Outcomes of Exercise Interventions in Patients With Advanced Liver Disease: A Systematic Review of Randomized Clinical Trials.

INTRODUCTION: Frailty and sarcopenia are common complications of advanced liver disease. Owing to associated morbidity/mortality, there have been targeted efforts to prevent and/or improve both by enrolling these patients in focused exercise programs. This review systematically analyzes the data of randomized clinical trials (RCTs) on anthropometric, physical fitness, quality-of-life, and safety outcomes of exercise interventions in patients with advanced liver disease. METHODS: Two authors independently searched trials on PubMed and EMBASE from inception up to November 18, 2021. A third independent arbitrator adjudicated all disagreements. We qualitatively summarized these outcomes as follows: (i) muscular fitness (maximal inspiratory/expiratory pressures, muscle size, muscle strength, and bioimpedance testing), (ii) cardiorespiratory fitness (cardiopulmonary exercise testing and 6-minute walk distance), (iii) quality of life, and (iv) others (safety or frailty indices). RESULTS: There were 11 RCTs (4 home-based interventions) with 358 participants. Interventions ranged from 8 to 14 weeks and included cycling, walking, resistance exercises, balance and coordination training, and respiratory exercises. All described outcomes compared preintervention with postintervention measurements. Nine studies showed statistically significant improvements in at least 1 physical fitness variable. Ten studies showed statistically significant improvements in at least 1 muscular fitness variable. Six studies showed statistically significant improvements in at least 1 quality-of-life variable. Attrition rates ranged from 5% to 36%, and adherence rates ranged very widely from 14% to 100%. Only 1 study reported frailty indices. Notably, no complications of portal hypertension were seen in intervention groups in the 9 studies that reported these data. DISCUSSION: A review of 11 RCTs with 358 participants with advanced liver disease demonstrates that exercise interventions can have favorable outcomes on muscular/cardiorespiratory fitness and quality of life. Although attrition and adherence varied, these interventions seem to be safe in patients with cirrhosis and are well tolerated

Recipient IL28B polymorphism is an important independent predictor of posttransplant diabetes mellitus in liver transplant patients with chronic hepatitis C

IL28B polymorphisms are strongly associated with response to treatment for HCV infection. IL28B acts on interferon-stimulated genes via the JAK-STAT pathway, which has been implicated in development of insulin resistance. We investigated whether IL28B polymorphisms are associated with posttransplant diabetes mellitus (DM). Consecutive HCV patients who underwent liver transplantation between 1-1995 and 1-2011 were studied. Genotyping of the polymorphism rs12979860 was performed on DNA collected from donors and recipients. Posttransplant DM was screened for by fasting blood glucoses every 1-3 months. Of 221 included patients, 69 developed posttransplant DM (31%). Twenty-two patients with recipient IL28B genotype TT (48%), 25 with IL28B genotype CT (25%) and 22 with IL28B genotype CC (29%) developed posttransplant DM. TT genotype was statistically significantly associated with posttransplant DM over time (log rank p = 0.012 for TT vs. CT and p = 0.045 for TT vs. CC). Multivariate Cox regression analysis correcting for donor age, body mass index, baseline serum glucose, baseline serum cholesterol, recipient age and treated rejection, showed that recipient IL28B genotype TT was independently associated with posttransplant DM (hazard ratio 2.51; 95% confidence interval 1.17-5.40; p = 0.011). We conclude that the risk of developing posttransplant DM is significantly increased in recipients carrying the TT polymorphism of the IL28B gene. An analysis of liver transplant recipients with hepatitis C virus infection finds that the risk of developing posttransplant diabetes mellitus is significantly increased in recipients carrying the TT polymorphism of the IL28B gene

A North American Expert Opinion Statement on Sarcopenia in Liver Transplantation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151960/1/hep30828_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151960/2/hep30828.pd

Frailty in liver transplantation: An expert opinion statement from the American Society of Transplantation Liver and Intestinal Community of Practice

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149699/1/ajt15392_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149699/2/ajt15392.pd

A Day-4 Lille Model Predicts Response to Corticosteroids and Mortality in Severe Alcoholic Hepatitis

OBJECTIVES: Prednisolone therapy increases the risk of infections in patients with severe alcoholic hepatitis (SAH). We evaluated whether the use of the Lille Model at day 4 (LM4) is useful to predict response to prednisolone compared with the classic day 7 (LM7) in order to limit a futile exposure to corticosteroids. METHODS: We performed a retrospective analysis of a large multinational cohort of patients with SAH with Maddrey's discriminant function (DF) ≥32. Response to corticosteroids was assessed with LM4 and LM7, according to the validated cutoff value (CUV>0.45). Receiver operating characteristics (ROC) curves were constructed to determine the optimal CUV for LM4 and to compare accuracy between LM4, LM7, MELD (Model for End-Stage Liver Disease), and ABIC (age, bilirubin, international normalized ratio, and creatinine). Logistic regression models were constructed to predict 28- and 90-day mortality. Cox regression analysis was performed to assess long-term survival. RESULTS: A total of 163 (62.7%) out of 260 patients received corticosteroids. The median DF for the patients treated with corticosteroids was 64.1 (47.9-81.3). Overall 90-day mortality was 35.9%. The median LM4 and LM7 for the patients who received treatment was 0.39 (0.19-0.83) and 0.36 (0.13-0.77). LM4 was a strong independent predictor of 28-day mortality (OR 25.4, (95% confidence interval (CI) 5.1-126.8), P0.45, 28- and 90-day survival was significantly higher for responders (90% and 76%) than non-responders (66% and 40%), P<0.001. Importantly, the area under the ROC curve for predicting mortality for LM4 was similar than the classic LM7 (0.77 vs. 0.75, respectively: P=0.558). CONCLUSIONS: LM4 is as accurate as LM7 in predicting response to corticosteroids, as well as 28- and 90-day mortality. Assessing the efficacy of prednisolone at an earlier time point can avoid a more prolonged futile use of this therapy

Report from the American Society of Transplantation on frailty in solid organ transplantation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148387/1/ajt15198_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148387/2/ajt15198.pd

Measurement of associated W plus charm production in pp collisions at √s=7 TeV

Peer reviewe

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field