Cirrhosis Awaiting Liver Transplantation Research Articles

Frailty and sarcopenia in patients with cirrhosis awaiting liver transplantation: evidence from a single-centre, prospective cohort study.

Sarcopenia and frailty are common complications in patients with cirrhosis evaluated for liver transplantation (LT). Although the negative impact of sarcopenia on patient's outcome has been well studied, the prognostic role of frailty is not as clear. We assessed the prevalence of sarcopenia and frailty and the clinical impact of frailty in a prospective cohort of cirrhosis patients with and without hepatocellular carcinoma (HCC) listed for LT. Patients with cirrhosis were prospectively recruited at the time of admission into the waiting list. Clinical and lab values were collected. Physical frailty was assessed by liver frailty index (LFI) and patients were categorized into robust (< 3.2); pre-frail (between 3.2 and 4.5), and frail (> 4.5). Skeletal muscle mass was evaluated via skeletal muscle index (SMI) obtained from last CT scan before LT; sarcopenia was defined by SMI < 50 cm2/m2 in males and < 39 cm2/m2 in females. 105 patients were included, of which 42 (40%) had hepatocellular carcinoma (HCC). In patients without HCC (63.5% males, median age 61 years), 36.5% were frail, 50.8% were pre-frail and 12.7% were robust. Frail patients were older than non-frail patients (63 vs. 56; p = 0.008) and had more severe liver disease (Child C: 65% vs. 37.5%; p = 0.02). Prevalence of sarcopenia in patients without HCC was 63%, with similar value of median SMI between frail and not frail patients (p = 0.454). Patients with HCC (78.6% males, 65years old) were 21.4% frail, 61.9% pre-frail, and 16.7% robust. Frail patients had more severe liver disease (Child C: 77% vs. 18.2%; p = 0.004), whereas age was comparable to non-frail patients; among patients without HCC, during a median follow-up of 263days, 17% died (of which 72% were frail) and 10 patients were delisted due to clinical improvement (none of whom were frail). Among those with HCC, during a median follow-up of 289 days, 4 (9%) patients died of which 50% were frail. Frailty and sarcopenia are common complications in patients with cirrhosis awaiting LT. Frailty appears to be associated with an increased risk of mortality during wait-list time especially in those with decompensated cirrhosis. At univariate analysis Meld score, Child score and presence of frailty were found to be associated with shorter survival, however, at multivariate analysis presence of frailty and Child C vs. A/B were the only independent predictor of death. Larger cohorts are required to confirm these results.

Impact of acute kidney injury response on survival and liver transplant rates in hospitalized patients with cirrhosis awaiting liver transplantation: Results from the HRS-HARMONY consortium.

Acute kidney injury (AKI) frequently complicates the course of hospitalized patients with cirrhosis and negatively affects their prognosis. How AKI response influences the timing of liver transplantation (LT) remains unclear. We sought to assess the impact of AKI response to treatment on survival and LT rates in cirrhosis patients awaiting LT. This was a retrospective multicenter study of cirrhosis patients waitlisted for LT and hospitalized with AKI in 2019. The exposure was AKI response versus no response during hospitalization. Outcomes were 90-day overall and transplant-free survival, and rates of LT with time to transplant. We adjusted for age, sex, race, cirrhosis etiology, site, and MELD-Na score. Among the 317 patients in this study, 170 had AKI response (53.6%), and 147 had no response (46.4%). Compared to non-responders, responders had better 90-day overall survival (89.4% vs. 76.2%, adjusted sHR for mortality 0.34, p=0.001), and transplant-free survival (63.5% vs. 25.2%, aHR for probability of death or transplant 0.35, p<0.001). The LT rate was lower in responders (45.9% vs. 61.2%, adjusted sHR 0.55, p=0.005). 79% of transplants in responders occurred after discharge, at a median of 103 days, while 62% of transplants in non-responders occurred during hospitalization, with the remainder occurring post-discharge at a median of 58 days. In patients with cirrhosis waitlisted for LT who are hospitalized with AKI, AKI response to therapy is associated with improved 90-day survival, despite a reduced LT rate and longer time to LT.

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

IntroductionPatients 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...

Nutritional aspects of prehabilitation in adults with cirrhosis awaiting liver transplant.

Malnutrition, sarcopenia (low muscle mass), and physical frailty have gained increasing recognition in candidates for liver transplant (LT) as these conditions can impact postoperative functional capacity. Multidimensional prehabilitation programs have been proposed as a safe intervention in adults awaiting LT but the nutritional pillar of prehabilitation has been understudied. This review summarizes the nutritional recommendations for prehabilitation for individuals with cirrhosis awaiting LT. Three major aspects of nutritional prehabilitation are discussed: (1) Assess: Evaluate nutritional status and assess for malnutrition, sarcopenia, and frailty to guide the nutritional prehabilitation intervention intensity, increasing across universal, targeted, and specialist levels; (2) Intervene: Prescribe a nutritional prehabilitation intervention to meet established nutrition guidelines in cirrhosis with a targeted focus on improving nutritional status and muscle health; (3) Reassess: Follow-up based on the required intensity of nutritional care with as needed intervention adjustment. Topics covered in the review include nutritional care levels for prehabilitation, energy prescriptions across body mass index strata, detailed considerations around protein intake (amount, distribution, and quality), carbohydrate and fat intake, other nutritional considerations, and the potential role of dietary supplements and nutraceuticals. Future research is warranted to more accurately evaluate energy needs, evaluate emerging dietary supplementation strategies, and establish the role of nutraceuticals alongside food-based interventions. While the general principles of nutritional prehabilitation are ready for immediate application, future large-scale randomized controlled trials in this space will help to quantify the benefit that can be gained by transitioning the LT approach from passive "transplant waitlist time" to active "transplant preparation time."

Nonselective beta-blockers may lead to stage 2 acute kidney injury and waitlist mortality in child class C cirrhosis.

Nonselective beta-blockers (NSBB) protect patients with compensated cirrhosis; however, it is unclear if NSBB is associated with acute kidney injury (AKI) in patients with decompensated cirrhosis. We aimed to determine if the use of NSBB was associated with an increased risk of stage II AKI or greater and waitlist mortality (WLM) among patients with decompensated cirrhosis awaiting liver transplant stratified by cirrhosis severity. Included were 1816 outpatients listed for liver transplantation at UCSF from June 2012 to April 2022. Our primary outcome was stage 2 AKI (>200% increase in serum creatinine). Our secondary outcome was WLM (all-cause mortality). Our primary exposure was the use of any NSBB derived using natural language processing of clinical notes. Multivariable Cox proportional hazards models with time-dependent variables were used to determine the HR of NSBB use on stage 2 AKI and WLM, stratified by Child-Pugh Score. The average age of the cohort was 58 years old, with 35% identifying as female. In multivariable time-dependent models, NSBB use was associated with 1.53 × (95 CI 1.19-1.97) the hazard of stage 2 AKI in the cohort overall and 1.80 × (95 CI 1.26-2.57) among those with Child C cirrhosis, respectively. Similarly, NSBB use was associated with 1.30 × (95 CI 1.07-1.59) and 1.45 × (95 CI 1.03-2.03) the hazard of WLM, overall and in Child C, respectively. NSBB use was not significantly associated with AKI nor WLM among those with Child A. NSBB use is associated with Stage 2 AKI and WLM in patients awaiting liver transplantation and Child C cirrhosis. These data suggest cautious use of NSBBs in patients in this population.

Impact of bacterial infections prior to liver transplantation on post-transplant outcomes in patients with cirrhosis

Bacterial infections are frequent in patients with cirrhosis and increase the risk of death and drop-out from liver transplant (LT) waiting list. In patients with bacterial infections, LT is frequently delayed because of the fear of poor outcomes. We evaluated the impact of pre-LT infections on post-LT complications and survival. From 2012 to 2018, consecutive patients transplanted at the Hospital of Padua were identified and classified in two groups: patients surviving an episode of bacterial infection within 3 months before LT (study group) and patients without infections before LT (control group). Post-LT outcomes (complications, new infections, survival) were collected. A total of 466 LT recipients were identified (study group n= 108; control group n= 358). After LT, the study group had a higher incidence of new bacterial (57% vs. 20%, p <0.001) and fungal infections (14% vs. 5%, p= 0.001) and of septic shock (8% vs. 2%, p= 0.004) than the control group. Along with the model for end-stage liver disease (MELD) score and alcohol-related cirrhosis, bacterial infection pre-LT was an independent predictor of post-LT infections (odds ratio= 3.92; p <0.001). Nevertheless, no significant difference was found in 1-year (88% vs. 89%, p= 0.579) and 5-year survival rates (76% vs. 75%, p= 0.829) between the study group and control group. Within the study group, no association was found between the time elapsed from infection improvement/resolution to LT and post-LT outcomes. Patients with pre-LT infections have a higher risk of new bacterial and fungal infections and of septic shock after LT. However, post-LT survival is excellent. Therefore, as soon as the bacterial infection is improving/resolving, transplant should not be delayed, but patients with pre-transplant bacterial infections require active surveillance for infections after LT. Bacterial infections increase mortality and delay transplant in patients with cirrhosis awaiting liver transplantation (LT). Little is known about the impact of adequately treated infections before LT on post-transplant complications and outcomes. The study highlights that pre-LT infections increase the risk of post-LT infections, but post-LT survival rates are excellent despite the risk. These findings suggest that physicians should not delay LT because of concerns about pre-LT infections, but instead should actively monitor these patients for infections after surgery.

Nutritional optimization in liver transplant patients: from the pre-transplant setting to post-transplant outcome.

malnutrition and its clinical phenotypes, sarcopenia, and frailty, are prevalent conditions that affect patients with cirrhosis awaiting liver transplantation. The link between malnutrition, sarcopenia, and frailty and a higher risk of complications or death (before and after liver transplantation) is well established. Accordingly, the optimization of nutritional status could optimize both access to liver transplantation and the outcome following the surgery. Whether optimization of nutritional status in patients awaiting LT is associated with improved outcomes after transplant is the focus of this review. This includes the use of specialized regimens such as immune-enhancing or branchedchain amino-acids-enhanced diets. we discuss here the results of the few available studies in the field and provide an expert opinion of the obstacles that have led, so far, to an absence of benefit of such specialized regimens as compared to standard nutritional support. In the next future, combining nutritional optimization with exercise and enhanced recovery after surgery (ERAS) protocols could help optimize outcomes following liver transplantation.

Global Leadership Initiative on Malnutrition criteria for the diagnosis of malnutrition and prediction of mortality in patients awaiting liver transplant: A validation study

ObjectivesThe Global Leadership Initiative on Malnutrition (GLIM) is a framework aiming to standardize malnutrition diagnosis. However, it still needs to be validated, in particular for patients with chronic liver disease. This study aimed to validate the GLIM criteria in patients with liver cirrhosis awaiting liver transplant (LTx). MethodsThis was a retrospective observational study carried out with adult patients on the waiting list for LTx, consecutively evaluated between 2006 and 2021. The phenotypic criteria were unintentional weight loss, low body mass index, and reduced muscle mass (midarm muscle circumference [MAMC]). The etiologic criteria were high Model for End-Stage Liver Disease (MELD) and MELD adjusted for serum sodium (MELD-Na) scores, the Child–Pugh score, low serum albumin, and low food intake and/or assimilation. Forty-three GLIM combinations were tested. Sensitivity (SE), specificity (SP), positive and negative predictive values, and machine learning (ML) techniques were used. Survival analysis with Cox regression was carried out. ResultsA total of 419 patients with advanced liver cirrhosis were included (median age, 52.0 y [46–59 y]; 69.2% male; 68.8% malnourished according to the Subjective Global Assessment [SGA]). The prevalence of malnutrition by the GLIM criteria ranged from 3.1% to 58.2%, and five combinations had SE or SP >80%. The MAMC as a phenotypic criterion with MELD and MELD-Na as etiologic criteria were predictors of mortality. The MAMC and the presence of any phenotypic criteria associated with liver disease parameters and low food intake or assimilation were associated with malnutrition prediction in ML analysis. ConclusionsThe MAMC and liver disease parameters were associated with malnutrition diagnosis by SGA and were also predictors of 1-y mortality in patients with liver cirrhosis awaiting LTx.

Serum and plasma protein biomarkers associated with frailty in patients with cirrhosis.

Frailty, a clinical phenotype of decreased physiological reserve, is a strong determinant of adverse health outcomes in patients with cirrhosis. The only cirrhosis-specific frailty metric is the Liver Frailty Index (LFI), which must be administered in person and may not be feasible for every clinical scenario. We sought to discover candidate serum/plasma protein biomarkers that could differentiate frail from robust patients with cirrhosis. A total of 140 adults with cirrhosis awaiting liver transplantation in the ambulatory setting with LFI assessments and available serum/plasma samples were included. We selected 70 pairs of patients on opposite ends of the frailty spectrum (LFI>4.4 for frail and LFI<3.2 for robust) who were matched by age, sex, etiology, HCC, and Model for End-Stage Liver Disease-Sodium. Twenty-five biomarkers with biologically plausible associations with frailty were analyzed using ELISA by a single laboratory. Conditional logistic regression was used to examine their association with frailty. Of the 25 biomarkers analyzed, we identified 7 proteins that were differentially expressed between frail and robust patients. We observed differences in 6 of the 7 proteins in the expected direction: (a) higher median values in frail versus robust with growth differentiation factor-15 (3682 vs. 2249pg/mL), IL-6 (17.4 vs. 6.4pg/mL), TNF-alpha receptor 1 (2062 vs. 1627pg/mL), leucine-rich alpha-2 glycoprotein (44.0 vs. 38.6μg/mL), and myostatin (4066 vs. 6006ng/mL) and (b) lower median values in frail versus robust with alpha-2-Heremans-Schmid glycoprotein (0.11 vs. 0.13mg/mL) and free total testosterone (1.2 vs. 2.4ng/mL). These biomarkers represent inflammatory, musculoskeletal, and endocrine/metabolic systems, reflecting the multiple physiological derangements observed in frailty. These data lay the foundation for confirmatory work and development of a laboratory frailty index for patients with cirrhosis to improve diagnosis and prognostication.

Validation of MELD 3.0 scoring system in East Asian patients with cirrhosis awaiting liver transplantation.

Recently, a new predictive model that jointly considers the Model of End-stage Liver Disease (MELD) 3.0 and albumin has been proposed. This study investigated the performance of the MELD 3.0 score in predicting the 3-month survival of East Asian patients with cirrhosis compared with the other MELD-based scores. Validation was performed with the retrospective data of 2153 patients in South Korea who were listed for liver transplantation (LT). Discrimination and calibration analyses were performed using the MELD-based scores as an independent variable. On average, patients had the original MELD score of 18.70 ± 9.65. Alcohol (39.99%) and chronic HBV (38.55%) were the 2 main etiologies. The MELD 3.0 with albumin showed slightly better discrimination [c-index = 0.738, incremental AUC (iAUC) = 0.719] compared with the MELD 3.0 without albumin (c-index = 0.737, iAUC = 0.715), MELD-Na (c-index = 0.730, iAUC = 0.707), or the original MELD (c-index = 0.718, iAUC = 0.687) for predicting 3-month survival but not significantly different compared with prior models. Likewise, in the stratified analysis according to the strata of MELD, although the performance of MELD 3.0 was better throughout all the MELD strata than MELD original, there was no statistical difference in performance. The MELD 3.0 with albumin reclassified 22.61% of cases classified by the original MELD to higher MELD score categories, and there was no significant difference in the reclassification rate between males and females. The predictive power of the MELD-based system is lower in Asian populations than in western countries. Nonetheless, the MELD 3.0 score with albumin was significantly better in predicting the short-term prognosis of East Asian patients on the LT waitlist than the current allocation system, original MELD.

CT-quantified sarcopenic visceral obesity is associated with poor transplant waitlist mortality in patients with cirrhosis.

Sarcopenic obesity is associated with higher rates of morbidity and mortality than seen with either sarcopenia or obesity alone. We aimed to define sarcopenic visceral obesity (SVO) using CT-quantified skeletal muscle index and visceral-to-subcutaneous adipose tissue ratio and to examine its association with waitlist mortality in patients with cirrhosis. Included were 326 adults with cirrhosis awaiting liver transplantation in the ambulatory setting with available abdominal CT within 6 months from enrollment between February 2015 and January 2018. SVO was defined as patients with sarcopenia (skeletal muscle index <50cm 2 /m 2 in men and <39cm 2 /m 2 in women) and visceral obesity (visceral-to-subcutaneous adipose tissue ratio ≥1.21 in men and ≥0.48 in women). The percentage who met criteria for sarcopenia, visceral obesity, and SVO were 44%, 29%, and 13%, respectively. Cumulative incidence of waitlist mortality was higher in patients with SVO compared to patients with sarcopenia without visceral obesity or visceral obesity without sarcopenia at 12 months (40% vs. 21% vs. 12%) (overall logrank p =0.003). In univariable Cox regression, SVO was associated with waitlist mortality (HR: 3.42, 95% CI: 1.58-7.39), which remained significant after adjusting for age, sex, diabetes, ascites, encephalopathy, MELDNa, liver frailty index, and different body compositions (HR: 2.64, 95% CI: 1.11-6.30). SVO was associated with increase waitlist mortality in patients with cirrhosis in the ambulatory setting awaiting liver transplantation. Concurrent loss of skeletal muscle and gain of adipose tissue seen in SVO quantified by CT may be a useful and objective measurement to identify patients at risk for suboptimal pretransplant outcomes.

Implicit bias and the gender inequity in liver transplantation

Women with cirrhosis awaiting liver transplantation are less likely to receive a transplant and more likely to die than men. While differences in body size and estimation of kidney function are well-studied contributors to this gender inequity, what has received relatively little mention as a potential contributing factor is the possibility of implicit bias. Implicit bias is defined as "any unconscious or unacknowledged preference that affects a person's outlook or behavior." The undeniable presence of implicit bias, a factor that is known to negatively influence health outcomes for women, within our health care system means that patients interacting within our transplant system may still experience unequal treatment despite our best efforts to modify the allocation system at the national level. Awareness of this additional source of gender-based disparities is the first step. In this article, we posit that implicit bias in liver transplantation may exacerbate the gender inequity in transplant access and provide examples in the literature to support this assertion. Lastly, we offer strategies that could be applied at the individual or the healthcare delivery system levels to help reduce the influence of implicit bias on the gender inequity in liver transplantation.

Impact of Cirrhotic Cardiomyopathy Diagnosed According to Different Criteria on Patients with Cirrhosis Awaiting Liver Transplantation: A Retrospective Cohort Study.

Recently, the Cirrhotic Cardiomyopathy Consortium (Consortium) proposed criteria to replace the World Congress of Gastroenterology (WGO) criteria for cirrhotic cardiomyopathy (CCM) using contemporary echocardiography parameters. We assessed the impact of substituting WGO by Consortium criteria on the frequency of diagnosis and clinical outcomes in patients with cirrhosis awaiting liver transplantation (LT). Consecutive adults with cirrhosis approved for LT with echocardiography evaluation from January 2014 to December 2016 were screened. Patients with structural heart diseases were excluded. Two primary outcomes were: (1) frequency of CCM; (2) association of CCM with pre-transplant mortality. The secondary outcomes were pre-LT complications of acute kidney injury (AKI) and/or hepatic encephalopathy (HE), and post-LT mortality. Of 386 patients screened, 278 were included. 238 (85.6%) and 208 (74.8%) patients met Consortium and WGO criteria, respectively; 180 (64.7%) patients fulfilled both the criteria, while 12 (4.3%) patients had no evidence of CCM by either criterion. Pre-LT mortality rates in Consortium-CCM group were similar to the other groups (19.3% vs 20.2% vs 25.0%). The patients with advanced diastolic dysfunction (DD) per Consortium-CCM criteria had higher mortality than the other groups. The rates of pre-LT AKI/HE rates and post-LT mortality were similar in Consortium-CCM and WGO-CCM groups. The Consortium criteria do not impact the prevalence of CCM compared to WGO criteria and have similar predictive accuracy. Presence of advanced DD per the Consortium criteria increases the risk of pre-LT mortality and complications of AKI/HE. The patients with advanced DD could benefit from further monitoring and treatment.

Frailty, mortality, and health care utilization after liver transplantation: From the Multicenter Functional Assessment in Liver Transplantation (FrAILT) Study.

Frailty is a well-established risk factor for poor outcomes in patients with cirrhosis awaiting liver transplantation (LT), but whether it predicts outcomes among those who have undergone LT is unknown. Adult LT recipients from 8 US centers (2012-2019) were included. Pre-LT frailty was assessed in the ambulatory setting using the Liver Frailty Index (LFI). "Frail" was defined by an optimal cut point of LFI ≥ 4.5. We used the 75th percentile to define "prolonged" post-LT length of stay (LOS; ≥12days), intensive care unit (ICU) days (≥4days), and inpatient days within 90 post-LT days (≥17days). Of 1166 LT recipients, 21% were frail pre-LT. Cumulative incidence of death at 1 and 5years was 6% and 16% for frail and 4% and 10% for nonfrail patients (overall log-rank p=0.02). Pre-LT frailty was associated with an unadjusted 62% increased risk of post-LT mortality (95% CI, 1.08-2.44); after adjustment for body mass index, HCC, donor age, and donation after cardiac death status, the HR was 2.13 (95% CI, 1.39-3.26). Patients who were frail versus nonfrail experienced a higher adjusted odds of prolonged LT LOS (OR, 2.00; 95% CI, 1.47-2.73), ICU stay (OR, 1.56; 95% CI, 1.12-2.14), inpatient days within 90 post-LT days (OR, 1.72; 95% CI, 1.25-2.37), and nonhome discharge (OR, 2.50; 95% CI, 1.58-3.97). Compared with nonfrail patients, frail LT recipients had a higher risk of post-LT death and greater post-LT health care utilization, although overall post-LT survival was acceptable. These data lay the foundation to investigate whether targeting pre-LT frailty will improve post-LT outcomes and reduce resource utilization.

Malnutrition, Frailty, and Sarcopenia in Patients With Cirrhosis: 2021 Practice Guidance by the American Association for the Study of Liver Diseases.

Malnutrition, Frailty, and Sarcopenia in Patients With Cirrhosis: 2021 Practice Guidance by the American Association for the Study of Liver Diseases.

Treatment of refractory ascites with an automated low flow ascites pump in patients awaiting liver transplantation

BackgroundFor patients with liver cirrhosis awaiting liver transplantation who suffer from refractory ascites (RA), standard treatment consists of repeated large volume paracentesis. The automated low-flow ascites-pump (alfapump) offers an innovative treatment alternative for patients with RA, if TIPSS is contraindicated or ineffective. This study addresses the feasibility of alfapump treatment in patients awaiting liver transplantation. MethodsBetween 2012 and 2018, patients listed for liver transplantation who were treated with an alfapump were included in this retrospective single centre study. ResultsOf 22 patients listed for liver transplantation and treated with an alfapump, 14 were finally transplanted. Alcohol-related liver disease was the most common aetiology for liver cirrhosis (n = 11), followed by hepatitis C, hepatitis B and NASH. Mean age at listing was 56.3 years and 68.2% of patients were male. The average daily ascites volume pumped by the device was 1076 ml. During transplant surgery, no alfapump-related complications occurred. The alfapump was removed at the end of the transplant procedure in eight patients and left in place in three patients for up to 104 days, whereas three patients had the pump removed prior to the transplantation. Overall survival was significantly better in patients that were finally transplanted (log-rank p < 0.0001). Five patients (22.7%) required at least one alfapump-related re-intervention. ConclusionTreatment with an alfapump in patients on the liver transplant waiting list with refractory ascites is feasible. The alfapump did not affect the transplant procedure and was explanted in most patients at the end of the transplant surgery.

Is antivitamin K reversal required in patients with cirrhosis undergoing liver transplantation?

Antivitamin K agent (AVK) reversal in patients with cirrhosis awaiting liver transplantation (LT) is not defined in guidelines. We investigated the effect of reversion with prothrombin complex concentrate (PCC) on intraoperative transfusion, bleeding, and safety in LT patients on AVK. In 511 patients undergoing LT, we identified 25 patients treated with AVK (AVK group) and 13 patients with incidental portal vein thrombosis (PVT) without AVK (incidental PVT group). Fifty patients who underwent LT without PVT or AVK matched by age, model for end stage of liver disease (MELD), body mass index (BMI), and cirrhosis etiology were selected as the control group. There were no significant differences between the three groups in intraoperative blood loss, transfusion, and postoperative bleeding. In the AVK group, there were no differences between patients who received PCC and those who did not in intraoperative blood loss, red blood cells, fibrinogen, and platelet transfusion, or postoperative bleeding. PCC use had no effect on RBC transfusion in patients who had international normalized ratio or clotting time above versus below median values of the two parameters at baseline (2.3 and 103 s, respectively). No thrombotic events were detected in patients who received PCC. These data suggest that systematic administration of PCC to revert AVK prior to LT should be reconsidered.

Efficacy and Safety of Endoscopic Balloon Placement for Weight Loss in Patients With Cirrhosis Awaiting Liver Transplantation.

The efficacy and safety of a fluid-filled intragastric balloon (IGB) for weight loss in patients with cirrhosis on the liver transplantation (LT) waiting list is unknown. We enrolled stable compensated patients with body mass index >35 kg/m2 and on the waiting list for IGB placement endoscopically for a maximum of 6months. A total of 8 patients (7 men) aged mean ± SD, 56 ± 4.6 years with Model for End-Stage Liver Disease-sodium (MELD-Na) scores 14.1±3.4 experienced weight reduction (146±22.2 kg versus 127±21.6kg [P=0.005] with IGB in place and 130±24.6kg [P=0.014] at 6months), with a total body weight loss of 12.2%±8.8% with IGBs in place and 10.9%±8.9% at 6months. Body fat decreased from 48.6%±5.8% to 40.6%±6.4% (P=0.001) and lean mass increased from 51.3%±6% to 59.4%±6.4% (P=0.001). No change in MELD-Na scores occurred (P=0.770). Early balloon retrieval was attributed to accommodative symptoms (n=2) and liver decompensation (n=1). Mallory Weiss tears (n=3), but no portal hypertensive bleeding, occurred. Liver decompensation and/or hepatocellular carcinoma (HCC) developed in 3 patients. A total of 4 patients with LT ± sleeve gastrectomy maintained overall weight loss. Of 4 patients who did not receive transplants, 2 experienced weight regain. IGB results in short-term weight loss in patients with cirrhosis awaiting LT, with body fat loss without lean mass loss. Adverse effects were common. Decompensation and HCC did occur, with uncertainty of the relation to weight loss, and thus careful patient selection and close follow-up are required.

Expert consensus on the use of human serum albumin in critically ill patients.

Expert consensus on the use of human serum albumin in critically ill patients.

Association of Frailty and Sex With Wait List Mortality in Liver Transplant Candidates in the Multicenter Functional Assessment in Liver Transplantation (FrAILT) Study

Female liver transplant candidates experience higher rates of wait list mortality than male candidates. Frailty is a critical determinant of mortality in patients with cirrhosis, but how frailty differs between women and men is unknown. To determine whether frailty is associated with the gap between women and men in mortality among patients with cirrhosis awaiting liver transplantation. This prospective cohort study enrolled 1405 adults with cirrhosis awaiting liver transplant without hepatocellular carcinoma seen during 3436 ambulatory clinic visits at 9 US liver transplant centers. Data were collected from January 1, 2012, to October 1, 2019, and analyzed from August 30, 2019, to October 30, 2020. At outpatient evaluation, the Liver Frailty Index (LFI) score was calculated (grip strength, chair stands, and balance). The risk of wait list mortality was quantified using Cox proportional hazards regression by frailty. Mediation analysis was used to quantify the contribution of frailty to the gap in wait list mortality between women and men. Of 1405 participants, 578 (41%) were women and 827 (59%) were men (median age, 58 [interquartile range (IQR), 50-63] years). Women and men had similar median scores on the laboratory-based Model for End-stage Liver Disease incorporating sodium levels (MELDNa) (women, 18 [IQR, 14-23]; men, 18 [IQR, 15-22]), but baseline LFI was higher in women (mean [SD], 4.12 [0.85] vs 4.00 [0.82]; P = .005). Women displayed worse balance of less than 30 seconds (145 [25%] vs 149 [18%]; P = .003), worse sex-adjusted grip (mean [SD], -0.31 [1.08] vs -0.16 [1.08] kg; P = .01), and fewer chair stands per second (median, 0.35 [IQR, 0.23-0.46] vs 0.37 [IQR, 0.25-0.49]; P = .04). In unadjusted mixed-effects models, LFI was 0.15 (95% CI, 0.06-0.23) units higher in women than men (P = .001). After adjustment for other variables associated with frailty, LFI was 0.16 (95% CI, 0.08-0.23) units higher in women than men (P < .001). In unadjusted regression, women experienced a 34% (95% CI, 3%-74%) increased risk of wait list mortality than men (P = .03). Sequential covariable adjustment did not alter the association between sex and wait list mortality; however, adjustment for LFI attenuated the mortality gap between women and men. In mediation analysis, an estimated 13.0% (IQR, 0.5%-132.0%) of the gender gap in wait list mortality was mediated by frailty. These findings demonstrate that women with cirrhosis display worse frailty scores than men despite similar MELDNa scores. The higher risk of wait list mortality that women experienced appeared to be explained in part by frailty.