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Objectives: To describe a cohort of Wilson disease (WD) pediatric cases, and to point out the diagnostic particularities of this age group and the long-term outcome., Methods: Clinical data of 182 pediatric patients included in the French WD national registry from 01/03/1995 to 01/06/2019 were gathered., Results: Diagnosis of WD was made at a mean age of 10.7 ± 4.2 years (range 1-18 years). At diagnosis, 154 patients (84.6%) had hepatic manifestations, 19 (10.4%) had neurological manifestations, and 9 patients (4.9%) were asymptomatic. The p.His1069Gln mutation was the most frequently encountered (14% of patients).Neurological patients were diagnosed at least 1 year after they presented their first symptoms. At diagnosis, the median urinary copper excretion (UCE) was 4.2 μmol/24 hours (0.2-253). The first-line treatment was d-penicillamine (DP) for 131 (72%) patients, zinc salts for 24 (13%) patients, and Trientine for 17 (9%) patients. Liver transplantation was performed in 39 (21.4%) patients, for hepatic indications in 33 of 39 patients or for neurological deterioration in 6 of 39 patients, mean Unified Wilson's Disease Rating Scale of the latter went from 90 ± 23.1 before liver transplantation (LT) to 26.8 ± 14.1 (P < 0.01) after a mean follow-up of 4.3 ± 2.5 years. Overall survival rate at 20 years of follow-up was 98%, patient and transplant-free combined survival was 84% at 20 years., Conclusion: Diagnosis of WD can be challenging in children, particularly at the early stages of liver disease and in case of neurological presentation; hence the support of clinical scores and genetic testing is essential. Diagnosis at early stages and proper treatment ensure excellent outcomes, subject to good long-term treatment compliance. LT is a valid option for end-stage liver disease not responding to treatment and can be discussed for selected cases of neurological deterioration., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: To evaluate the effect of liver transplantation (LT) in patients with Wilson disease (WD) with severe neurologic worsening resistant to active chelation., Methods: French patients with WD who underwent LT for pure neurologic indication were retrospectively studied. Before LT and at the last follow-up, neurologic impairment was evaluated with the Unified Wilson's Disease Rating Scale (UWDRS) score, disability with the modified Rankin Scale (mRS) score, and hepatic function with the Model for End-stage Liver Disease score, together with the presence of a Kayser-Fleischer ring (KFR), brain MRI scores, and copper balance. The survival rate and disability at the last follow-up were the coprimary outcomes; evolution of KFR and brain MRI were the secondary outcomes. Prognosis factors were further assessed., Results: Eighteen patients had LT. All were highly dependent before LT (median mRS score 5). Neurologic symptoms were severe (median UWDRS score 105), dominated by dystonia and parkinsonism. The cumulated survival rate was 88.8% at 1 year and 72.2% at 3 and 5 years. At the last follow-up, 14 patients were alive. Their mRS and UWDRS scores improved ( p < 0.0001 and p = 0.0003). Eight patients had a major improvement (78% decrease of the UWDRS score), 4 a moderate one (41% decrease), and 2 a stable status. KFR and brain MRI scores improved ( p = 0.0007). Severe sepsis ( p = 0.011) and intensive care unit admission ( p = 0.001) before LT were significantly associated with death., Conclusions: LT is a rescue therapeutic option that should be carefully discussed in selected patients with neurologic WD resistant to anticopper therapies (chelators or zinc salts) as it might allow patients to gain physical independency with a reasonable risk., Classification of Evidence: This study provides Class IV evidence that for patients with WD with severe neurologic worsening resistant to active pharmacologic therapy, LT might decrease neurologic impairment., (© 2020 American Academy of Neurology.)

Background: Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension associated with portal hypertension. Its presence is a major stake for cirrhotic patients requiring liver transplantation (LT), with increased postoperative mortality and unpredictable evolution after transplantation. The aim was to study outcomes after liver transplantation in patients with portopulmonary hypertension and to identify factors associated with normalization of pulmonary hypertension., Methods: Patients with portopulmonary hypertension who underwent LT between 2008 and 2016 in 8 French centers were retrospectively included. Pulmonary artery pressure was established by right heart catheterization before and after LT. Primary endpoint was the normalization of pulmonary artery pressure after LT., Results: Twenty-three patients who received liver transplant between 2008 and 2016 were included. Two (8.7%) patients died in the immediate posttransplant period from right heart failure. With appropriate vasoactive medical treatment and LT, pulmonary arterial pressure was normalized in 14 patients (60.8%), demonstrating recovery from portopulmonary hypertension. In univariate analysis, the use of vasoactive combination therapy was the only prognostic factor for pulmonary arterial hypertension normalization after LT., Conclusions: Treatment of portopulmonary hypertension with a combination of vasoactive drugs allows LT with acceptable postoperative cardiovascular-related mortality and normalization of pulmonary hypertension in the majority of the patients.

Cognitive impairment in adult patients experiencing Wilson disease is now more clearly described, even in liver forms of the disease. Although this condition can appear during childhood, the cognitive abilities of children have not yet been reported in a substantial case series. This retrospective study included 21 children with Wilson disease who had undergone general cognitive assessment. The results argue in favor of a poor working memory capacity in the liver form of the disease, and more extensive cognitive impairments in its neurological form. Extensive neuropsychological investigations on all children experiencing Wilson disease are thus required.

Background: Calcineurin inhibitor-induced renal dysfunction is a major problem in liver transplantation. Interleukin-2 receptor antagonist induction followed by delayed tacrolimus (Tac) administration may minimize the renal insult without compromising immunoprotection., Methods: This open, randomized, multicenter trial evaluated the benefit of daclizumab induction with delayed Tac on renal function at 6 months; an observational study was continued for 18 months. Liver transplant patients with a 12-hr serum creatinine (SrC) level less than 180 micromol/L received either delayed Tac with daclizumab induction (n=98) or standard Tac (n=101) both combined with mycophenolate mofetil and steroids. The primary endpoint was the incidence of SrC level more than 130 micrommol/L at 6 months., Results: The incidence was 22.4% with delayed Tac and 29.7% with standard Tac (P=ns), which remained unchanged at 12 months (21.6% and 23.9%) but increasing slightly at 24 months (29.0% and 32.9%), respectively. A post hoc analysis of renal function was done based on patients stratification by SrC at 12 hr (100 micromol/L) showing no difference in SrC values at 6 months regardless of the 12-hr values despite a trend toward better estimated glomerular filtration rate for patients with 12-hr value less than 100 micromol/L in the delayed Tac group. Biopsy-proven acute rejection was similar at 6 months (17.5% and 18.75%), 12 months (23.5% and 23.8%), and 24 months (24.5% and 25.7%), respectively. Patient and graft survival in both groups were comparable and good. Similar types and incidences of adverse events were reported in both groups at all time., Conclusions: Delay of Tac does not benefit renal function in liver transplant recipients with a good renal function at baseline.

Background: Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication of organ transplantation that leads to death in more than 50% of cases. The aim of this work was to identify specific risk factors for lymphoproliferative disorders after liver transplantation in adults., Methods: A total of 480 consecutive patients who underwent transplantation between 1986 and 1997 were studied (323 men, 157 women; mean age: 49.8+/-10.4 years). Demographics, the indication for transplantation, the immunosuppressive regimens, the incidence of rejection episodes, and Epstein-Barr virus infection were analyzed. Univariate and multivariate analysis were used to identify factors predictive of PTLD., Results: Sixteen cases of PTLD (3.3%) occurred at a median of 5.5 (range, 1-39) months after liver transplantation. All 16 cases occurred in patients with evidence of exposure to Epstein-Barr virus before transplantation. In multivariate analysis, the use of antilymphocyte antibodies (P=0.007, relative risk [RR]=4.2, 95% confidence interval [CI]=1.5-11.7), age older than 50 years (P=0.037, RR=3.5, 95% CI=0.95-13.0), liver transplantation for hepatitis C virus cirrhosis (P=0.015, RR=8.7, 95% CI=1-78.3), and liver transplantation for alcoholic cirrhosis (P=0.015, RR=9.6, 95% CI=1.2-77.2) were independently associated with the onset of PTLD., Conclusion: Liver transplantation for hepatitis C virus-related and alcoholic cirrhosis and age older than 50 years are three additional risk factors for lymphoproliferative disorder independent of the use of antilymphocyte antibodies. The use of antilymphocyte antibodies after liver transplantation should be avoided in these categories of patients, especially those older than 50 years.