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LCP-tacrolimus displays enhanced oral bioavailability compared to immediate-release (IR-) tacrolimus. The ENVARSWITCH study aimed to compare tacrolimus AUC0-24 h in stable kidney (KTR) and liver transplant recipients (LTR) on IR-tacrolimus converted to LCPtacrolimus, in order to re-evaluate the 1:0.7 dose ratio recommended in the context of a switch and the efficiency of the subsequent dose adjustment. Tacrolimus AUC0-24 h was obtained by Bayesian estimation based on three concentrations measured in dried blood spots before (V2), after the switch (V3), and after LCP-tacrolimus dose adjustment intended to reach the pre-switch AUC0-24 h (V4). AUC0-24 h estimates and distributions were compared using the bioequivalence rule for narrow therapeutic range drugs (Westlake 90% CI within 0.90-1.11). Fifty-three KTR and 48 LTR completed the study with no major deviation. AUC0-24 h bioequivalence was met in the entire population and in KTR between V2 and V4 and between V2 and V3. In LTR, the Westlake 90% CI was close to the acceptance limits between V2 and V4 (90% CI = [0.96-1.14]) and between V2 and V3 (90% CI = [0.96-1.15]). The 1:0.7 dose ratio is convenient for KTR but may be adjusted individually for LTR. The combination of DBS and Bayesian estimation for tacrolimus dose adjustment may help with reaching appropriate exposure to tacrolimus rapidly after a switch. [ABSTRACT FROM AUTHOR]

Summary: There are scarce data on the impact of COVID‐19 pandemic on liver transplantation (LT) in Europe. The aim of this study was to obtain a preliminary data on incidence, management, and outcome of COVID‐19 in liver transplant recipients and candidates in Europe. An Internet‐based survey was sent to the centers affiliated with European Liver Transplant Registry (ELTR). One hundred nine out of 149 (73%) of ELTR centers located in 28 European countries (93%) responded. Ninety‐four (86%) of the centers tested all donors, and 75 (69%) centers tested all LT recipients for SARS‐CoV‐2. Seventy‐three (67%) centers selected recipients for LT in the COVID‐19 pandemic, whereas 33% did not. Eighty‐eight centers reported COVID‐19 infection in 57 LT candidates and in 272 LT recipients. Overall crude incidence of COVID‐19 among LT candidates and recipients was estimated 1.05% (range 0.5–20%) and 0.34% (range 0.1–4.8%), respectively, and it was significantly higher among candidates (P < 0.001). Crude rate of death was 18% (10/57) among candidates and 15% (36/244) among recipients. This first large‐scale European snapshot study clearly shows that both LT candidates and recipients are at a high risk for COVID‐19. These results plead for an early and pro‐active screening of COVID‐19 symptoms in these populations. [ABSTRACT FROM AUTHOR]

Summary: The liver is frequently affected in patients with sickle cell disease (SCD), but few reports have described liver transplantation (LT) in patients with SCD. We present a thorough analysis of the largest single‐center series of LT in patients with SCD and the first systematic review. There were 21 patients with a median age of 37.6 years. LT was performed for acute liver failure related to the sickling process (57%) or electively for end‐stage liver disease (43%). Prior to LT, 13 patients (62%) were in the intensive care unit and required mechanical ventilation (33%), vasopressor therapy (24%), renal replacement therapy (10%), or molecular adsorbent recirculating system therapy (19%). Post‐LT morbidity and mortality were 95% and 33%, respectively. Patient survival at 1 and 5 years were 58.3% and 41.7%, respectively, in the urgent group and 88.9% and 77.8%, respectively, in the elective group. A total of 22 transplant patients with SCD are described in 20 articles in the literature. The 1‐ and 5‐year patient survival rates for the 18 evaluable patients were 75% and 65%, respectively. LT improves survival in patients with SCD and acute liver failure or end‐stage liver disease but is associated with high morbidity during the early postoperative course. [ABSTRACT FROM AUTHOR]

Summary: Factors affecting outcomes in liver transplant (LTx) recipients with hepatocellular carcinoma (HCC) and hepatitis C viral (HCV) infection include the choice of immunosuppression. Here, we analyzed the HCV+ subgroup of patients from the randomized controlled, international SiLVER Study. We performed a post hoc analysis of 166 HCV+ SiLVER Study patients regarding HCC outcome after LTx. Control patients (group A: n = 88) received mTOR inhibitor (mTORi)‐free, calcineurin inhibitor (CNI)‐based versus sirolimus‐based immunosuppression (group B: n = 78). We found no significant difference regarding HCV‐RNA titers between group A and B. Since no effect in group B could be due to variable sirolimus dosing, we split group B into patients receiving sirolimus‐based immunosuppression + CNIs for >50% (B1; n = 44) or <50% (B2; n = 34) of the time. While there remained no difference in HCV‐RNA titer between groups, HCC recurrence‐free survival in group B1 (81.8%) was markedly better versus both group A (62.7%; P = 0.0136) and group B2 (64.7%; P = 0.0326); Interestingly, further subgroup analysis revealed an increase (P = 0.0012) in liver enzyme values in group B2. Taken together, in HCV‐infected patients with HCC and LTx, mTORi immunosuppression + CNIs yields excellent outcomes. Unexpectedly, higher levels of liver inflammation and poorer outcomes occur with mTORi monotherapy in the HCV+ subgroup. [ABSTRACT FROM AUTHOR]

Summary: Concerns related to equity and efficacy of our previous center‐based allocation system have led us to introduce a patient‐based allocation system called the "Liver Score" that incorporates the model for end‐stage liver disease (MELD) score. The main objective of this study was to compare waitlist and post‐transplant survivals before and after implementation of the "Liver Score" using the French transplant registry (period before: 2004–2006 and period after: 2007–2012). Patients transplanted during the second period were sicker and had a higher MELD. One‐year waitlist survival (74% vs. 76%; P = 0.8) and 1‐year post‐transplant survival (86.3% vs. 85.7%; P = 0.5) were similar between the 2 periods. Cirrhotic recipients with MELD>35 had lower 1‐year post‐transplant survival compared to those with MELD <35 (74.8% vs. 86.3%; P < 0.01), mainly explained by their higher intubation and renal failure rates. The MELD showed a poor discriminative capacity. In cirrhotic recipients with MELD>35, patients presenting 2 or 3 risk factors (dialysis, intubation, or infection) had a lower 1‐year survival compared to those with none of these risk factors (61.2% vs. 92%; P < 0.01). The implementation of the MELD‐based allocation system has led to transplant sicker patients with no impact on waitlist and post‐transplant survivals. Nevertheless, selection of patients with MELD>35 should be completed to allow safe transplantation. [ABSTRACT FROM AUTHOR]

Summary: Locoregional treatment while on the waiting list for liver transplantation (Ltx) for hepatocellular carcinoma (HCC) has been shown to improve survival. However, the effect of treatment type has not been investigated. We investigate the effect of locoregional treatment type on survival after Ltx for HCC. We investigated patients registered in the European Liver Transplant Registry database using multivariate Cox regression survival analysis. Information on locoregional therapy was registered for 4978 of 23 124 patients and was associated with improved overall survival [hazard ratio (HR) 0.84 (0.73–0.96)] and HCC‐specific survival [HR 0.76 (0.59–0.98)]. Radiofrequency ablation (RFA) was the one monotherapy associated with improved overall survival [HR 0.51 (0.40–0.65)]. In addition, the combination of RFA and transarterial chemoembolization also improved survival [HR 0.74 (0.55–0.99)]. Adjusting for factors related to prognosis, disease severity, and tumor aggressiveness, RFA was highly beneficial for overall and HCC‐specific survival. The effect may represent a selection of patients with favorable tumor biology; however, the treatment may be effective per se by halting tumor progression. Clinicaltrials.gov number: NCT02995096. [ABSTRACT FROM AUTHOR]

Recurrence of hepatitis C virus infection following liver transplantation ( LT) for hepatitis C is universal. After LT, hepatitis C is associated with accelerated fibrosis progression and reduced graft and patient survival. Furthermore, responses to antiviral therapy in patients with recurrent hepatitis C virus post-transplant are consistently sub-optimal. Calcineurin inhibitors ( CNIs) like cyclosporine A (CsA) and tacrolimus continue to dominate immunosuppressive regimens in this population; however, there is still uncertainty as to whether either offers an advantage in terms of patient outcomes. Although tacrolimus demonstrates improved efficacy in the general LT population, differences have begun to emerge between these agents regarding diabetogenic potential, antiviral activity, and fibrosis progression in patients with hepatitis C. This review critically evaluates the existing literature, providing an overview of the reported differences, concluding that despite conflicting evidence, a potential benefit of CsA in patients with hepatitis C is supported by the data and warrants further investigation. Future studies examining the role of CNIs in hepatitis C virus-positive LT recipients are required to accurately examine the effects of CNIs on outcomes such as fibrosis progression, survival, and effects on response to antiviral therapy, to provide robust information that allows clinicians to make an informed choice concerning which CNI is best for their patients. [ABSTRACT FROM AUTHOR]

We read with great interest the letter by Rodriguez-Peralvarez et al. where the authors discuss the incidence of COVID-19 in liver transplant (LT) recipients in Europe and comment on the results of the recently published early survey of European Liver and Intestine Transplantation Association (ELITA) and European Liver Transplant Registry (ELTR) [1,2]. However, in contrast to the national studies, the strength of our ELITA-ELTR study is a better description of the incidence of COVID-19 in LT recipients at the European level at the beginning of the pandemic. At the same time, studies conducted in centres with a high incidence of COVID-19 have reported that negative RT-PCR test, but with positive CT features, should be highly suggestive for COVID-19 [4-6]. [Extracted from the article]