Expedited liver transplantation as first-line therapy for severe alcohol hepatitis: ELFSAH; deferring corticosteroids in the sickest subset of patients.

BACKGROUND & AIMS: Severe alcohol-associated hepatitis (SAH) represents a lethal subset of alcohol-associated liver disease. Although corticosteroids are recommended by guidelines, their efficacy and safety remain questionable and so liver transplantation (LT) has been increasingly utilized. The timing and indication of corticosteroid use, specifically in patients being considered for LT requires further clarification. METHODS: A retrospective analysis was conducted on 256 patients with SAH between 2018 and 2022 at a single US center. RESULTS: Twenty of these patients underwent LT. Of the 256 patients, 38% had what we termed "catastrophic" SAH, defined as a MELD-Na ≥35 and/or discriminant function (DF) ≥100, which carried a mortality of 90% without LT. Compared with 100 matched controls, patients undergoing LT exhibited a one-year survival rate of 100% versus 35% (p < .0005). LT provided an absolute risk reduction of 65%, with a number needed to treat of 1.5. Steroid utilization in the entire cohort was 19% with 60% developing severe complications. Patients administered steroids were younger with lower MELD and DF scores. Only 10% of those prescribed steroids derived a favorable response. Sustained alcohol use post-LT was 20%. CONCLUSIONS: We propose ELFSAH: Expedited LT as First Line Therapy for SAH; challenging the current paradigm with recommendations to defer steroids in patients with "catastrophic" SAH (defined as: MELD-Na ≥35 and/or DF ≥100). Patients should be seen urgently by hepatology, transplant surgery, psychiatry and social work. Patients without an absolute contraindication should be referred for LT as first-line therapy during their index admission.

TEG-based transfusion protocol is associated with decreased blood product use without increased risk of hemoperitoneum.

BACKGROUND: Thromboelastography (TEG) informs the need for blood product transfusions to prevent procedural bleeding complications in patients with cirrhosis. We aimed to evaluate the impact of using a TEG-based transfusion protocol on blood product utilization before paracentesis and the post-paracentesis hemoperitoneum (PPH) incidence. METHODS: We conducted an ambispective analysis of patients with cirrhosis who underwent paracentesis from 2017 to 2021. In May 2019, we enacted a TEG-based transfusion protocol to guide pre-paracentesis blood product use. Patients with platelets < 20,000 or international normalized ratio ≥ 4 underwent TEG and received blood products if r value > 10 min or MA <30 mm. Patients were divided into pre-TEG and post-TEG protocol cohorts based on the date of paracentesis. Pre-paracentesis blood product transfusions in the form of platelets, fresh frozen plasma, and cryoprecipitates were recorded. PPH was defined as a decrease in hemoglobin of ≥1 g and the presence of blood on diagnostic imaging and/or the need for therapeutic intervention. RESULTS: A total of 483 patients underwent 1281 paracenteses. The main etiologies of cirrhosis were alcohol (43%) and NASH (25%), and the mean MELD-sodium was 22±6. Pre-TEG and post-TEG protocol cohort sizes were similar: 253 patients and 607 paracenteses versus 230 patients and 674 paracenteses. After TEG-protocol implementation, blood product transfusions decreased significantly (228 vs. 49 products, p<0.001) with associated cost savings. One patient in each cohort developed PPH. CONCLUSION: Implementation of a pre-paracentesis TEG-based transfusion protocol for patients with cirrhosis successfully resulted in decreased blood product use with no associated increase in incidence of PPH.

Low Daily Step Count Is Associated With a High Risk of Hospital Admission and Death in Community-Dwelling Patients With Cirrhosis.

BACKGROUND & AIMS: Daily step count measures cardiorespiratory fitness and has been associated with clinical outcomes. However, its utility in patients with cirrhosis remains largely unexplored. We aimed to investigate the association between step count, frailty metrics, and clinical outcomes in cirrhosis. METHODS: All participants underwent frailty evaluation with the liver frailty index, 6-minute walk test, and gait speed test. To monitor step count, participants were given a personal activity tracker (PAT). A subset also was invited to use Exercise and Liver FITness (EL-FIT). Daily step counts from the first week of PAT use and frailty metrics were investigated as predictors of hospital admission and mortality. RESULTS: There were 116 patients included (age, 56 ± 11 y; male, 55%; body mass index, 31 ± 7; model for end-stage liver disease-sodium, 15 ± 7). The main etiologies of cirrhosis were alcohol-related (33%) and nonalcoholic steatohepatitis (30%). Monitoring for the week was accomplished in 80% of participants given both PAT+EL-FIT vs 62% in those with PAT only (P = .04). During follow-up evaluation, hospital admission was observed in 55% and death in 15%. Kaplan-Meir curves showed increased readmission and deaths among patients performing in the lowest quartile (ie, <1200 steps/d). When adjusted by model for end-stage liver disease-sodium and EL-FIT use, the lowest quartile was associated with hospital admission and death (hazard ratio, HR [95% confidence interval], 1.90 [1.09-3.30] and 3.46 [1.23-9.68], respectively), along with the 6-minute walk test (HR, 0.63 [0.47-0.83] and 0.66 [0.44-0.99] per 100 m, respectively) and gait speed test (HR, 0.29 [0.11-0.72] and 0.21 [0.05-0.84], respectively). CONCLUSIONS: Daily step count predicted hospital admission and mortality rates in patients with cirrhosis, similar to the current standard frailty metrics. Incorporation of a physical training-dedicated smartphone application was associated with increased PAT use and step reporting.

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.

Office-Based Weight Loss Counseling Is Ineffective in Liver Transplant Recipients.

BACKGROUND: Weight gain after liver transplantation (LT) is a predictor of major morbidity and mortality post-LT; however, there are no data regarding weight loss following LT. The current study evaluates the effectiveness of standard lifestyle intervention in LT recipients. METHODS: All adult LT recipients with body mass index (BMI) ≥ 25 kg/m2 who followed up in post-LT clinic from January 2013 to January 2016 were given standard lifestyle advice based on societal recommendations which was reinforced at 24 weeks. Patients were followed for a total of 48 weeks to assess the impact of such advice on weight. Primary outcome was achieving weight loss ≥ 5% of the body weight after 48 weeks of follow-up. RESULTS: A total of 151 patients with 86 (56.0%) overweight and 65 (44.0%) obese patients were enrolled in the study. The mean BMI at baseline increased from 30.2 ± 3.7 to 30.9 ± 4.3 kg/m2 at 48-week follow-up (p = 0.001). Over the course of study, 58 (38.4%) patients lost any weight and weight loss greater than 5% and 10% occurred in only 18 (11.9%) and 8 (5.3%) of the entire cohort, respectively. Higher level of education was associated with increased likelihood of weight loss (OR 9.8, 95% CI 2.6, 36.9, p = 0.001), while nonalcoholic steatohepatitis as etiology of liver disease (HR 3.7, 95% CI 1.4, 9.7, p = 0.007) was associated with weight gain. CONCLUSION: The practice of office-based lifestyle intervention is ineffective in achieving clinically significant weight loss in LT recipients, and additional strategies are required to mitigate post-LT weight gain.

The Impact of Coronary Artery Disease and Statins on Survival After Liver Transplantation.

Cardiovascular disease (CVD) is a major contributor to longterm mortality after liver transplantation (LT) necessitating aggressive modification of CVD risk. However, it is unclear how coronary artery disease (CAD) and the development of dyslipidemia following LT impacts clinical outcomes and how management of these factors may impact survival. Patients undergoing LT at Virginia Commonwealth University from January 2007 to January 2017 were included (n = 495). CAD and risk factors in all potential liver transplantation recipients (LTRs) over the age of 50 years were evaluated via coronary angiography. The impact of pre-LT CAD after transplantation was evaluated via a survival analysis. Additionally, factors associated with new-onset dyslipidemia, statin use, and mortality were assessed using multiple logistic regression or Cox proportional hazards models. The mean age of the cohort was 55.3 ± 9.3 years at the time of LT, and median follow-up was 4.5 years. CAD was noted in 129 (26.1%) patients during the pre-LT evaluation. The presence or severity of pre-LT CAD did not impact post-LT survival. Dyslipidemia was present in 96 patients at LT, and 157 patients developed new-onset dyslipidemia after LT. Statins were underused as only 45.7% of patients with known CAD were on therapy. In patients with new-onset dyslipidemia, statin therapy was initiated in 111 (71.1%), and median time to initiation of statin therapy was 2.5 years. Statin use conferred survival benefit (hazard ratio, 0.25; 95% confidence interval, 0.12-0.49) and was well tolerated with only 12% of patients developing an adverse event requiring the cessation of therapy. In conclusion, pre-LT CAD did not impact survival after LT, potentially suggesting a role of accelerated atherosclerosis that may not be captured on pre-LT testing. Although statin therapy confers survival benefit, it is underused in LTRs.

The relationship between coronary artery disease and cardiovascular events early after liver transplantation.

BACKGROUND & AIMS: Cardiovascular complications are major contributors to mortality at liver transplantation (LT). However, the impact of coronary artery disease (CAD) on these complications is not well-understood as the literature is limited by non-invasive assessment of CAD, which is suboptimal in patients with cirrhosis. Thus, the current study evaluated cardiovascular events at LT stratified according to the presence and severity of CAD quantified on coronary angiography. METHODS: All patients who had LT from January 2010 to January 2017 were evaluated (N = 348), but analysis was restricted to patients who had coronary angiography prior to LT (N = 283). Protocol coronary angiography was performed in all patients' ages >50 years, history of CAD, abnormal cardiac stress test or risk factors for CAD. The primary outcome was a cardiovascular composite outcome including myocardial infraction (MI), cardiac arrest, stroke, cardiac death, heart failure or arrhythmia occurring within 4 weeks after LT. RESULTS: CAD was present in 92(32.5%) patients and 32(11.3%) had obstructive CAD. During the study period, 72(25.4%) patients met the primary cardiovascular outcome, the most common being arrhythmia (N = 59 or 20.8%). Non-ST elevation MI occurred in 11(3.9%) of patients. A total of 10 deaths (3.5%) occurred, of which 6(2.1%) were attributable to cardiac death. There was no evidence of a relationship between the presence and severity of CAD and composite cardiovascular events. In multiple regression modelling, only diabetes [OR 2.62, 95%CI (1.49, 4.64), P < 0.001] was associated with the likelihood of having a cardiovascular event. CONCLUSION: Cardiovascular disease mortality is the most important contributor of early mortality after LT but is not related to the severity of CAD.

Utilization of aspirin and statin in management of coronary artery disease in patients with cirrhosis undergoing liver transplant evaluation.

Coronary artery disease (CAD) assessment is a vital part of liver transplantation (LT) evaluation, as it allows for identification and medical optimization prior to transplantation. Although aspirin and statins are standard of care for CAD, they are not universally used in cirrhosis due to concerns about adverse events. Per protocol, coronary angiography was performed as part of the LT evaluation in all patients over the age of 50 years or with CAD risk factors, even if they were younger than 50. Optimal CAD medical management was defined as the use of both statin and aspirin, unless a contraindication was documented. Impact of these medications on hepatic decompensation, renal function, gastrointestinal bleeding, and need for transfusion was evaluated. CAD was detected in 84/228 (36.8%) patients. Lipid profile was similar in patients with and without CAD. In patients with CAD, statins were started in 19 (23%), while aspirin was used in 30 (36%) patients. In patients with obstructive or multivessel CAD, statin therapy was used only in 41% and 65%, respectively. Statins were more likely to be prescribed in patients with diabetes (32% versus 15%, P = 0.05) and history of dyslipidemia (38% versus 15%, P = 0.02). Use of statin therapy was not linked to hepatic decompensation, hospitalization, or rise in Model for End-Stage Liver Disease (MELD). Similarly, use of aspirin therapy was not associated with increased risk acute variceal hemorrhage, gastrointestinal bleeding, or worsening anemia. In conclusion, in decompensated cirrhosis, lipid profile alone is unable to risk stratify patients with CAD. Statin and aspirin appear to be safe. However, they are significantly underutilized for the management of CAD in this patient population. Liver Transplantation 24 872-880 2018 AASLD.