylaxis. METHODS: Prospectively randomized and retrospectively case controlled studies were selected. RESULTS: Four studies matched the inclusion criteria-2 randomized and 2 case controls-for a total of 570 patients. The pneumonia incidence was 0% after full-dose prophylaxis (0/181), 1% after the low-dose regimen (1/105), and 11% with no prophylaxis (31/284). Pneumonia occurrences were significant lower between the full-dose prophylaxis versus the no prophylaxis group (0% vs 11%; P < .001), and between the low-dose and no prophylaxis groups (1% vs 11%; P < .001). There was no difference between patients receiving the full-dose prophylaxis versus the low-dose regimen (0% vs 1%; P = NS). CONCLUSIONS: The low-dose gives similar results as the full-dose regimen for the prevention of PJP and seems a feasible, safe option for transplanted patients.

Clinical operational tolerance after solid organ transplantation.

Clinical operational tolerance (COT) is a clinical condition obtainable with difficulty after solid organ transplantation (SOT). It is characterized by perfectly normal graft function in the total absence of maintenance immunosuppression. Major benefits deriving from the onset of COT are the reduction of risk for immunosuppression-related side effects and the improved quality of life. Currently, COT can be safely achieved in stable liver transplant recipients; it remains a challenge after renal transplantation. Only 1 case of COT has been reported after lung transplantation; no cases have been described after other types of SOT. Overall, mechanisms of COT are unclear and strategies to induce COT cannot be applied on a regular base to a large cohort of SOT recipients. Due to the failure of molecularly based tolerogenic protocols, great hope relies in the adoption of cell-based strategies.