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

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

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

Peer reviewe

Physical Function, Physical Activity, and Quality of Life After Liver Transplantation

Robust physical activity after liver transplantation is an important determinant of longterm health, similar in its importance to the value of pretransplant activity for withstanding the immediate stress of transplantation. Although transplantation normally enables rapid recovery of liver synthetic and metabolic functions, the recovery of physical capacity and performance to normal levels is delayed and often incomplete. Anatomic measurements of sarcopenia and the physical performance indicators of frailty both tend to improve slowly, and they may, in fact, decrease further in the posttransplant period, especially when the common extrahepatic drivers of muscle loss, such as the elements of the metabolic syndrome, persist or intensify after transplantation. Posttransplant exercise improves fitness, which is a conclusion based on 2 observational studies and 3 randomized trials that assessed endpoints of strength testing, energy expenditure in metabolic equivalents, and peak or maximal oxygen uptake. Importantly, 1 controlled trial found that exercise also improved quality of life (QOL) measured by the Short Form 36 survey, consistent with multiple reports of the value of social support and engagement in sports activity for improving posttransplant QOL. Developing evidence-based standards for post-liver transplant physical activity baseline testing and sustainment of intensity and quality is a key unmet need in transplant hepatology. At present, it is reasonable for transplant teams to assess fitness and design a tailored exercise program when a recipient is first discharged, to record and reinforce progress at all posttransplant visits, and to set realistic longterm performance goals that will often achieve recommended standards for the healthy general population

A Telemedicine Alternative to the 6-Minute Walk Test Using Personal Activity Trackers in Liver Transplant Candidates

Background. The COVID-19 pandemic has limited liver transplant (LT) candidates access to clinics. Telehealth methods to assess frailty are needed. We developed a method to estimate the step length of LT candidates, which would permit remotely obtaining the 6-min walk test (6MWT) distance with a personal activity tracker (PAT). Methods. 6MWT was performed while candidates wore a PAT. On first 21 subjects (stride cohort), the step length was measured and compared with calculated one (6MWT-distance/6MWT steps). On a second cohort (PAT-6MWT; n = 116), we collected the 6MWT step count and used multivariable models to generate formulas estimating step length. We multiplied the estimated step length times 6MWT steps to estimate the distance and compared it to the measured distance. The liver frailty index (LFI) and 6MWT were used as frailty metrics. Results. Measured/calculated step length were highly correlated (ρ = 0.85; P < 0.001) in the stride cohort. In the PAT-6MWT cohort, LFI was the strongest variable associated with step length, along with height, albumin, and large-volume paracentesis (R2 = 0.58). On a second model without LFI, age, height, albumin, hemoglobin, and large-volume paracentesis were strongly associated with step length (R2 = 0.45). There was a robust correlation between observed 6MWT and PAT-6MWT utilizing step length equations with (ρ = 0.80; P < 0.001) or without LFI (ρ = 0.75; P < 0.001). Frailty by 6MWT <250 m did not change significantly using the observed (16%) or the with/without LFI-estimated (14%/12%) methods. Conclusions. We created a method to obtain 6MWT distance remotely with the use of a PAT. This novel approach opens the possibility of performing telemedicine PAT-6MWT to monitor LT candidates’ frailty status