Prehabilitation in patients with cirrhosis awaiting liver transplantation: protocol of a feasibility study.

INTRODUCTION: Patients with cirrhosis awaiting liver transplantation (LT) are often frail, and malnourished. The period of time on the waitlist provides an opportunity to improve their physical fitness. Prehabilitation appears to improve the physical fitness of patients before major surgery. Little is known about prehabilitation in patients with cirrhosis. The aim of this feasibility study will be to investigate the feasibility, safety, and effectiveness of a multimodal prehabilitation programme in this patient population. METHODS AND ANALYSIS: This is an open-label single-arm feasibility trial recruiting 25 consecutive adult patients with cirrhosis active on the LT waiting list of the McGill University Health Centre (MUHC). Individuals will be excluded based on criteria developed for the safe exercise training in patients with cirrhosis. Enrolled individuals will participate in a multimodal prehabilitation programme conducted at the PeriOperative Programme complex of the MUHC. It includes exercise training with a certified kinesiologist (aerobic and resistance training), nutritional optimisation with a registered dietician and psychological support with a nurse specialist. The exercise training programme is divided into an induction phase with three sessions per week for 4 weeks followed by a maintenance phase with one session every other week for 20 weeks. Aerobic training will be individualised based on result from cardiopulmonary exercise testing (CPET) and will include a high-intensity interval training on a cycle ergometer. Feasibility, adherence and acceptability of the intervention will be assessed. Adverse events will be reviewed before each visit. Changes in exercise capacity (6-minute walk test, CPET, liver frailty index), nutritional status and health-related quality of life will be assessed during the study. Post-transplantation outcomes will be recorded. ETHICS AND DISSEMINATION: The research ethics board of the MUHC has approved this study (2021-7646). Our findings will be submitted for presentation at national and international conferences, and for peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT05237583.

Acute kidney injury and chronic kidney disease after liver transplant: A retrospective observational study / Lesión renal aguda y enfermedad renal crónica después de trasplante hepático. Un estudio observacional retrospectivo

Background and rationale: Chronic kidney disease remains an important risk factor for morbidity and mortality among LT recipients, but its exact incidence and risk factors are still unclear.Material and methodsWe carried out a retrospective cohort study of consecutive adults who underwent liver transplant (January 2009–December 2018) and were followed (at least 6 months) at our institution. CKD was defined following the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guidelines. Long-term kidney function was classified into 4 groups: no CKD (eGFR, ≥60mL/min/1.73m2), mild CKD (eGFR, 30–59mL/min/1.73m2), severe CKD (eGFR, 15–29mL/min/1.73m2), and end-stage renal disease (ESRD).ResultsWe enrolled 410 patients followed for 53.2±32.6 months. 39 had CKD at baseline, and 95 developed de novo CKD over the observation period. There were 184 (44.9%) anti-HCV positive, 47 (11.5%) HBsAg positive, and 33 (8.1%) HBV/HDV positive recipients. Recipient risk factors for baseline CKD were advanced age (P=0.044), raised levels of serum uric acid (P<0.0001), and insulin dependent DM (P=0.0034). Early post-transplant AKI was common (n=95); logistic regression analysis found that baseline serum creatinine was an independent predictor of early post-LT AKI (P=0.0154). According to our Cox proportional hazards model, recipient risk factors for de novo CKD included aging (P<0.0001), early post-transplant AKI (P=0.007), and baseline serum creatinine (P=0.0002). At the end of follow-up, there were 116 LT recipients with CKD – 109 (93.9%) and 7 (6.1%) had stage 3 and advanced CKD, respectively. Only two of them are undergoing long-term dialysis.ConclusionThe incidence of CKD was high in our cohort of LT recipients, but only a slight decline in kidney function over time was recorded. Prevention of post-transplant AKI will improve kidney function in the long run. ... (AU)

Antecedentes y justificación: La enfermedad renal crónica (ERC) sigue siendo un importante factor de riesgo de morbimortalidad entre los receptores de un trasplante hepático (TH), su incidencia exacta y sus factores de riesgo aún no están claros.Materiales y métodosLlevamos a cabo un estudio de cohortes retrospectivo de adultos incluidos de forma consecutiva que habían recibido un TH (de enero de 2009 a diciembre de 2018) e hicimos el seguimiento (mínimo 6 meses) en nuestra institución. La ERC se definió siguiendo las guías de práctica clínica Kidney Disease: Improving Global Outcomes (KDIGO) de 2012. La función renal a largo plazo se clasificó en 4 grupos: sin ERC (filtración glomerular estimada [FGe]>60ml/min/1,73m2), ERC leve (FGe: 30-59ml/min/1,73m2), ERC grave (FGe: 15-29ml/min/1,73m2) y enfermedad renal terminal (ERT).ResultadosIncluimos a 410 pacientes a los que se hizo un seguimiento durante 53,2±32,6 meses: 39 tenían ERC al inicio y 95 desarrollaron ERC de novo durante el periodo de observación. Había 184 (44,9%) receptores con anticuerpos contra el VHC, 47 (11,5%) con positividad para el HBsAg y 33 (8,1%) portadores del virus de la hepatitis B (VHB) o el virus de la hepatitis D (VHD). Los factores de riesgo de los receptores para presentar ERC al inicio fueron la edad avanzada (p=0,044), unos niveles elevados de ácido úrico en suero (p<0,0001) y la presencia de diabetes mellitus (DM) insulinodependiente (p=0,0034). La aparición temprana de lesión renal aguda (LRA) postrasplante fue frecuente (n=95); un análisis de regresión logística reveló que la creatinina sérica al inicio era un factor predictivo independiente de LRA temprana después del TH (p=0,0154). Según nuestro modelo de riesgos proporcionales de Cox, los factores de riesgo de los receptores para presentar ERC de novo incluyeron la edad avanzada (p<0,0001), una LRA temprana postrasplante (p=0,007) y la creatinina sérica al inicio (p=0,0002). ...

Impact of MELD 30-allocation policy on liver transplant outcomes in Italy.

BACKGROUND & AIMS: In Italy, since August 2014, liver transplant (LT) candidates with model for end-stage liver disease (MELD) scores ≥30 receive national allocation priority. This multicenter cohort study aims to evaluate time on the waiting list, dropout rate, and graft survival before and after introducing the macro-area sharing policy. METHODS: A total of 4,238 patients registered from 2010 to 2018 were enrolled and categorized into an ERA-1 Group (n = 2,013; before August 2014) and an ERA-2 Group (n = 2,225; during and after August 2014). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of receiving a LT or death between the two eras. The Fine-Gray model was used to estimate the HR for dropout from the waiting list and graft loss, considering death as a competing risk event. A Fine-Gray model was also used to estimate risk factors of graft loss. RESULTS: Patients with MELD ≥30 had a lower median time on the waiting list (4 vs.12 days, p <0.001) and a higher probability of being transplanted (HR 2.27; 95% CI 1.78-2.90; p = 0.001) in ERA-2 compared to ERA-1. The subgroup analysis on 3,515 LTs confirmed ERA-2 (odds ratio 0.56; 95% CI 0.46-0.68; p = 0.001) as a protective factor for better graft survival rate. The protective variables for lower dropouts on the waiting list were: ERA-2, high-volume centers, no competition centers, male recipients, and hepatocellular carcinoma. The protective variables for graft loss were high-volume center and ERA-2, while MELD ≥30 remained related to a higher risk of graft loss. CONCLUSIONS: The national MELD ≥30 priority allocation was associated with improved patient outcomes, although MELD ≥30 was associated with a higher risk of graft loss. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes. CLINICAL TRIAL NUMBER: NCT04530240 LAY SUMMARY: Italy introduced a new policy in 2014 to give national allocation priority to patients with a model for end-stage liver disease (MELD) score ≥30 (i.e. very sick patients). This policy has led to more liver transplants, fewer dropouts, and shorter waiting times for patients with MELD ≥30. However, a higher risk of graft loss still burdens these cases. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes.

Fluorescence spectroscopy for clinical transplantation liver grafts monitoring: possibilities offered by 408 nm excitation

Purpose: Fluorescence spectroscopy techniques have been investigated aiming to reduce the invasiveness of methods for investigation of tissue. In transplantation procedures, it may offer the possibility of a complementary technique for the monitoring of liver grafts' conditions prior to and during the transplantation procedure stages involving cold perfusion. The objective of this study was to evaluate fluorescence spectroscopy under violet light excitation (408 nm) for the monitoring of clinical hypothermic liver transplantation procedures. Methods: Organ grafts were monitored from before the removal of the donor's body to 1 h after the implant into the receptor's body. Fluorescence spectroscopy was assessed over five stages within these transplant stages. Results: The study provided evidence of a correlation between fluorescence information collected during liver grafts transplantation and the survival of patients. Conclusions: Fluorescence spectroscopy can become a tool to monitor transplantation grafts, providing objective information for the final decision of surgeons to use organs.

Tetramethylpyrazine inhibits neutrophil extracellular traps formation and alleviates hepatic ischemia/reperfusion injury in rat liver transplantation.

Hepatic ischemia/reperfusion injury (IRI) is an adverse effect for liver transplantation which is characterized by immune response mediated inflammation. Recent studies report that neutrophil extracellular traps (NETs) are implicated in hepatic IRI. The aim of this study was to explore the mechanism of action of tetramethylpyrazine (TMP), the main chemical composition of Ligusticum chuanxiong in treatment of ischemic related diseases. Data showed that hepatic IRI increases the leak of alanine aminotransferase (ALT) and aspartate transaminase (AST), and stimulates formation of NETs. Extracellular DNA/NETs assay, hematoxylin-eosin (HE) staining, immunofluorescence assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and Western blot assay, showed that TMP significantly reduces formation of NETs and alleviates hepatic IRI. Moreover, TMP and Diphenyleneiodonium (DPI) suppressed ROS production in neutrophils. In addition, analysis showed that activation of NADPH oxidase plays a role in formation of NETs triggered by hepatic IRI. Notably, TMP inhibited formation of NETs though inhibition of NADPH oxidase. Additionally, Combination treatment using TMP and DPI was more effective compared with monotherapy of either of the two drugs. These findings show that combination therapy using TMP and DPI is a promising method for treatment hepatic IRI.

Quality of life 5 years following liver transplantation.

BACKGROUND: Data on quality of life (QOL) among liver transplant recipients from India is scarce. We conducted a prospective assessment of QOL and incidence of complications 5 years following liver transplantation (LT). METHODS: Demographic data of 130 patients (M:F = 98:32, mean age 38.4 ± 14.9 years) who had completed at least 5 years after LT were collected and the incidence of new onset metabolic complications and renal dysfunction was analyzed. Liver transplant database (LTD QOL) questionnaire was given to 100 patients and scoring was done on five QOL domains. This was compared to a historical cohort from the liver transplant database of three transplant centres from North America, who had completed the same questionnaire before and 1 year after LT. RESULTS: The incidence of new onset dyslipidemia, diabetes mellitus, renal dysfunction, hypertension and overweight/obesity was 43%, 26.7%, 25%, 16.4% and 15.4%, respectively. Although ethanol-related cirrhosis was the etiology for transplant in 38%, recidivism was not evident in any recipient in this cohort even after 5 years. Significant improvement in QOL was observed in all five domains, namely measures of disease (p=0.001), psychological status (p=0.001), personal function (p=0.001), social and role function (p=0.001) and general health perception (p=0.001) in our patients 5 years after transplant compared to historical data. CONCLUSION: Although metabolic disease is common after LT, there is significant improvement in long-term QOL. Recidivism appeared to be rare in our study population.

Prehabilitation-Driven Changes in Frailty Metrics Predict Mortality in Patients With Advanced Liver Disease.

INTRODUCTION: Frailty is a predictor of morbidity and mortality in cirrhosis. Although evidence for prehabilitation is promising, the data for liver transplant (LT) candidates are limited. The primary aim of this study was to evaluate the effect of a novel prehabilitation strategy on changes in frailty metrics and survival in LT candidates. The secondary aim was to determine liver-related and extrahepatic conditions associated with frailty. METHODS: In this ambispective cohort study, all patients underwent frailty assessment using the liver frailty index (LFI), 6-minute walk test, and gait speed test performed by a dedicated physical therapist. Home-based exercise prescription was individualized to each patient's baseline physical fitness. RESULTS: We included 517 patients (59% men, median age 61 years, and a model for end-stage liver disease score of 12) evaluated during 936 PT visits. Frailty metrics were affected by age, sex, and liver-related parameters, but not by model for end-stage liver disease. Patients with nonalcoholic fatty liver disease and alcohol-related cirrhosis had worse frailty metrics by all tools. We demonstrated the feasibility of prehabilitation in improving both LFI and 6-minute walk test, particularly in adherent patients. A median LFI improvement of 0.3 in frail patients was associated with improved survival in univariate analysis. Compliance with physical therapist visits (hazards ratio = 0.35 [0.18-0.67] for 2 visits and hazards ratio = 0.54 [0.31-0.94] for ≥3 visits) was independently associated with increased survival. DISCUSSION: Prehabilitation improves frailty metrics in LT candidates and is associated with a survival advantage. Our findings provide a framework for the standardized prehabilitation program in LT candidates while prioritizing compliance, adherence, and on-training LFI goal accomplishment.

Quality of Life and Functional Mobility After Progressive Resistance Exercise in an Adolescent With a Liver Transplant.

PURPOSE: This case report describes physical therapy intervention using progressive resistance exercise (PRE) with the recipient of a liver transplant to improve physical fitness, quality of life, and functional mobility. SUMMARY OF KEY POINTS: Outpatient physical therapy intervention included 2 phases, 10 weeks each, focused on functional training and PRE-based power training and functional tasks. Secondary conditions included excessive weight gain, adjustment disorder, and intensive scarring. STATEMENT OF CONCLUSIONS: PRE-based power training appears to be effective in an adolescent with decreased strength and endurance following liver transplant. Improvements in 1 repetition maximum, functional mobility, aerobic/anaerobic fitness, patient-directed goals, and quality of life were measurable. RECOMMENDATIONS FOR CLINICAL PRACTICE: A PRE-based program may be useful in physical therapy with adolescents after liver transplant. Choice of musculature for training should be relevant to functional limitations and dosing of exercises must be sufficient for muscular hypertrophy.

Challenges for Liver Transplantation During Recovery From the COVID-19 Pandemic: Insights and Recommendations.

The coronavirus disease 2019 (COVID-19) pandemic is placing an increasing burden on liver transplant (LT) services worldwide. At the peak of the pandemic, many LT services worldwide reduced or halted their activities. With the gradual easing of lockdowns, LT teams face new challenges when restarting activities. The numbers of LTs are likely to drop in the immediate post-COVID era. Prolonged and intermittent lockdowns are likely to lead to a shortage of supplies, especially in poor resource settings. Special attention is needed to avoid nosocomial COVID-19 infection among cirrhotic patients awaiting transplant, post-transplant patients, and members of transplant teams. LT programs may have to revise existing strategies in selecting donors and recipients for transplants. Redesigning service provision, restructuring outpatient care, carefully screening and selecting donors and recipients, and performing LT with limited resources will have to be initiated in the post-COVID era if long-term recovery of LT services is to be expected. Costs involved with LT are likely to increase, considering the change in protocols of testing, quarantining, and interstate traveling. This paper discusses the different elements affecting and the widespread impact of the COVID-19 pandemic on LT and strategies to minimize the impact of these factors and to adapt so LT services can meet the health care needs during this pandemic and beyond.

The correlation of patients' anxiety after a liver or kidney transplantation with functional and self-reported work ability.

Organ transplantation has become the treatment of choice for end-stage organ failure, including renal and liver failure. The benefits of patient employment after transplantation are numerous, but factors determining the ability to work among these patients are not clearly defined. The growing interest in these factors has strong practical implications for organizations creating vocational rehabilitation programs. Given the interconnection between psychological and physical functioning in patients after transplantation, the present study examined the impact of anxiety on vocational rehabilitation and its relationship with functional tests. A total of 100 patients after liver or kidney transplantation underwent functional tests, including the 6-minute walking test and 30-second chair stand test (30"CST), and psychological tests, specifically the Inventory of Physical Activity Objectives, Work Ability Index, and State-Train Anxiety Inventory. Working ability was affected by psychological factors. State and trait anxiety exhibited inverse relationships with subjective readiness to occupational activity (P < .001, r = -.59 and P < .001, r = -.56, respectively). The level of anxiety was negatively related to the results of the 30"CST. State-Train Anxiety Inventory, State Anxiety subscale and State-Train Anxiety Inventory, State-Trait Anxiety subscale vs 30"CST: P < .001, r = -.43 P < .001, r = -.44). Thus, state and trait anxiety influence perceived work ability and partially functional status. These observations may indicate the potential benefits of including psychologists in interdisciplinary teams for physical and especially vocational rehabilitation of patients after liver or kidney transplantation.

Transition to Adult Care for Pediatric Liver Transplant Recipients.

In recent years a growing number of pediatric liver transplant recipients are reaching adulthood and are transferred to an adult team. Because pediatric to adult transition has become a common event with many particularities, specific clinical protocols are needed to guide professionals in this process. Transition must be seen as a complex process of high vulnerability for the patient. The incorrect assumption that the transition process is only a bureaucratic transfer of information leads to inappropriate transition procedures that result in young patients not ready to move to adult units with guaranteed success. To ensure this success, a correct coordination and transmission of the information, accompaniment by the health professional during the whole process, and the empowerment of the patient are required. To have a successful transition, a person within the pediatric team must be in charge of the process (named worker).

Brain function and metabolism in patients with long-term tacrolimus therapy after kidney transplantation in comparison to patients after liver transplantation.

BACKGROUND: About 50% of the patients 5-7 years after kidney transplantation show impairment of memory, attention and executive function. Tacrolimus frequently induces neurological complications in the first few weeks after transplantation. Furthermore, tacrolimus treatment is associated with impaired cognitive function in the long-term in patients after liver transplantation. We hypothesize that long-term tacrolimus therapy is associated with cognitive dysfunction and alterations of brain structure and metabolism in patients after kidney transplantation. METHODS: Twenty-one patients 10 years after kidney transplantation underwent cognitive testing, magnetic resonance imaging and whole brain 31-phosphor magnetic resonance spectroscopy for the assessment of brain function, structure and energy metabolism. Using a cross-sectional study design the results were compared to those of patients 1 (n = 11) and 5 years (n = 10) after kidney transplantation, and healthy controls (n = 17). To further analyze the share of transplantation, tacrolimus therapy and kidney dysfunction on the results patients after liver transplantation (n = 9) were selected as a patient control group. RESULTS: Patients 1 and 10 years after kidney transplantation (p = 0.02) similar to patients 10 years after liver transplantation (p<0.01) showed significantly worse cognitive function than healthy controls. In contrast to patients after liver transplantation patients after kidney transplantation showed significantly reduced adenosine triphosphate levels in the brain compared to healthy controls (p≤0.01). Patients 1 and 5 years after kidney transplantation had significantly increased periventricular hyperintensities compared to healthy controls (p<0.05). CONCLUSIONS: Our data indicate that cognitive impairment in the long-term after liver and kidney transplantation cannot exclusively be explained by CNI neurotoxicity.

Exercise Training for Liver Transplant Candidates.

BACKGROUND AND AIMS: Frailty is associated with increased morbidity and mortality, and this is tightly linked to liver decompensation and increased complication rates among liver transplant (LT) candidates. The aim of the study was to evaluate the efficacy of a structured in- and outpatient exercise training program for cirrhotic patients who were referred for liver transplant evaluation. METHODS: We retrospectively reviewed 458 consecutive LT patients. There were 200 patients who underwent LT prior to the implementation of an exercise training program (non-ETP) and 258 LT patients who underwent a comprehensive exercise training program (ETP). Baseline characteristics, readmission rate, and length of hospital stay (LOS) were analyzed and compared between the 2 groups. RESULTS: The ETP group were more likely to have diabetes mellitus and coronary artery disease. However, there was no significant difference in the postoperative complication rates between the 2 groups except for more infections in the ETP group compared to the non-ETP group. There was a trend toward lower 90-day readmission rate in the ETP group (17.9% vs 20%) and shorter LOS (14 vs 17 days). CONCLUSION: There was a trend toward reduced 90-day readmission and shorter length of stay after implementation of an exercise training program.

Physical Condition, Glycemia, Liver Function, and Quality of Life in Liver Transplant Recipients After a 12-Month Supervised Exercise Program.

BACKGROUND AND AIMS: Despite the excellent long-term outcomes in liver transplant (LT) recipients, several medical complications related to lifestyle still represent an issue. This study examined the effects of a 12-month supervised aerobic and strength training program on the aerobic capacity, muscle strength, metabolic profile, liver function, and quality of life of a cohort of LT recipients. METHODS: LT recipients with stable liver function were assigned to interventional exercise (group A) or usual care (group B). Aerobic capacity, muscle strength, metabolic profile, liver and kidney function, and health-related quality of life were assessed at baseline and after 6 and 12 months. Group A attended supervised training sessions 3 times per week for 12 months. Group B received general recommendations about home-based exercise. RESULTS: Forty patients from 6 Italian LT centers were randomized. Twenty-nine (72.5%, men-to-women ratio 23:6, mean age, 52 ± 8 years) LT recipients completed the study. Baseline characteristics were similar between groups except for body mass index and time from LT. No episode of acute rejection nor increase of transaminases occurred. Maximum workload and body mass index increased in both groups over time, but fasting glucose significantly decreased in group A (94.0 ± 15.0 mg/dL vs 90.0 ± 17.0 mg/dL; P = .037) and increased in controls (95.0 ± 24.0 mg/dL vs 102.0 ± 34.0 mg/dL, P = .04). Upper limb muscle strength increased only in supervised LT recipients. Vitality and general and mental health domains significantly improved after physical exercise. CONCLUSIONS: Supervised combined training was safe and effective in increasing aerobic capacity, muscle strength, and quality of life and in improving glucose metabolism in stable LT recipients.

It takes a village: primary care of the pediatric liver transplant recipient.

PURPOSE OF REVIEW: Long-term survival is now the rule rather than the exception for infants and children who undergo liver transplantation for end-stage liver disease, metabolic liver conditions and a variety of other indications. Pediatricians and primary care providers play vital roles in the care and management of this patient population. The purpose of this review is to highlight key aspects important to the care of the pediatric liver transplant recipient. RECENT FINDINGS: Significant advances in immunosuppressive therapies and surgical techniques have contributed to improved graft and patient survival rates, shifting the focus beyond immediate survival to strategies to minimize comorbidities related to long-term immunosuppression during growing years, attend to patient and parent-reported outcomes and enhance quality of life. A multidisciplinary approach allows for monitoring and surveillance of both routine (growth, nutritional rehabilitation, cognitive development, mental and psychosocial health, contraception and daily activities) and transplant-related (adverse effects of immunosuppression, susceptible infections, extra-hepatic systems, transition from childhood to adolescence to adulthood) themes. SUMMARY: Effective communication between the primary care physician and the transplant team is imperative for optimizing best outcomes. The primary care provider should be aware of the multifacet nature of posttransplant management, which includes medication regimens, common complications and infections.

'Back to Life'-Using knowledge exchange processes to enhance lifestyle interventions for liver transplant recipients: A qualitative study.

AIM: Interventions to prevent excessive weight gain after liver transplant are needed. The purpose of the present study was to enhance a specialist post-transplant well-being program through knowledge exchange with end-users. METHODS: The study used an interactive process of knowledge exchange between researchers, clinicians and health system users. Data were collected as focus groups or telephone interviews and underwent applied thematic analysis. RESULTS: There were 28 participants (age 24-68 years; 64% male). The results identified experiences that may influence decisions around health behaviours during the course of transplant recovery. Three over-arching themes were identified that impact on liver transplant recipients post-transplant health behaviours. These include (i) Finding a coping mechanism which highlighted the need to acknowledge the significant emotional burden of transplant prior to addressing long-term physical wellness; (ii) Back to Life encompassing the desire to return to employment and prioritise family, while co-ordinating the burden of ongoing medical monitoring and self-management and (iii) Tailored, Personalised Care with a preference for health care delivery by transplant specialists via a range of flexible eHealth modalities. CONCLUSIONS: This person-centred process of knowledge exchange incorporated experiences of recipients into service design and identified life priorities most likely to influence health behaviours post-transplant. Patient co-creation of services has the potential to improve the integration of knowledge into health systems and future directions will require evaluation of effectiveness and sustainability of patient-centred multidisciplinary service development.

Stem Cell-Based Therapies for Liver Diseases: An Overview and Update.

BACKGROUND: Liver disease is one of the top causes of death globally. Although liver transplantation is a very effective treatment strategy, the shortage of available donor organs, waiting list mortality, and high costs of surgery remain huge problems. Stem cells are undifferentiated cells that can differentiate into a variety of cell types. Scientists are exploring the possibilities of generating hepatocytes from stem cells as an alternative for the treatment of liver diseases. METHODS: In this review, we summarized the updated researches in the field of stem cell-based therapies for liver diseases as well as the current challenges and future expectations for a successful cell-based liver therapy. RESULTS: Several cell types have been investigated for liver regeneration, such as embryonic stem cells, induced pluripotent stem cells, liver stem cells, mesenchymal stem cells, and hematopoietic stem cells. In vitro and in vivo studies have demonstrated that stem cells are promising cell sources for the liver regeneration. CONCLUSION: Stem cell-based therapy could be a promising therapeutic method for patients with end-stage liver disease, which may alleviate the need for liver transplantation in the future.

Self-management in liver transplantation.

BACKGROUND: Self-management is crucial for liver transplant (LT) recipients to maintain transplants and optimize health outcomes. However, previous literature has been primarily limited to examining medication adherence; there is a knowledge gap regarding self-management in the LT population. AIM: The aims of this study were to 1) comprehensively describe self-management behaviors and activities in LT recipients, 2) explore levels of overall self-management, and 3) explore the relationships of self-efficacy, cognition, and health information seeking behavior with self-management. METHODS: Adult LT recipients (n = 113) who had a functioning transplant for at least 6 months participated in this cross-sectional, descriptive study. Participants were asked to identify self-management behaviors and rate their performance of those behaviors, including symptom management and medication adherence. They also completed a cognitive assessment and questionnaires measuring self-efficacy and health information seeking behavior. Descriptive statistics, latent profile analysis, and probit model for path analysis were used for the data analysis. RESULTS: LT recipients acknowledged engaging in various self-management behaviors including symptom management, physical activity, maintenance of positive attitudes, and communication with healthcare providers. Three levels of self-management (i.e., low, medium, and high) were found; a high level of self-management was related to self-efficacy and health information seeking behavior. CONCLUSIONS: The findings indicate that self-management may be improved with interventions aimed at increasing self-efficacy and health information seeking behavior. Findings from this study will inform future interventions, to improve self-management and subsequent health outcomes in this population. Future longitudinal studies are necessary to confirm the causality of the identified relationships.

Variability in intensive care unit length of stay after liver transplant: Determinants and potential opportunities for improvement.

PURPOSE: Recovery after liver transplant (LT) requires extensive resources, including prolonged intensive care unit stays. The objective of this study was to use an assessment tool to determine if LT recipients remain in ICU beyond designated indications. METHODS: Records from 100 consecutive LTs performed in a single institution were retrospectively reviewed. An admission, discharge, and triage screening (ADT) tool was utilized to assess the indications for each ICU day. Data collected included demographics; pre-, intra-, and post-operative course; and complications. Days not meeting ADT criteria were considered additional ICU days. RESULTS: 100 patients: mean age 55 years (range 24-78 years) and mean MELD score 30 (range 6-47). Three recipients who died within one week were excluded. Forty-eight (49.5%) patients had a total of 75 additional days on initial ICU stay. Univariate analysis revealed no significant differences between patients with and without additional days. 12/97 (12.4%) patients returned to ICU including 5/48 and 7/49 with and without additional days. CONCLUSION: Nearly half of the LT recipients remained in ICU an average of 1.6 additional days. Monitoring of organ function appeared to be the most common reason. Opportunities to improve resource utilization could include transfer to an intermediate/progressive care ("step-down") unit.

Potential savings in the treatment pathway of liver transplantation: an inter-sectorial analysis of cost-rising factors.

INTRODUCTION: Identification of cost-driving factors in patients undergoing liver transplantation is essential to target reallocation of resources and potential savings. AIM: The aim of this study is to identify main cost-driving factors in liver transplantation from the perspective of the Statutory Health Insurance. METHODS: Variables were analyzed with multivariable logistic regression to determine their influence on high cost cases (fourth quartile) in the outpatient, inpatient and rehabilitative healthcare sectors as well as for medications. RESULTS: Significant cost-driving factors for the inpatient sector of care were a high labMELD-score (OR 1.042), subsequent re-transplantations (OR 7.159) and patient mortality (OR 3.555). Expenditures for rehabilitative care were significantly higher in patients with a lower adjusted Charlson comorbidity index (OR 0.601). The indication of viral cirrhosis and hepatocellular carcinoma resulted in significantly higher costs for medications (OR 21.618 and 7.429). For all sectors of care and medications each waiting day had a significant impact on high treatment costs (OR 1.001). Overall, cost-driving factors resulted in higher median treatment costs of 211,435 €. CONCLUSIONS: Treatment costs in liver transplantation were significantly influenced by identified factors. Long pre-transplant waiting times that increase overall treatment costs need to be alleviated by a substantial increase in donor organs to enable transplantation with lower labMELD-scores. Disease management programs, the implementation of a case management for vulnerable patients, medication plans and patient tracking in a transplant registry may enable cost savings, e.g., by the avoidance of otherwise necessary re-transplants or incorrect medication.