Comorbid psychiatric disorders and long-term survival after liver transplantation in transplant facilities with a psychiatric consultation-liaison team: a multicenter retrospective study.

OBJECTIVE: Comorbid psychiatric disorders negatively affect the survival rate of patients with some physical disorders. In liver transplant recipients, various psychiatric disorders have been identified as worsening prognosis. However, little is known about how the presence of any comorbid (overall) disorders affect the survival rate of transplant recipients. In this study, we examined the effect of overall comorbid psychiatric disorders on survival rate in liver transplant recipients. METHODS: A total of 1006 recipients who underwent liver transplantation between September 1997 and July 2017 across eight transplant facilities with a psychiatric consultation-liaison team were identified consecutively. Recipients were categorized into those with comorbid psychiatric disorders and those without comorbid psychiatric disorders. In the comorbid psychiatric disorder group, psychiatric disorder diagnosis and time of diagnosis were investigated retrospectively. RESULTS: Of the 1006 recipients, 294 (29.2%) had comorbid psychiatric disorders. Comorbid psychiatric disorders in the 1006 recipients were insomnia (N = 107, 10.6%), delirium (N = 103, 10.2%), major depressive disorder (N = 41, 4.1%), adjustment disorder (N = 19, 1.9%), anxiety disorder (N = 17, 1.7%), intellectual disability (N = 11, 1.1%), autism spectrum disorder (N = 7, 0.7%), somatic symptom disorder (N = 4, 0.4%) schizophrenia (N = 4, 0.4%), substance use disorder (N = 24, 2.4%) and personality disorder (N = 2, 0.2%). The most common time of psychiatric disorder diagnosis was within the first 3 months after liver transplantation (51.6%). The final mortality in patients with comorbid psychiatric disorder diagnosis during the five periods (pretransplant, transplant to 3 months, months to 1 year, 1 to 3 years, and over 3 years posttransplant) was 16.2%, 18.8%, 39.1%, 28.6%, and 16.2% respectively, and there were no significant differences between the five periods (χ2 = 8.05, df = 4, p = 0.09). Overall comorbid psychiatric disorders were significantly associated with shorter survival time (log-rank test: p = 0.01, hazard ratio: 1.59 [95% confidence interval: 1.14-2.21], survival rate at the endpoint [%]: 62.0 vs. 83.3). However, after adjusting for confounding variables using Cox proportional hazards regression, there was no significant effect of overall comorbid psychiatric disorders on prognosis. CONCLUSION: Comorbid psychiatric disorders did not affect the survival rate of liver transplant recipients in this study.

Low seroprevalence of SARS-CoV-2 antibodies in a liver transplant cohort.

Solid organ transplant recipients might be at greater risk for acquisition and mortality because of SARS-CoV-2. There are no data regarding SARS-CoV-2 seroprevalence among liver transplant (LT) recipients, and whether it is different from that of the general population or other immunosuppressed groups. We evaluated the prevalence of IgG SARS-CoV-2 antibodies among LT recipients to estimate the frequency of asymptomatic SARS-CoV-2 infection using serological assays in our outpatient clinic. We conducted a cross-sectional analysis from 10 May to 26 October 2020 of all adult (>18 years) LT recipients that underwent a routine laboratory test for the outpatient clinic follow-up at the Hospital Universitari Vall d'Hebron (Barcelona) in which we included serological testing for SARS-CoV-2. Nine out of 294 LT recipients (3.1%) tested positive for anti-SARS-CoV-2 IgG antibodies. Five of them (55.5%) had suffered clinically symptomatic SARS-CoV-2 infection confirmed by RT-PCR, four (44.4%) had presented compatible symptoms but without microbiological confirmation and only one patient (1/9, 11.1%) tested positive without any previous symptom. SARS-CoV-2 seroprevalence among LT recipients in an area highly affected by the pandemic is lower than in the general population in the same area. These results render the possibility of asymptomatic infection in LT recipients very unlikely.

Effectiveness of tigecycline in the treatment of infections caused by carbapenem-resistant gram-negative bacteria in pediatric liver transplant recipients: A retrospective study.

INTRODUCTION: Tigecycline (TGC) is effective for the infections caused by carbapenem-resistant gram-negative bacteria (CRGNB) in adults, but it is not investigated systematically in children because of concern about adverse effects. This study aimed to analyze the effectiveness of TGC in treating CRGNB infections in children after receiving liver transplant. METHODS: The subjects in this retrospective study were pediatric liver transplant recipients treated with TGC for at least 3 days to fight microbiologically verified CRGNB infection after initial antibiotic failure during the period from January 2014 to May 2018. Clinical and microbiological outcomes were reviewed to evaluate the efficacy and safety of TGC. RESULTS: Of the 1177 pediatric liver transplant recipients, 13 patients were eligible for inclusion in this analysis. All the patients received TGC at dose of 2 mg/kg every 12 hours for a duration of 10.1 ± 5.1 days on average to treat CRGNB infections, including complicated intra-abdominal infection, ventilator-associated pneumonia, and bloodstream infection. The isolates included Klebsiella pneumoniae (69.2%, 9/13) and Acinetobacter baumannii (30.8%, 4/13). Clinical efficacy was achieved in 84.6% (11/13) and pathogen eradicated in 69.2% (9/13) of the patients. The overall mortality rate was 15.4% (2/13). No TGC-related serious adverse event was reported. CONCLUSION: Tigecycline can be considered in combination antimicrobial regimen for treating CRGNB-related infections in pediatric liver transplant recipients.

Current Knowledge on Skin Cancer Prevention in Liver Transplant Recipients.

The improved survival of liver transplant recipients (LTRs) has been accompanied by a concomitant rise in long-term liver transplantation complications, including skin cancer. A recent study found that the prevalence of skin cancer among LTRs is 13.5%, a rate equivalent to that observed among kidney transplant recipients. Given the morbidity associated with skin cancer in LTRs, an individualized, multidisciplinary approach to skin cancer prevention that incorporates patient education, encourages consistent use of primary prevention methods, and ensures routine dermatologic screening should be universally adopted in this population. Chemopreventative measures should be considered in LTRs with a high skin cancer burden. Furthermore, additional studies should be performed in order to systematize these recommendations.

A Quality Control Study of the Adherence to Recommended Physiological Targets for the Management of Brain-Dead Organ Donors in South Australian Intensive Care Units.

BACKGROUND: The Australian and New Zealand Intensive Care Society and the Australasian Transplant Coordinators Association provide recommendations on the physiological management of brain-dead donors. PROBLEM STATEMENT: How often physiological targets are prescribed for brain-dead donors in Australian intensive care units (ICUs), and how well these compare to recommended targets is unknown. It is also unknown how often recommended targets are achieved, irrespective of prescribed targets. METHODS: We performed a retrospective, observational quality control study in 81 adult (>18 years) brain-dead donors to describe how often physiological targets were prescribed, comparing these to current guidelines. We determined the proportion of observations within the recommended target range, irrespective of any prescribed target. We aimed to identify poor adherence to recommended targets to guide future quality improvement initiatives. OUTCOMES: Seventy-four (91%) donors had at least 1 prescribed physiological target written on the ICU chart, with a median of 2 (range 2-5), and a maximum of 13 targets. Prescribed targets appeared to adhere well with recommended targets. Most recommended physiological targets were met irrespective of any prescribed target. However, one-quarter of serum sodium observations and one-third of blood glucose levels were above the recommended target. IMPLICATIONS FOR PRACTICE: Quality improvement initiatives are required to improve the prescription of physiological targets in brain-dead donors in South Australia. Serum sodium and serum glucose targets were not met. However, this most likely reflects the need for current guidelines to be updated in line with current evidence.

Low to Intermediate Dose Atropine Administration During Dobutamine Stress Echocardiography in the Pre-Liver Transplant Population.

INTRODUCTION: Dobutamine stress echocardiography (DSE) is frequently used to screen for obstructive coronary artery disease in the pre-liver transplant evaluation. Although atropine is a commonly used adjunctive medication, no study has evaluated its side effect profile in patients with end-stage liver disease (ESLD). RESEARCH QUESTION: What is the safety of atropine in candidates undergoing pre-liver transplant evaluation when atropine is used in stress testing? DESIGN: This multicenter, prospective study enrolled patients over a 6-month period undergoing pre-liver transplant evaluation. Each patient completed a questionnaire assessing anticholinergic-related symptoms within 24 hours of testing and 48 hours following. Comparisons were made among patients receiving any atropine dose versus those who did not and among patients receiving at least 1 mg atropine and those receiving less/none. RESULTS: Forty patients were evaluated, and 32 (80%) had adjunctive atropine administered. No differences in clinical characteristics were noted. In comparisons among patients receiving any dose of atropine with those who did not, questionnaire results indicated a higher rate of nausea prior to testing and higher overall symptom severity following testing in patients not receiving atropine. In comparisons among patients receiving less than 1 mg atropine with those receiving at least 1 mg atropine, no difference in pre- or posttesting questionnaire responses was present. No patient in the study required reversal agents or hospitalization within 7 days of testing. CONCLUSIONS: Atropine, a hepatically metabolized medication, did not predispose patients with ESLD to an increased symptom burden, and clinical outcomes related to DSE were unaffected.

Patients From Appalachia Have Reduced Access to Liver Transplantation After Wait-Listing.

BACKGROUND: The Appalachian region is medically underserved and characterized by high morbidity and mortality. We investigated disparities among patients listed for liver transplantation (LT) in wait-list outcomes, according to residence in the Appalachian region. METHODS: Data on adult patients listed for LT were obtained from the United Network for Organ Sharing for July 2013 to December 2015. Wait-list outcomes were compared using cause-specific hazard models by region of residence (Appalachian vs non-Appalachian) among patients listed at centers serving Appalachia. Posttransplant patient and graft survival were also compared. The study included 1835 LT candidates from Appalachia and 5200 from non-Appalachian regions, of whom 1016 patients experienced wait-list mortality or were delisted; 3505 received liver transplants. RESULTS: In multivariable analyses, patients from Appalachia were less likely to receive LT (hazard ratio [HR] = 0.86; 95% confidence interval [CI]: 0.79-0.93; P < .001), but Appalachian residence was not associated with wait-list mortality or delisting (HR = 1.03; 95% CI: 0.89-1.18; P = .696). Among liver transplant recipients, patient and graft survival did not differ by Appalachian versus non-Appalachian residence. CONCLUSION: Appalachian residence was associated with lower access to transplantation after listing for LT. This geographic disparity should be addressed in the current debate over reforming donor liver allocation and patient priority for LT.

ELITA consensus statements on the use of DAAs in liver transplant candidates and recipients.

The advent of safe and highly effective direct-acting antiviral agents (DAAs) has had huge implications for the hepatitis C virus (HCV) transplant field, and changed our management of both patients on the waiting list and those with HCV graft re-infection after liver transplantation (LT). When treating HCV infection before LT, HCV re-infection of the graft can be prevented in nearly all patients. In addition, some candidates show a remarkable clinical improvement and may be delisted. Alternatively, HCV infection can be treated post-LT either soon after the transplant, taking advantage of the removal of the infected native liver, or at the time of disease recurrence, as was carried out in the past. In either case, some DAAs have a limited use because of their drug to drug interactions with various immunosuppressants as well as the many other drugs liver transplant recipients are often prescribed. In addition, some DAAs should be avoided in case of severe renal failure, which is not an unusual complication after LT. The present document provides a series of consensus statements on the LT issues that have not been extensively addressed previously. These statements have been developed to support physicians and other stakeholders in charge of LT candidates and recipients when deciding to treat HCV, especially in difficult situations.

Abdominal emergencies after liver transplantation: Presentation and surgical management.

With an increasing number of liver transplantation (LT) and an enhanced overall survival, LT recipients are more likely to be admitted in emergency departments of general hospitals. Yet, in LT recipients, common but also benign symptoms may reveal a LT-related (or not) severe condition. To improve management of LT recipients by emergency physicians and general surgeons and potentially improve long-term outcomes, a clinical review was performed. Overall, CT scan and blood tests should be systematically performed. Immunosuppressive side effects should be excluded using blood tests. LT-related complications are more likely to occur during the first three months after LT, including mainly bile leak, arterial aneurysm, and pseudoaneurysm. Patients should be referred in emergency to tertiary centers. Non-LT-related complications and common abdominal conditions may also be diagnosed in LT recipients. Except in case of diffuse peritonitis or in hemodynamically unstable patients when surgical procedure should be performed, most conditions should be reassessed regarding the immunosuppressive treatment and the adhesive abdominal cavity.

Predictors of Liver Transplant Patient Survival.

OBJECTIVE: Liver transplantation is a costly and risky procedure, representing 25 050 procedures worldwide in 2013, with 6729 procedures performed in the United States in 2014. Considering the scarcity of organs and uncertainty regarding prognosis, limited studies address the variety of risk factors before transplantation that might contribute to predicting patient's survival and therefore developing better models that address a holistic view of transplant patients. This critical review aimed to identify predictors of liver transplant patient survival included in large-scale studies and assess the gap in risk factors from a holistic approach using the Wellbeing Model and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. DATA SOURCE: Search of the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medline, and PubMed from the 1980s to July 2014. STUDY SELECTION: Original longitudinal large-scale studies, of 500 or more subjects, published in English, Spanish, or Portuguese, which described predictors of patient survival after deceased donor liver transplantation. DATA EXTRACTION: Predictors were extracted from 26 studies that met the inclusion criteria. DATA SYNTHESIS: Each article was reviewed and predictors were categorized using a holistic framework, the Wellbeing Model (health, community, environment, relationship, purpose, and security dimensions). CONCLUSIONS: The majority (69.7%) of the predictors represented the Wellbeing Model Health dimension. There were no predictors representing the Wellbeing Dimensions for purpose and relationship nor emotional, mental, and spiritual health. This review showed that there is rigorously conducted research of predictors of liver transplant survival; however, the reported significant results were inconsistent across studies, and further research is needed to examine liver transplantation from a whole-person perspective.

Outcomes of Patients With Familial Transthyretin Amyloidosis After Liver Transplantation.

BACKGROUND: Familial transthyretin amyloidosis is a disease caused by misfolded transthyretin aggregates that can impair multiple organ systems. Liver transplantation is the first-line treatment for familial transthyretin amyloidosis. RESEARCH QUESTION: Our objective is to study outcomes and survival among patients with familial transthyretin amyloidosis after transplantation. DESIGN: All patients undergoing orthotopic liver transplant for familial transthyretin amyloidosis at Mayo Clinic between 1997 and 2012 were reviewed. Baseline clinical characteristics, organs transplanted, and posttransplant clinical course were assessed. RESULTS: Of the 40 patients, 7 patients had the V30M mutation and 33 had other mutations. Nineteen patients received liver only, 19 liver and heart, and 2 combined liver, heart, and kidney transplants. The 5-year overall survival was 85% for those receiving multiple organ transplant and 52% for those receiving liver transplant only ( P = .057). There was no difference in overall survival based on mutation (V30M vs other mutations), but survival was confounded by varied disease involvement and organs transplanted. Those who had early death (≤24 months from liver transplant) had a higher incidence of baseline peripheral neuropathy, autonomic neuropathy, lower modified BMI, and higher alkaline phosphatase. DISCUSSION: Outcomes of orthotopic liver transplant in familial transthyretin amyloidosis are variable due to heterogeneity in mutations and patient status at the time of transplant. Familial transthyretin amyloidosis can progress, despite liver transplantation. Patients receiving combined liver, heart/kidney transplant demonstrated improved survival compared to liver transplant alone.

Anxieties and coping methods of liver transplant recipients regarding pregnancy and delivery.

AIM: To clarify the anxieties experienced by liver transplant recipients and their methods of coping during pregnancy and delivery. BACKGROUND: The recent increase in liver transplantation among adults and the growth in the number of paediatric (until reproductive age) liver transplant recipients have caused an increase in the number of pregnancies and deliveries among patients who have undergone liver transplantation. DESIGN: A qualitative descriptive study. METHODS: Fourteen recipients experienced delivery after undergoing liver transplantation. Data were collected through semi-structured interviews from June 2012 - May 2013. The descriptions obtained about the anxieties felt during pregnancy and the methods for coping were analysed using qualitative content analysis. RESULTS: Regarding anxieties during pregnancy, the two core categories, that is, 'influences on the child born to the liver transplant recipient' and 'the liver transplant recipient's body', and seven other categories were extracted. As for methods of coping, seven categories were extracted such as consulting a healthcare professional, family member or a recipient with a similar experience; accepting the necessity of immunosuppressive therapy; staying positive and avoiding negative thoughts; and practising good health habits. CONCLUSIONS: Liver transplant recipients cope with anxieties about the effects of immunosuppressants on the child and worsening of their physical condition by consulting healthcare professionals and family members and by self-management to maintain their physical condition. Nurses should seek to understand the physical and psychosocial status of each recipient after liver transplantation and provide support to facilitate the physical and psychological stability of liver transplant recipients during pregnancy and delivery.

Fraction of exhaled nitric oxide is higher in liver transplant recipients than in controls from the general population: a cohort study.

Background: Fraction of exhaled nitric oxide with an expiratory flow of 50 mL/s (FENO50) is a biomarker of eosinophilic airway inflammation. Liver transplant recipients have an increased risk of pulmonary infections, but little is known about the burden of chronic pulmonary diseases in this group. We aimed to assess the prevalence of elevated FENO50 in liver transplant recipients and compare it to controls from the general population. Methods: FENO50 was measured in 271 liver transplant recipients from The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study and 1,018 age- and sex-matched controls from The Copenhagen General Population Study (CGPS). Elevated FENO50 was defined as ≥25 or ≥50 parts per billion (ppb). The analyses were adjusted for known and suspected confounders. Results: The median age of the liver transplant recipients was 55 years (interquartile range (IQR) 46-64), and 58% were men. The liver transplant recipients had a higher median FENO50 than the controls [16 ppb (IQR 10-26) vs. 13 ppb (IQR 8-18.), p < 0.001]. Furthermore, the liver transplant recipients had a higher prevalence of elevated FENO50 (for FENO50 ≥25 ppb 27% vs. 11%, p < 0.001 and ≥50 ppb 4% vs. 2%, p = 0.02). The results were similar after adjusting for age, sex, smoking status, use of airway medication, and blood eosinophil counts [the adjusted odds ratio (OR) for FENO50 ≥25 ppb was 3.58 (95% CI: 2.50-5.15, p < 0.0001) and the adjusted OR for FENO50 ≥50 ppb was 3.14 (95% CI: 1.37-7.20, p = 0.007)]. Conclusion: The liver transplant recipients had elevated FENO50, implying increased eosinophilic airway inflammation. The clinical impact of this finding needs further investigation.

Impact of single-nucleotide polymorphisms on tacrolimus pharmacokinetics in liver transplant patients after switching to once-daily dosing.

BACKGROUND: The effects of multidrug resistance-1 (MDR1), ABCC2, and P450 oxidoreductase (POR)*28 gene polymorphisms on tacrolimus metabolism following a switch to once-daily dosing have not been elucidated. We investigated the effects of recipient and donor CYP3A5, MDR1, ABCC2, and POR*28 polymorphisms on tacrolimus pharmacokinetics following a switch to once-daily tacrolimus dosing. METHODS: Eighty-seven liver transplant recipients who were switched from twice- to once-daily tacrolimus dosing following living-donor liver transplantation and 81 matched donors were genotyped for CYP3A5, MDR1 (1236C>T, 2677G>T/A, and 3435C>T), ABCC2 (-24C>T, 1249G>A, and 3972C>T), and POR*28. Tacrolimus dose-adjusted trough levels (C0/dose) before and after the switch were determined and calculated based on past medical records. Recipients were divided into two groups, one group constituted of 38 patients with a C0/dose decrease of less than 30% following conversion (group 1) and the other constituted of 49 patients with a C0/dose decrease of ≥ 30% (group 2). RESULTS: CYP3A5 *1/*3 and *3/*3 were more frequent in recipients in group 1 (60.5% vs. 36.8%), while CYP3A5 *1/*1 was more frequent in group 2 (59.2% vs. 32.7%) (p = 0.016). The proportions of donor ABCC2 1249G>A genotypes AA and AG were higher in group 2 than in group 1 (20.4% vs. 5.3%; p = 0.042). CONCLUSION: Recipient CYP3A5 polymorphism and donor ABCC2 1249G>A polymorphism affected tacrolimus pharmacokinetics following the switch to once-daily dosing. Dose adjustment to maintain therapeutic tacrolimus levels following the switch to once-daily dosing should be considered based on polymorphisms in both the recipient and donor.

Immunogenicity profiling and distinct immune response in liver transplant recipients vaccinated with SARS-CoV-2 inactivated vaccines.

SARS-CoV-2 vaccination has been recommended for liver transplant (LT) recipients. However, our understanding of inactivated vaccine stimulation of the immune system in regulating humoral and cellular immunity among LT recipients is inadequate. Forty-six LT recipients who received two-dose inactivated vaccines according to the national vaccination schedule were enrolled. The clinical characteristics, antibody responses, single-cell peripheral immune profiling, and plasma cytokine/chemokine/growth factor levels were recorded. Sixteen (34.78%) LT recipients with positive neutralizing antibody (nAb) were present in the Type 1 group. Fourteen and 16 LT recipients with undetected nAb were present in the Type 2 and Type 3 groups, respectively. Time from transplant and lymphocyte count were different among the three groups. The levels of anti-RBD and anti-S1S2 decreased with decreasing neutralizing inhibition rates. Compared to the Type 2 and Type 3 groups, the Type 1 group had an enhanced innate immune response. The proportions of B, DNT, and CD3+CD19+ cells were increased in the Type 1 group, whereas monocytes and CD4+ T cells were decreased. High CD19, high CD8+CD45RA+ cells, and low effector memory CD4+/naïve CD4+ cells of the T-cell populations were present in the Type 1 group. The Type 1 group had higher concentrations of plasma CXCL10, MIP-1 beta, and TNF-alpha. No severe adverse events were reported in all LT recipients. We identified the immune responses induced by inactivated vaccines among LT recipients and provided insights into the identification of immunotypes associated with the responders.

Life Expectancy After Liver Transplantation for Hepatocellular Carcinoma With Cirrhosis.

BACKGROUND: Hepatocelluar carcinoma, the most common primary liver cancer, has a historically dire prognosis. For hepatic cancer patients with cirrhosis who underwent liver transplantation, we sought to calculate life expectancies both at time of transplant and several years later, stratified by some key variables, and to determine if survival has improved in recent years. METHODS: Data on 13,797 hepatic cancer patients with cirrhosis who underwent liver transplantation in the MELD era (2002-2018) from the US Organ Procurement and Transplantation Network database were analyzed using the Cox proportional hazards regression model and life table methods. RESULTS: The major factors related to survival were age, donor age, transplant year, diabetes, functional status, and the presence of severe hepatic encephalopathy. Survival was significantly worse with increasing age and decreasing functional status level. There was no significant difference in survival between males and females. Survival improved over the study period, at 5% per calendar year during the first 5 years post transplant, and 1% per year thereafter. CONCLUSIONS: Life expectancies were markedly reduced from normal, even among 5-year survivors with the most favorable characteristics. Survival improved modestly over the years 2002-2018.

Differentiating Depression From Demoralization in Organ Transplantation Recipients.

Living with end stage organ failure and transplantation has implications for physiological, psychological, and social well-being. The development of anxiety or depressive disorders are common with demoralization, another psychological syndrome, a topic of interest in psychiatry. To feel demoralized is to lose hope, courage, or confidence, which upsets normal functioning. While depression may co-exist with demoralization, they are 2 distinct entities, with the former characterized by an inability to experience pleasure and the latter characterized by helplessness and avoidance coping. In an effort to more adequately address the psychological stress in organ transplant patients, it is important to distinguish between demoralization and depression. Demoralization has prognostic implications such as negative disease outcomes such as treatment nonadherence and an increase risk of suicide. Medication for depression is not effective for demoralization syndrome. Therapeutic interventions include cognitive behavioral techniques that focus on exploration of attitudes toward hope and meaning in life.

Disadvantage of Small (<60 kg) Adult Candidates on the Liver Transplantation Waitlist.

BACKGROUND: Small adult patients with lower bodyweight wait-listed for liver transplantation may face a shortage of size-matched whole-liver grafts. The objective of this study is to compare time to transplantation in adult patients with a bodyweight of <60 kg to patients with bodyweight ≥60 kg. METHODS: A matched case-control study was conducted. Patients aged 18 years and older listed for liver transplantation at our transplant center, from 2007 to 2016 with a bodyweight <60 kg were manually matched 1:2 to control patients ≥ 60 kg. Matching was performed based on ABO blood type, model for end-stage liver disease score, (non)-standard exception status, and eligibility for donation after cardiac death. Time to transplantation was assessed with univariable Cox-regression. RESULTS: In total, 23 cases with a bodyweight < 60 kg were matched to 46 average-sized control patients. Small adults were significantly disadvantaged for receiving a liver transplantation as compared to their average-sized counterpart (hazard ratio 0.47; 95% confidence interval 0.29-0.75, P = .002). At the end of follow-up, 14/23 (60.9%) of cases versus 35/46 of controls (76.1%) had received a liver transplantation. CONCLUSION: Small adults with a bodyweight below 60 kg are disadvantaged on the waitlist for a size-matched whole liver graft.

Endovascular transsplenic recanalization with angioplasty and stenting of an occluded main portal vein in an adult liver transplant recipient.

Endovascular transshepatic access has limitations that can be exacerbated in the posttransplantation setting. Although several techniques are available for portal venous system catheterization, the transsplenic approach offers a direct pathway for accessing the portal venous system, as well as associated varices or shunts, while avoiding potential injury to the liver transplant. The purpose of this report is to present the diagnostic and interventional management of main portal vein occlusion in a 56-year-old female after liver transplantation. Endovascular transsplenic recanalization with stenting and shunt embolization is a viable method for treatment of main portal vein thrombosis in an adult liver transplant recipient.

Systematic external evaluation of published population pharmacokinetic models for tacrolimus in adult liver transplant recipients.

BACKGROUND: Diverse tacrolimus population pharmacokinetic (popPK) models in adult liver transplant recipients have been established to describe the PK characteristics of tacrolimus in the last two decades. However, their extrapolated predictive performance remains unclear. Therefore, in this study, we aimed to evaluate their external predictability and identify their potential influencing factors. METHODS: The external predictability of each selected popPK model was evaluated using an independent dataset of 84 patients with 572 trough concentrations prospectively collected from Huashan Hospital. Prediction- and simulation-based diagnostics and Bayesian forecasting were conducted to evaluate model predictability. Furthermore, the effect of model structure on the predictive performance was investigated. RESULTS: Sixteen published popPK models were assessed. In prediction-based diagnostics, the prediction error within ± 30% was below 50% in all the published models. The simulation-based normalised prediction distribution error test and prediction- and variability-corrected visual predictive check indicated large discrepancies between the observations and simulations in most of the models. Bayesian forecasting showed improvement in model predictability with two to three prior observations. Additionally, the predictive performance of the nonlinear Michaelis-Menten model was superior to that of linear one- and two-compartment models with first-order elimination, indicating the underlying nonlinear kinetics of tacrolimus in liver transplant recipients, which was consistent with the findings in adult kidney transplant recipients. CONCLUSIONS: The published models performed inadequately in prediction- and simulation-based diagnostics. Bayesian forecasting may improve the predictive performance of the models. Furthermore, nonlinear kinetics of tacrolimus may be mainly caused by the properties of the drug itself, and incorporating nonlinear kinetics may be considered to improve model predictability.