Exercise prehabilitation is an evidence-based, safe, and effective method to increase quality of life, physical fitness and function, and post-surgical outcomes in solid organ transplant (SOT) patients. However, few prehabilitation programs for SOT patients exist in practice. Furthermore, there is a lack of multimodal prehabilitation programs that include behavior change support. To address this need, the Transplant Wellness Program (TWP) was designed.

The objective of the TWP is to assess both the effectiveness and implementation of a comprehensive and multimodal exercise and wellness behavior change intervention for patients undergoing kidney or liver transplant.

The TWP is a hybrid effectiveness-implementation trial consisting of exercise and wellness behavior change support.

Individuals who are in evaluation or listed for kidney or liver transplant in Southern Alberta, Canada.

The primary outcomes of self-reported exercise and quality of life are assessed at intake, post-exercise intervention, 6 months post-intake, 12 weeks post-transplant, and annually for 5 years after program completion. Functional fitness measures will be assessed at intake, post-exercise intervention, 12 weeks post-transplant, 6 months post-intake, and 1-year post-intake. The reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework is used to determine the impact of TWP at the individual and health care system level.

Recruitment began in November 2023 and will continue until November 2028. Participants take part in a 12-week exercise intervention and are offered individualized and group behavior change support. Continued exercise support is offered through maintenance classes after the completion of the 12-week intervention.

The design of the hybrid effectiveness-implementation trial with a single experimental group will not allow for comparisons to a control or usual care group, potentially impacting internal validity. Differences in number of participants between organ groups (kidney vs liver) and cohorts (pre-transplant vs post-transplant) will likely be uneven, requiring consideration when running and interpreting analyses.

The TWP aims to support patients throughout the transplant journey through a multimodal and comprehensive exercise and wellness behavior change program. Results from this study will determine the effectiveness of the program and inform future scale-up and sustainability.

NCT06367244.

Frailty in patients with cirrhosis is associated with increased morbidity and mortality. In this study, we aimed to determine the prevalence of frailty and its impact on mortality and hospitalization in patients with cirrhosis.

An elaborate search was undertaken in the databases "PubMed, Scopus, Web of Science, and Cochrane, and preprint servers", and an assessment of all published articles till 17 February 2023 was done. Studies that provided data on prevalence, mortality and hospitalization among frail patients with cirrhosis were included. The study characteristics and data on the prevalence, mortality, and hospitalization were extracted from included studies. The primary outcome was to estimate the pooled prevalence of frailty and determine its impact on mortality and hospitalization in patients with cirrhosis.

Overall, 12 studies were included. Data on prevalence of frailty and mortality were available in 11 studies, while seven studies reported data on hospitalization. The analysis conducted among 6126 patients with cirrhosis revealed pooled prevalence of frailty to be 32% (95% confidence interval [CI], 24-41). A total of 540 events of death revealed a pooled mortality rate of 29% (95% CI, 19-41). Six-month and twelve-month pooled estimates of mortality were found to be 24% (95% CI, 17-33) and 33% (95% CI, 23-45), respectively. The pooled hospitalization rate among the seven studies was 43% (95% CI, 21-68).

The prevalence of frailty in patients with cirrhosis is high, leading to poor outcomes. Frailty assessment should become an integral part of cirrhosis evaluation.

PROSPERO 2022 CRD42022377507.

Research on the association between activity levels and sedentary behaviour with frailty in patients affected by hepatitis B cirrhosis is sparse. This study aimed to explore the association of frailty with activity levels and sedentary behaviours in patients with hepatitis B cirrhosis.

This cross-sectional study followed the STROBE checklist.

This study was conducted in Guangzhou, China, between August 2021 and October 2022. The frailty condition of patients with hepatitis B cirrhosis was assessed using the liver frailty index (LFI). Their physical activity levels and sedentary time were assessed using the International Questionnaire of Physical Activity. Pearson correlation and binary logistic regression were used to analyse the data.

Among the 503 patients with hepatitis B cirrhosis in the final analysis, 107 (21.3%) were identified as frail. Frailty was negatively correlated with walking time (r = -0.174, p < 0.001), moderate-intensity activity time (r = -0.185, p < 0.001), high-intensity activity time (r = -0.243, p < 0.001) and total activity time (r = -0.256, p < 0.001). Patients with insufficient activity (<150 min/week) and sedentary behaviour (≥420 min/day) were found to have 2.829 times higher risk of frailty than those with sufficient activity (≥150 min/week) and no sedentary behaviour (<420 min/day) (95% CI: 1.380, 5.799).

Patients with hepatitis B cirrhosis who exhibited frailty demonstrated limited physical activity and engaged in sedentary behaviours.

Patients with hepatitis B cirrhosis contributed their data to the study.

It is not known which of the 5 components of the Fried frailty score have the most predictive value for outcomes in simultaneous pancreas-kidney transplant (SPK) and solitary pancreas transplant (SPT) recipients.

In this study, we sought to investigate the association between pretransplant overall frailty and individual frailty components, with posttransplant outcomes among SPK and SPT recipients. Outcomes of interest were length of stay, kidney delayed graft function (K-DGF), readmission within 30 d after discharge, cardiovascular events, acute rejection, pancreas death-censored graft failure (DCGF), kidney DCGF, and death.

Of the individual frailty components among SPK (n = 113), only slow walk time was associated with an increased risk of mortality (adjusted odds ratio [aOR]: 4.99; P = 0.03). Among SPT (n = 49), higher sum frailty scores (coefficient correlation 0.29; P = 0.04) and weight loss (coefficient correlation  = 0.30; P = 0.03) were associated with prolonged length of stay. Similarly, weight loss among SPT was associated with an increased risk of DCGF (aOR: 4.34; P = 0.049). Low grip strength was strongly associated with an increased risk of early readmission (aOR: 13.08; P = 0.008).

We found that not all components of frailty contribute equally to predicting outcomes. Objective measurements of slow walk time, unintentional weight loss, and low grip strength were found to be associated with less optimal outcomes in pancreas transplant recipients. Targeted interventions may improve posttransplant outcomes.

Frailty corresponds to an emerging construct in the hepatology which is originally introduced as a validated geriatric syndrome regarding increased vulnerability to pathophysiological stressors. As for patients with cirrhosis, the presence of frailty is indicative of debilitating conditions that subjects are prone to deleterious acute insults and have difficulties to restore even if the underlying liver function partially returned to normal levels. Since this conceptual development, a variety of tools assessing frailty have been proposed and evaluated in the context of cirrhosis. A recent performance-based metric for frailty, designated as Liver Frailty Index, has broadly been applied in patients with cirrhosis and exhibited acceptable predictive ability in relation to disease progression, mortality and hospitalization. However, those functional tests measuring frailty may be impossible to perform in circumstance that patients are critically ill or undergoing detrimental events. An interesting modality indicates the use of alternative tests to evaluate frailty, which may be more adaptable and of choice for specific subgroups. The interrelation between frailty and various cirrhosis-associated pathological entities is of clinical importance and implication. Noticeably, it is imperative to clarify these complex linkages to highlight novel therapeutic targets or interventional endpoints. The efficient and effective management of frailty is still challenging, but many attempts have been made to overcome barriers of affordability and availability. Some clinical trials on small scale revealed that home-based exercise and individualized nutrition therapy show benefits in patients with cirrhosis, and high adherence to the treatment regimen may direct better efficacy and performance.

The concept of frailty has gained importance, especially in patients with liver disease. Our study systematically investigated the effect of frailty on post-procedural outcomes in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS).

We used National Inpatient Sample(NIS) 2016-2019 data to identify patients who underwent TIPS. Hospital frailty risk score (HFRS) was used to classify patients as frail (HFRS>=5) and non-frail (HFRS<5). The relationship between frailty and outcomes such as death, post-procedural shock, non-home discharge, length of stay (LOS), post-procedural LOS, and total hospitalization charges (THC) was assessed.

A total of 13,700 patients underwent TIPS during 2016-2019. Of them, 5,995 (43.76%) patients were frail, while 7,705 (56.24%) were non-frail. There were no significant differences between the two groups based on age, gender, race, insurance, and income. Frail patients had higher mortality (15.18% vs. 2.07%, p<0.001), a higher incidence of non-home discharge (53.38% vs. 19.08%, p<0.001), a longer overall LOS (12.5 days vs. 3.35,p<0.001), longer post-procedural stay (8.2 days vs. 3.4 days, p<0.001), and higher THC ($240,746.7 vs. $121,763.1, p<0.001) compared to the non-frail patients. On multivariate analysis, frail patients had a statistically significant higher risk of mortality (aOR-3.22, 95% CI-1.98- 5.00, p<0.001).

Frailty assessment can be beneficial in risk stratification in patients undergoing TIPS.

The majority of patients with decompensated cirrhosis suffer from malnutrition, a potentially modifiable contributor to frailty and sarcopenia. The present study investigated the impact of a 6-month dietician-supported home-based intensive nutrition therapy (HINT) intervention on objective frailty and sarcopenia metrics in patients with decompensated cirrhosis.

One hundred adult patients with decompensated cirrhosis, frailty, and sarcopenia at baseline were randomized 1:1 to receive standard medical therapy (SMT) plus HINT (intervention) versus SMT (control) alone. The primary outcome was an improvement in frailty as measured by the liver frailty index (LFI). Secondary outcome measures included sarcopenia metrics, liver disease severity scores, hospitalization, and death.

The LFI improved more in the intervention arm as compared with controls (0.8 vs 0.4; P < 0.001). Baseline and end-of-study skeletal muscle index (SMI) was available in a subset of 32 male patients, with greater improvements seen in the intervention arm compared with controls (6.36 vs 0.80; P = 0.02). Patients in the intervention arm had less hospitalizations over the 6-month follow-up (19 [38%] vs 29 [58%]; P = 0.04). On subgroup analysis, in the 64% of patients who were adherent to calorie and protein intake targets at 6 months, significant improvement was seen in liver disease severity scores and survival (P < 0.05).

In patients with decompensated cirrhosis, frailty, and sarcopenia, a 6-month dietitian-supported home-based intensive outpatient nutrition therapy was associated with statistically and clinically relevant improvement in frailty. The subgroup of adherent patients showed improvement in their liver disease scores and reduction in mortality. These findings support the key role of food as medicine in the management of cirrhosis.

Liver transplantation is the most important therapeutic intervention for end-stage liver disease (ELD). The prioritization of these patients is based on the model for end-stage liver disease (MELD), which can successfully predict short-term mortality. However, despite its great validity and value, it cannot fully incor porate several comorbidities of liver disease, such as sarcopenia and physical frailty, variables that can sufficiently influence the survival of such patients. Subsequently, there is growing interest in the importance of physical frailty in regard to mortality in liver transplant candidates and recipients, as well as its role in improving their survival rates.

To evaluate the effects of an active lifestyle on physical frailty on liver transplant candidates.

An observational study was performed within the facilities of the Department of Transplant Surgery of Aristotle University of Thessaloniki. Twenty liver tran splant candidate patients from the waiting list of the department were included in the study. Patients that were bedridden, had recent cardiovascular incidents, or had required inpatient treatment for more than 5 d in the last 6 mo were excluded from the study. The following variables were evaluated: Activity level via the International Physical Activity Questionnaire (IPAQ); functional capacity via the 6-min walking test (6MWT) and cardiopulmonary exercise testing; and physical frailty via the Liver Frailty Index (LFI).

According to their responses in the IPAQ, patients were divided into the following two groups based on their activity level: Active group (A, 10 patients); and sedentary group (S, 10 patients). Comparing mean values of the recorded variables showed the following results: MELD (A: 12.05 ± 5.63 vs S: 13.99 ± 3.60; P > 0.05); peak oxygen uptake (A: 29.78 ± 6.07 mL/kg/min vs S: 18.11 ± 3.39 mL/kg/min; P < 0.001); anaerobic threshold (A: 16.71 ± 2.17 mL/kg/min vs S: 13.96 ± 1.45 mL/kg/min; P < 0.01); 6MWT (A: 458.2 ± 57.5 m vs S: 324.7 ± 55.8 m; P < 0.001); and LFI (A: 3.75 ± 0.31 vs S: 4.42 ± 0.32; P < 0.001).

An active lifestyle can be associated with better musculoskeletal and functional capacity, while simultaneously preventing the evolution of physical frailty in liver transplant candidates. This effect appears to be independent of the liver disease severity.

The purpose of this manuscript is to identify the pathophysiology of the metabolic abnormalities observed in cirrhosis and to uncover associations, if any, to its complications, such as sarcopenia and hepatic encephalopathy (HE).

Liver dysfunction in cirrhosis is known to be a precipitating factor in the disruption of many physiological pathways, specifically nutrient metabolism. As a result, affected patients are highly susceptible to derangements of processes affecting multiple classes of macro- and micronutrients, including proteins, carbohydrates, electrolytes, vitamins, and minerals. These disruptions are thought to be contributory to the pathogenesis of known complications of cirrhosis.

Literature research of relevant topics was conducted for the above stated objective; sources were limited to articles from peer-reviewed journals published within the last 30 years.

This research established that there is positive correlation between nutrient derangements and the increased risk of complications of cirrhosis, which themselves carry significant morbidity and mortality risk. It also established that some nutrient and electrolyte abnormalities are independent indicators of prognosis and adverse outcomes, such as mortality. This also highlights the importance of comprehension of anomalous metabolism and its complications as it necessitates serious consideration in clinical care. In addition to medical management, cirrhotic patients also require ancillary assessment, such as comprehensive nutritional evaluation, to identify and treat reversible nutritional derangements. This consideration provides the best opportunity to achieve maximal health outcomes in the cirrhotic patient population.

Liver cirrhosis results in progressive decline, or frailty, which leads to poor outcomes and decreased survival. Multiple biomarkers and clinical assessment tools for quantifying frailty in liver transplant candidates exist, but a universal scoring protocol is lacking. Criteria vary between studies and correlation with patient outcome is not always clear. This review aims to summarize the pertinent biomarkers and assessment tools of frailty in cirrhosis.

As cirrhosis progresses, the resultant 'frailty' is an inseparable independent predictor of pre and posttransplant mortality. Pro-inflammatory, neuroendocrine, and adipokine factors are dysregulated - leading to paradoxical anorexia and downregulation of orexigenic signals. The resulting catabolic utilization of amino and fatty acids leads to progressive malnutrition and sarcopenia. Both functional and imaging criteria define sarcopenia in cirrhotic patients, and degree of debilitation correlates with mortality. Liver-disease-specific frailty biomarkers and scoring tools are optimal to assess physical dysfunction in cirrhotics to promote early diagnosis and intervention.

Liver cirrhosis and resulting frailty are progressive and portend a poor patient prognosis. A comprehensive, validated algorithm for detecting and quantifying frailty specific to liver disease would allow for standardization and facile application in the clinical setting. Early diagnosis is key for timely intervention and improved patient outcomes.

There are a variety of definitions and criteria used in clinical practice to define frailty. In the absence of a gold-standard definition, frailty has been operationally defined as meeting 3 out of 5 phenotypic criteria indicating compromised function: low grip strength, low energy, slowed walking speed, low physical activity, and unintentional weight loss. Frailty is a common problem in solid organ transplant candidates who are in the process of being listed for a transplant, as well as after transplantation. Patients with diabetes or chronic kidney disease (CKD) are known to be at increased risk of being frail. As pancreas transplantation is exclusively performed among patients with diabetes and the majority of them also have CKD, pancreas transplant candidates and recipients are at high risk of being frail. Sarcopenia, fatigue, low walking speed, low physical activity, and unintentional weight loss, which are some of the phenotypes of frailty, are very prevalent in this population. In various solid organs, frail patients are less likely to be listed or transplanted and have high waitlist mortality. Even after a transplant, they have increased risk of prolonged hospitalization, readmission, and delayed graft function. Given the negative impact of frailty on solid organ transplants, we believe that frailty would have a similar or even worse impact on pancreas transplantation. Due to the paucity of data specifically among pancreas transplant recipients, here we include frailty data from patients with CKD, diabetes, and various solid organ transplant recipients.

Patients with liver cirrhosis and, in particular, those with liver failure are at high risk of reduced muscle mass and strength/function, otherwise known as sarcopenia. Sarcopenia is a complex, multifactorial (poor nutritional intake, protein catabolism, physical inactivity) chronic condition, which increases the risk of liver-related morbidity and mortality. Early recognition and tailored management incorporating high protein diets and combination aerobic/resistance exercise can ameliorate the complications associated with sarcopenia in cirrhosis. This review provides an overview of the epidemiology, pathogenesis, assessment tools and management of sarcopenia in cirrhosis.

Liver cirrhosis leads to autonomic dysfunction (AD). We present a pilot study and review of published literature to investigate the long-term changes in the Autonomic Nervous System (ANS) of patients who underwent liver transplant. We propose Autonomic Function Tests (AFT) can be used as a predictor of liver transplant outcome.

Twenty-eight patients (19 men and 9 women; mean age 45 years) with cirrhosis due to different etiologies underwent a noninvasive ANS evaluation test, pre- and post-liver transplant at 3 to 6 months, 8 to 12 months, and 14 to 24 months. Data were compared with 45 age-matched controls (14 men and 31 women). We investigated changes in the following 3 adrenergic measures: percentage of cutaneous vasoconstriction in the hand and foot in response to cold stress test and cutaneous blood flow adjustment ratio; and 3 cardiovagal measures: change in heart rate in relation to deep respiration, forced respiration represented as Valsalva Ratio, and head-up tilting (30/15 ratio).

A total of 23 of 28 patients (82%) had impairment in AFT before transplant, 16 of 28 (57%) in the sympathetic adrenergic measures, and 15 of 28 (54%) in the parasympathetic cardiovagal measures. There was a gradual improvement in ANS function posttransplant, with a significant improvement in the cardiovagal measure of Valsalva Ratio (P < .05 from baseline). These data suggest some temporary decline in ANS functions within the first 6 months posttransplant.

To optimize outcomes in liver transplant patients with autonomic dysfunction, autonomic testing perhaps combined with frailty testing can be used as objective measures of mortality in the pre-liver transplant stage.