To estimate protection from cytomegalovirus (CMV) replication after solid organ transplantation, CMV serology has been considered insufficient and thus CMV immunity is increasingly assessed by cellular in vitro methods. We compared two commercially available IFN-γ ELISpot assays (T-Track CMV and T-SPOT.CMV) and an IFN-γ ELISA (QuantiFERON-CMV). Currently, there is no study comparing these three assays. The assays were performed in 56 liver transplant recipients at the end of antiviral prophylaxis and one month thereafter. In CMV high- or intermediate-risk patients the two ELISpot assays showed significant correlation (p < 0.0001, r > 0.6) but the correlation of the ELISpot assays with QuantiFERON-CMV was weaker. Results of both ELISpot assays were similarly predictive of protection from CMV-DNAemia ≥500 copies/mL [CMV pp65 T-SPOT.CMV at the end of prophylaxis: area under curve (AUC) = 0.744, cut-off 142 spot forming units (SFU), sensitivity set to 100%, specificity 46%; CMV IE-1 T-Track CMV at month 1: AUC = 0.762, cut-off 3.5 SFU, sensitivity set to 100%, specificity 59%]. The QuantiFERON-CMV assay was inferior, reaching a specificity of 23% when setting the sensitivity to 100%. In conclusion, both CMV-specific ELISpot assays appear suitable to assess protection from CMV infection/reactivation in liver transplant recipients.

Background: Tenofovir disoproxil fumarate (TDF) is frequently used for treatment of and prophylaxis against reactivation of hepatitis B virus (HBV) after liver transplant (LT). Because TDF can lead to renal impairment and a decrease in bone mineral density (BMD), the prodrug tenofovir alafenamide (TAF) may be considered a viable alternative with fewer adverse effects. Only limited information is available about the use of TAF for LT recipients. We report a European single-center experience with TAF as treatment for LT patients.Methods: This retrospective analysis involved 29 LT recipients receiving standard immunosuppressants (mainly calcineurin inhibitors). Demographic and clinical data were documented at baseline upon switch to TAF and at various time points thereafter.Results: None of the patients experienced HBV reactivation after the switch to TAF.Liver and renal function remained stable. Drug levels of immunosuppressive agents did not change significantly after the switch. After 1 year, 22 patients were still taking TAF; two patients had been lost to follow-up; one patient had died; and four patients had discontinued therapy because of TAF-related adverse effects. No serious adverse effects were reported. Conclusions:Tenofovir alafenamide exhibits high antiviral efficacy and a good safety profile for LT recipients. Still, the safety and tolerability of TAF for organ transplant patients should be evaluated in larger cohorts.

In conclusion, substantial dose reduction and daily administration of low doses of TAC compose a safe and efficient immunosuppressive regimen during TVR-based triple therapy.

Background: Recurrent hepatitis C infection after liver transplantation (LT) is associated with lower rates of graft and patient survival. Methods: Here we describe the first use of daclatasvir, simeprevir, and ribavirin (RBV) as an all-oral triple regimen administered to 6 liver transplant recipients with recurrent hepatitis C, one with GT 1a and 5 with GT 1b. All patients were treated for 24 weeks. Trough levels of immunosuppression, laboratory measures, and potential adverse effects were closely monitored. Results: For all patients, viral load became undetectable between treatment weeks 4 and 12. One patient experienced a viral breakthrough at the 10th week of treatment; this was associated with the selection of resistance-associated variants (D168Y in NS3 and ΔP32 in NS5A). For the other 5 patients, end-of-treatment response and for 4 patients SVR24 was achieved. Viremia recurred in one patient 4 weeks after the end of treatment, which was again associated with the selection of resistance-associated variants (D168V in NS3 and ΔP32 in NS5A). Clinical measures of liver function improved substantially for all patients. Adverse events were few and limited to moderate anemia caused by RBV. Importantly, adjustments to the immunosuppressant dosage were not required. Conclusions: The described regimen appears to be safe and effective for liver transplant patients and will be a promising treatment regimen for post-LT patients.

Everolimus (EVR) is a mammalian target of rapamycin (mTOR) inhibitor commonly used for immunosuppression (IS) after liver transplantation (LT). However, there are concerns about whether mTOR inhibitors may move the hemostatic balance toward a higher likelihood of thrombosis. The present study aimed to investigate potential coagulation disorders after the administration of EVR. We evaluated 54 patients after conversion to an EVR‐based IS regimen (n = 26) and compared those patients with patients who were switched to extended‐release tacrolimus (TAC) but had never received EVR (n = 28). At baseline and again at 1 month and 6 months after conversion, we measured international normalized ratio, activated partial thromboplastin time, and anticoagulation and fibrinolysis factors, and we performed rotational thromboelastometry (ROTEM). Data were analyzed with a Mann‐Whitney U test, a repeated‐measure analysis of variance, and a Fisher’s exact test. Statistical significance was set at the level of P ≤ 0.05. Plasma levels of von Willebrand factor, fibrinogen, and factor VIII were significantly higher than baseline levels at 1 month and 6 months after conversion of IS to EVR (P < 0.001); plasma levels of protein C, protein S, and plasminogen also increased significantly (P < 0.001). ROTEM confirmed a significant increase in maximum clot firmness in EXTEM, INTEM, and FIBTEM assays (P < 0.001). In all assays, maximum lysis was significantly lower than baseline levels at 1 month and 6 months after conversion to EVR. Patients converted to IS with extended‐release TAC exhibited no significant changes in coagulation variables. Retrospective analysis showed a significantly higher incidence of thromboembolic complications among patients treated with EVR‐based IS than among those treated with extended‐release TAC (P < 0.01). In conclusion, the administration of EVR after LT seems to modify hemostasis to a procoagulant state. Thrombophilia screening before conversion may determine which patients will benefit from conversion to EVR‐based IS.