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.

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.

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.

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. ated (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. K E Y W O R D S cardiovascular events, cirrhosis, coronary artery disease, liver transplantation 1364 | PATEL ET AL. | INTRODUC TI ONCardiovascular disease (CVD) is an important contributor to morbidity and mortality during and immediately after liver transplantation (LT). 1,2 More importantly, the presence and severity of coronary artery disease (CAD) has been linked to worse outcomes at LT. 2 The gold standard for CAD assessment is coronary angiography, but it is often deferred in many patients with decompensated cirrhosis because of perceived higher risk of complications, thereby introducing a selection bias in the published literature. [3][4][5] This is compounded further by the suboptimal diagnostic performance of non-invasive cardiac testing in patients with cirrhosis because of blunted heart rate response, body habitus, oedema, deconditioning and impaired functional status. [6][7][8] Thus, it is difficult to interpret the findings of the published literature that have evaluated the impact of underlying CAD on CVD events at the time of LT that used non-invasive cardiac assessment. 9,10 Using coronary angiography, a recent study demonstrated higher prevalence of CAD in potential LT waitlist registrants compared to the general population; 11,12 however, because of relatively small sample size, the association between CAD a...

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/m 2 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/m 2 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. ConclusionThe 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.