Brain Integrity Changes underlying Cognitive and Functional Recovery Postliver Transplant Continue to Evolve Over 1 Year

Abstract: Background There is evidence of brain recovery on brain MRI early postliver transplant(LT) but the longer-term impact is unclear. Aim of this study was to determine the change in brain MRI parameters, cognition and health-related quality of life (HRQOL) between 6 and 12 months post-LT. Methods Listed cirrhotics underwent cognitive, HRQOL and brain MRI pre, 6 months (post-LT1) and 1-year (post-LT2) post-LT. Assessment of MRI changes between visits was performed for ammonia-associated metabolite changes using spectroscopy (MRS), white matter changes using Tract-based Spatial Statistics (TBSS) analysis on Diffusion Tensor Imaging (DTI) data and grey matter changes using Voxel-based morphometry (VBM) analysis on 3D high resolution T1-weighted images. Results Forty-five patients were included of which, twenty-three were tested at all visits. Cognitive and HRQOL scores improved between all visits compared to pre-LT values. This trend continued on MRS with reduced glutamine+glutamate(Glx) and higher myoinositol(mI), Choline(Cho) between pre-LT/post-LT1 but lower degrees of improvement between post-LT1/post-LT2. On DTI, mean-diffusivity(MD), linear-diffusivity(LD) and mode of anisotropy(MO) continued to increase in the posterior internal capsule at both post-LT visits. On VBM, a continued increase was seen in basal ganglia grey matter between both post-LT visits was seen. Conclusions HRQOL and cognition continue to improve compared to pre-LT values up to 1 year post-LT, although the rate of improvement slows down after 6 months. Grey matter increase is steady over time at 1 year although changes in ammonia-related metabolites and white matter integrity improve at a slower pace at 1 year post-LT. Corresponding Author: Jasmohan S Bajaj, MD, MS, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, 1201 Broad Rock Boulevard, Richmond, VA, 23221, USA, Phone: (804) 675-5802, Fax: (804) 675 5816. Email: jasmohan.bajaj@vcuhealth.org Author contributions: JSB, VA, JS, FGM, JBW were involved in research design, performance of the research and data analysis, MBW, HSG, DMH, MF, EAG, AF, RKS, RTS, PP, AJS, MSS, SM, VL were involved in performance of the research, LRT was involved in data analysis, All authors participated in the writing of the paper. Funding: Partly supported by NIH RO1DK089713 and VA Merit Review 1I0CX001076 to JSB Disclosure: The authors declare no conflicts of interest Presentation: Portions of this study were presented as an oral presentation at the EASL conference in Amsterdam 2017. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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