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Background: Weight gain and obesity are well-known clinical issues in liver transplantation (LTx). However, their impacts on patient outcomes remain unclear, as only the impact of pre-LTx body mass index (BMI) on survival has been meta-analyzed. We summarized and synthesized the evidence on pre- and post-LTx body weight parameters' relations with post-LTx outcomes such as survival, metabolic and cardiovascular comorbidities, and healthcare utilization., Methods: We followed the Cochrane Handbook for Systematic Reviews of Interventions' recommendations. Quality was assessed via a 19-item instrument. Odds ratios and 95% confidence intervals were calculated for outcomes investigated in ≥5 studies., Results: Our meta-analysis included 37 studies. Patients with pre-LTx BMI ≥ 30 kg/m and BMI ≥ 35 kg/m had lower overall survival rates than those with pre-LTx normal weight (72.6% and 69.8% versus 84.2%; P = 0.02 and P = 0.03, respectively). Those with pre-LTx BMI ≥ 30 kg/m had worse overall graft survival than normal weight patients (75.8% and 85.4%; P = 0.003). Pre-LTx BMI and pre-LTx overweight were associated with new-onset diabetes (P < 0.001 and P = 0.015, respectively), but post-LTx BMI showed no relationship. No associations were evident with healthcare utilization., Conclusions: Patients with BMI values ≥30 kg/m had worse patient and graft survival than those with normal weight. Few of the reviewed studies examined post-LTx body weight parameters or other relevant outcomes such as cardiovascular comorbidities. High heterogeneity as well as diverse definitions and operationalizations of measurement and outcomes severely impeded comparability.

Background: Weight gain and obesity can increase liver transplant (LTx) recipients' disease burden. We aimed to summarize and synthesize the evidence on pre- and post-transplant factors related to post-LTx BMI, weight gain, and obesity., Methods: For this systematic review and meta-analysis we searched Medline (PubMed), Cochrane library, CINAHL, PsycINFO, and EMBASE for quantitative studies on 6 classes of factors (i.e., genetic, sociodemographic, behavioral, biomedical, psychological, and environmental) linked to body weight parameters in adult first-time LTx patients. A 19-item instrument was used for quality assessment. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for relationships investigated in ≥5 studies. Factors investigated in <5 studies were summarized and described., Results: Of 16,495 articles retrieved, 43 assessed factors in LTx. These examined 82 mainly biomedical and sociodemographic factors. However, variation between definitions allowed inclusion of only 2 factors (i.e., tacrolimus, cyclosporine) in our meta-analyses of 6 studies examining a shared parameter for body weight (median patient sample: 171 (range: 63-455); Europe n = 3; United States n = 3; publication years: 1997-2015). Neither tacrolimus (OR, 0.75; 95% CI, 0.47-1.21; p = 0.24) nor cyclosporine (OR, 1.40; 95% CI, 0.89-2.18; p = 0.14) were related significantly with post-LTx obesity., Conclusions: Evidence on modifiable factors related to post-LTx body weight parameters is still scarce, as definition variability limits data extraction and pooling for meta-analyses. To facilitate future research, studies should apply theoretical frameworks to guide their study design, select variables of interest and systematically examine interrelationships among selected factors., (Copyright © 2018. Published by Elsevier Inc.)

Weight gain after liver transplantation (LTx) facilitates development of new-onset obesity; however, its risk factors and outcomes are poorly understood. We identified the impact of new-onset obesity on cardiovascular events (CVEs) and patient survival, and risk factors for new-onset obesity. Multiple Cox regression models examined risk factors for CVEs, patient survival, and new-onset obesity in 253 adults (mean age 52.2 ± 11.6 years, male gender 63.6%, mean follow up 5.7 ± 2.1 years). Cumulative incidence of post-LTx CVE was 28.1%; that of new-onset obesity was 21.3%. Regardless of CVE at LTx, post-LTx CVEs were predicted by new-onset obesity [Hazard Ratio (HR), 2.95; P = 0.002] and higher age at LTx (HR, 1.05; P < 0.001). In patients without known pre-LTx CVEs (n = 214), risk factors for post-LTx CVEs were new-onset obesity (HR, 2.59; P = 0.014) and higher age (HR, 1.04; P = 0.001). Survival was not associated with new-onset obesity (P = 0.696). Alcoholic liver disease predicted new-onset obesity (HR, 3.37; P = 0.025), female gender was protective (HR, 0.39; P = 0.034). In 114 patients with available genetic data, alcoholic liver disease (HR, 12.82; P = 0.014) and hepatocellular carcinoma (HR, 10.02; P = 0.048) predicted new-onset obesity, and genetics remained borderline significant (HR, 1.07; P = 0.071). Early introduction of post-LTx weight management programs may suggest a potential pathway to reduce CVE risk., (© 2018 Steunstichting ESOT.)

Background: Well-designed randomized controlled trials (RCTs) testing efficacy of post-transplant medication adherence enhancing interventions and clinical outcomes are scarce., Methods: This randomized controlled trial enrolled adult heart, liver, and lung transplant recipients who were >1 year post-transplant and on tacrolimus twice daily (convenience sample) (visit 1). After a 3-month run-in period, patients were randomly assigned 1:1 to intervention group (IG) or control group (CG) (visit 2), followed by a 6-month intervention (visits 2-4) and a 6-month adherence follow-up period (visit 5). All patients used electronic monitoring for 15 months for adherence measurement, generating a daily binary adherence score per patient. Post-intervention 5-year clinical event-free survival (mortality or retransplantation) was evaluated. The IG received staged multicomponent tailored behavioral interventions (visits 2-4) building on social cognitive theory and trans-theoretical model (e.g., electronic monitoring feedback, motivational interviewing). The CG received usual care and attended visits 1-5 only. Intention-to-treat analysis used generalized estimating equation modeling and Kaplan-Meier survival analysis., Results: Of 247 patients, 205 were randomly assigned (103 IG, 102 CG). At baseline, average daily proportions of patients with correct dosing (82.6% IG, 78.4% CG) and timing adherence (75.8% IG, 72.2% CG) were comparable. The IG had a 16% higher dosing adherence post-intervention (95.1% IG, 79.1% CG; p < 0.001), resulting in odds of adherence being 5 times higher in the IG than in the CG (odds ratio 5.17, 95% confidence interval 2.86-9.38). This effect was sustained at end of follow-up (similar results for timing adherence). In the IG, 5-year clinical event-free survival was 82.5% vs 72.5% in the CG (p = 0.18)., Conclusion: Our intervention was efficacious in improving adherence and sustainable. Further research should investigate clinical impact, cost-effectiveness, and scalability., (Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Short-term patient and graft outcomes continue to improve after kidney and liver transplantation, with 1-year survival rates over 80%; however, improving longer-term outcomes remains a challenge. Improving the function of grafts and health of recipients would not only enhance quality and length of life, but would also reduce the need for retransplantation, and thus increase the number of organs available for transplant. The clinical transplant community needs to identify and manage those patient modifiable factors, to decrease the risk of graft failure, and improve longer-term outcomes.COMMIT was formed in 2015 and is composed of 20 leading kidney and liver transplant specialists from 9 countries across Europe. The group's remit is to provide expert guidance for the long-term management of kidney and liver transplant patients, with the aim of improving outcomes by minimizing modifiable risks associated with poor graft and patient survival posttransplant.The objective of this supplement is to provide specific, practical recommendations, through the discussion of current evidence and best practice, for the management of modifiable risks in those kidney and liver transplant patients who have survived the first postoperative year. In addition, the provision of a checklist increases the clinical utility and accessibility of these recommendations, by offering a systematic and efficient way to implement screening and monitoring of modifiable risks in the clinical setting.

Introduction: Although postoperative delirium (POD) is a common in-hospital complication associated with negative outcomes, evidence in liver transplantation (LT) is scarce., Objective: We examined the incidence and duration of POD, its impact on outcomes and health-care utilization, and described predisposing and precipitating factors favoring POD development., Design: This prospective cohort study included adults undergoing transplantation in a tertiary hospital. Postoperative delirium was assessed 3 times daily until 24 days post-LT, with the Intensive Care Delirium Screening Checklist on the intensive care unit (ICU) and the Delirium Observation Screening Scale on the ward. Postoperative delirium was noted if any of the daily measurements was positive., Results: Forty-two patients (69% male, mean age 55 years, median Model for End-Stage Liver Disease score 15 [interquartile range 8-26]) were included. The incidence of POD was 45.2%, with a median duration of 5 days. Patients with POD had longer ICU (median 8 vs 2 days, P = .000) and hospital stays (median 32 vs 14 days, P = .000) as well as shorter survival (Breslow test P = .045, log-rank test P = .150). Pre-LT comorbidities and perioperative factors might be related to POD development., Conclusion: Nurses are key persons in the detection of POD in the daily clinical routine. The high incidence of POD and its negative association with patient outcomes highlight not only the relevance of systematic assessment of POD after LT but also the need for preventive interventions.

Aim: This was a single-center, mixed-design, cross-sectional and retrospective study to assess the performance of the 4-item, self-reported CAGE (Cut down, Annoyed, Guilty, Eye-opener) questionnaire in predicting histology-proven alcohol-related liver graft injury (ARLGI)., Methods: A total of 316 liver transplant (LT) patients between six months and five years were enrolled. Based on previous research, problem alcohol drinking (PAD) was defined as any score ≥ 1 on the CAGE, while a cut-off of 2 was assumed for alcohol dependence (AD)., Results: Responders were 195, 45 (23.1%) had a CAGE score ≥ 1 and 30 (15.3%) scored ≥ 2. After controlling for confounders, PAD was associated with hyperlipidemia (P=0.01), while AD with a male gender (P=0.01), hyperlipidemia (P=0.03) and alcohol as native diagnosis (P=0.03). PAD and AD were both associated with a significantly higher prevalence of ARLGI, i.e. 53.3% and 63.3%, respectively (P<0.0001). Hepatitis C virus (HCV) patients with PAD showed more steatosis (P=0.04), portal infiltrate (P=0.03), and pericellular/perivenular fibrosis (P=0.02). The likelihood ratios for CAGE scores ranging from 0 to 4 in predicting ARLGI were 0, 5.2, 7.8, 7.8, and 100, respectively., Conclusion: By use of a self-report instrument we found a 23.1% prevalence of PAD and a 15.3% prevalence of AD among LT patients between six months and five years. A variable degree of ARLGI was present in 53.3% of PAD and 63.3% of AD, respectively. HCV patients with PAD had more steatosis, portal inflammation, and pericellular fibrosis. Transplant physicians might improve their ability to predict the probability for ARLGI using the CAGE.

Adherence to medication regimes is crucial for transplant patients. Addressing methodological limitations and gaps in the literature, we studied: (i) the prevalence of nonadherence (NA) with immunosuppression (IS) using various measurement methods, (ii) NA prevalence regarding intake and timing, (iii) changes in NA over time, (iv) differences in NA across organ transplant populations, (v) NA regarding co-medication. Using a descriptive, prospective, comparative design over 3 months, we included convenience samples of adult heart (n=79), liver (n=55), and lung (n=104) transplant patients. NA with IS was measured using self-report, collateral report, blood assay, electronic monitoring (Helping Hand™ , Bang and Olufsen Medicom, Denmark), and their combinations. In the overall sample, depending on the method used, IS NA ranged from 23.9% to 70.0%. For co-medication, the overall NA rate was 30.1% using self-report. Nonadherence rates remained stable over time. At inclusion, significant NA differences between organ groups were reported via self- and collateral report; lung transplant patients were less adherent than heart or liver transplant recipients, both to IS and to co-medication., (© 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.)

The aim of this study was to determine the efficacy, safety, and immunosuppressant adherence in 125 stable liver transplant (LT) patients converted from twice-daily tacrolimus (TAC BID) to once-daily TAC (TAC OD). Tacrolimus trough levels, laboratory parameters, metabolic disorders, selected patient reported outcomes, and adverse events were assessed. Mean TAC trough level concentration was 6.1 ± 2.3 ng/ml at study entry, decreased to 5.5 ± 2.1 ng/ml (P = 0.016) and 5.5 ± 2.2 ng/ml (P = 0.019) after 1 and 2 weeks, respectively, and tended to equal the baseline value during further follow-up. At week 1, TAC concentrations were lower in 62.4% of patients and higher in 36.0% when compared with baseline. Renal and cardiovascular risk factors remained stable and no rejection episodes occurred over 12 months. Adverse events were consistent with the safety profile known from previous studies with TAC BID. Nonadherence measured by the "Basel Assessment of Adherence Scale to Immunosuppressives" was evident in 66.4% at study entry and decreased to 30.9% postconversion (P < 0.0001). Prevalence of nonadherence at baseline was significantly higher in patients converted >2 years after LT and in those ≤60 years of age. Conversion to TAC OD is safe, enhances immunosuppressant adherence and should be accompanied by a close TAC level monitoring during the initial period., (© 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.)

Reports of interventions to improve adherence to medical regimens in solid organ transplant recipients are scarce. A systematic review identified 12 intervention studies. These studies focused on renal, heart, and liver transplant recipients. Five reports used randomized controlled trial (RCT) designs. Sample sizes varied between 18 and 110 subjects. The interventions are difficult to evaluate and categorize because of brief descriptions of intervention details. Of the 12 studies identified in this review, only five studies found a statistically significant improvement in at least one medication-adherence outcome with the intervention. In general, most included a combination of patient-focused cognitive/educational, counseling/behavioral, and psychologic/affective dimensions. Eight studies intervened at the healthcare provider, healthcare setting or healthcare system level, but showed a limited improvement in adherence. No single intervention proved to be superior at increasing medication-adherence in organ transplantation, but a combination of interventions in a team approach for the chronic disease management of organ transplant patients may be effective in a long-term perspective. In conclusion, finding the most effective combination of interventions to enhance adherence is vital. Utilizing an RCT design and adhering to the CONSORT guidelines can lead to higher quality studies and possibly more effective intervention studies to enhance medication-adherence.

Survival outcomes after liver transplantation in adult patients have gradually improved with a five-year survival of about 70% and a ten-year survival of about 60%. The present review focuses on relevant patient-reported outcomes such as self-perceived side effects of immunosuppressive drugs, medication nonadherence and long-term health-related quality of life after liver transplantation. These entities are interrelated but have often been studied separately. Self-perceived symptom experience in liver transplant recipients has not been studied extensively. Symptoms that cause distress differ between men and women, e.g. symptoms related to cosmetic side effects of drugs. Medication nonadherence seems to be infrequent, but if present may have serious consequences. Important risk factors were found to be the costs of drugs, age <40 years, psychiatric disorders, side effects of drugs, beliefs that drugs were harmful, and large influence of the liver transplant on the patient's life. Health-related quality of life is satisfactory, but below the level of the general population. Results, however, must be interpreted with caution as quality-of-life improvements may have been overstated due to variables such as selection bias (e.g. exclusion of severely ill and deceased patients), too many short-term studies, and suboptimal methodology. Presently we lack data on the influence of recurrence of disease, 'de novo' diseases and gender differences on health-related quality of life in liver transplanted patients.

Symptom experience (occurrence and perceived distress) associated with side effects of immunosuppressive medications in organ transplant patients may well be associated with poorer quality of life and medication non-compliance. The aims of this study were: first, to assess symptom experience in clinically stable adult patients during long-term follow-up after liver transplantation; and second, to study the relationship between symptom experience and medication non-compliance. This cross-sectional study included 123 liver transplant patients. Symptom experience was assessed using the "Modified Transplant Symptom Occurrence and Symptom Distress Scale" (29-item version) at the annual evaluation. According to the duration of follow-up, patients were divided into a short-term (1-4 yr) and a long-term (5-18 yr) cohort. Medication non-compliance was measured using electronic monitoring. Results showed that increased hair growth was the most frequent symptom in both sexes. Symptom distress was more serious in women than in men. The most distressing symptom in women was excessive and/or painful periods, while in men this was impotence. Clear differences were revealed at item level between symptom occurrence and symptom distress in relationship with the two time cohorts and between sexes. No relationship was found between symptom experience and prednisolone non-compliance.

Research concerning pretransplant psychosocial and behavioral characteristics in different organ transplant groups is limited. The aim was to assess relevant psychosocial and behavioral pretransplant factors in heart, lung and liver transplant candidates, and their differences among groups. One hundred and eighty-six transplant candidates (i.e. 71 lung, 33 heart and 82 liver) were included (93% response rate). Demographics, clinical variables, co-morbidity, anxiety, depression, personality traits, received social support and adherence with the therapeutic regimen were assessed using validated self-report instruments and chart review. Because of significant differences in gender, age and co-morbidity among groups, analyses were controlled for these factors. Lung (8.2 +/- 4.2) and heart (7.6 +/- 3.5) transplant candidates tended to report more depressive symptoms than liver transplant candidates (6.5 +/- 4.8) (P = 0.05). Groups were comparable for other factors, except for liver transplant candidates being more frequently active smokers (22%) compared with heart (3%) and lung candidates (0%), and more heart (36.4%) and lung candidates (33.3%) drinking alcohol than liver transplant candidates (6.3%). Psychosocial and behavioral characteristics are comparable among pretransplant candidates. Instead of performing the pretransplant psychosocial and behavioral screening in an organ-specific fashion, our data support the use of a more general screening protocol.

Background: Evidence on prevalence and correlates of pretransplant medication nonadherence (MNA) is limited. The present study explored self-reported prevalence and correlates of MNA before heart, liver, and lung transplantation., Methods: This cross-sectional descriptive study included 174 patients: 69 lung, 33 heart, and 72 liver transplant candidates. MNA was assessed by self-report using the following question: "During the past 14 days, how often did you not take your medication?" Patients scoring once or higher on a five-point rating scale were considered to be nonadherent. Correlates of MNA explored were demographics, anxiety and depression (Hospital Anxiety and Depression Inventory), personality traits (NEO Personality Inventory-Revised), perceived health status (Euro-QOL), and social support (Social Support Questionnaire)., Results: Prevalence of pretransplant MNA was 16.7% and was comparable among the three groups. After correction for multiple comparisons (i.e., P=0.01), higher educational level (P=0.006) was related to MNA. Less severe depression (P=0.069), lower scores on the personality trait conscientiousness (P=0.021), and less received social support (P=0.062) tended to be related to MNA. Multiple logistic regression revealed that higher educational level (P=0.008), lower received social support (P=0.013), and lower conscientiousness (P=0.023) were independent predictors of pretransplant MNA., Conclusions: Several correlates of MNA allow identification of patients at risk for pretransplant MNA.

Objective: Even though light to moderate alcohol use might have beneficial effects on health, severe alcohol use is recognized as a major public health concern. Alcohol use has been studied to some extent in solid organ transplant populations, yet, very limited evidence has bee published on alcohol use and its correlates in the renal transplant population. The aim of this study was therefore to determine the prevalence and correlates of alcohol use in renal transplant recipients. Methods: This cross-sectional study is a secondary analysis of the Supporting Medication Adherence in Renal Transplantation (SMART) study. 284 patients were included in this analysis, 58.1% male, mean age: 54.02 y. (SD: 13.34); median years post transplantation 7 (IQR 3-11). The prevalence and frequency of alcohol use as well as the quantity of alcohol consumed were assessed by patient self-report using structured questionnaires. Patients were classified as being at low risk, moderate risk or severe risk based on WHO criteria. Selected psychosocial and behavioral correlates of alcohol use were explored to compare those patients consuming alcohol and those not given the small proportion of patients at risk. Results: 52.8% of the study participants reported to use alcohol. Of the 284 patients included in the analysis, 280 were drinking at low and 3 at moderate risk. However, 1 of the participants drinking at low risk according to WHO criteria was identified as binge drinker. Statistically significant correlates of alcohol use found in univariate analysis were, among others, male gender, current smoking, employment and higher education. In logistic regression analysis, male gender and paid work were found to increase the likelihood of consuming alcohol. Conclusions: Patterns of alcohol use and correlates are comparable to the general population. Severe alcohol use is less prevalent in renal transplant recipients compared to heart and liver transplantation (9% and 6%, respectively), where alcohol is known as an etiological factor in a proportion of patients with end-stage heart or liver disease. [ABSTRACT FROM AUTHOR]