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Liver transplantation significantly improves global functioning and cerebral processing.

ABSTRACT: The functional basis of cognitive and quality of life changes after liver transplant is unclear. We aimed to evaluate the neurometabolic and functional brain changes as modulators of cognition and quality of life after transplant in patients with cirrhosis who were with/without pretransplant cognitive impairment and hepatic encephalopathy (HE). Patients with cirrhosis underwent detailed cognitive and quality of life assessment at enrollment and 6 months after transplant. A subset underwent brain magnetic resonance imaging (functional magnetic resonance imaging [fMRI], diffusion tensor imaging [DTI], and magnetic resonance spectroscopy [MRS]) before and after transplant. Changes before and after transplant were analyzed in all patients and by dividing groups in those with/without pretransplant cognitive impairment or with/without pretransplant HE. MRS evaluated ammonia-related metabolites; fMRI studied brain activation for correct lure inhibition on the inhibitory control test; and DTI studied white matter integrity. Sixty-six patients (mean Model for End-Stage Liver Disease score, 21.8; 38 HE patients and 24 cognitively impaired [CI] patients) were enrolled. Quality of life was significantly worse in CI and HE groups before transplant, which improved to a lesser extent in those with prior cognitive impairment. In the entire group after transplant, there was (1) significantly lower brain activation needed for lure inhibition (shown on fMRI); (2) reversal of pretransplant ammonia-associated changes (shown on MRS); and (3) improved white matter integrity (shown on DTI). Importantly, study findings suggest that pretransplant cognitive impairment serves as a marker for clinical outcomes. Regardless of pretransplant history of HE, it was the pretransplant cognitive impairment that was predictive of both posttransplant cognitive and psychosocial outcomes. Therefore, when working with patients and their families, a clinician may rely on the pretransplant cognitive profile to develop expectations regarding posttransplant neurobehavioral recovery. We conclude that functional brain changes after liver transplant depend on pretransplant cognitive impairment and are ultimately linked with posttransplant cognition and quality of life in cirrhosis. Liver Transplantation 22 1379-1390 2016 AASLD.

SUBMITTER: Ahluwalia V

PROVIDER: S-EPMC5036999 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Liver transplantation significantly improves global functioning and cerebral processing.

Ahluwalia Vishwadeep V Wade James B JB White Melanie B MB Gilles HoChong S HS Heuman Douglas M DM Fuchs Michael M Gavis Edith A EA Fagan Andrew A Tinsley Felicia F Ganapathy Dinesh D Thacker Leroy R LR Sterling Richard K RK Stravitz R Todd RT Puri Puneet P Sanyal Arun J AJ Siddiqui Muhammad S MS Matherly Scott S Luketic Velimir V Steinberg Joel J Moeller F Gerard FG Bajaj Jasmohan S JS

Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 20161001 10

The functional basis of cognitive and quality of life changes after liver transplant is unclear. We aimed to evaluate the neurometabolic and functional brain changes as modulators of cognition and quality of life after transplant in patients with cirrhosis who were with/without pretransplant cognitive impairment and hepatic encephalopathy (HE). Patients with cirrhosis underwent detailed cognitive and quality of life assessment at enrollment and 6 months after transplant. A subset underwent brain ...[more]

PMID: 27339647

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Project description:BackgroundThe initial dose of tacrolimus after liver transplantation (LT) is critical for rapidly achieving the steady state of the drug concentration, minimizing the potential adverse reactions and warranting long-term patient prognosis. We aimed to develop and validate a genotype-guided model for determining personalized initial dose of tacrolimus.MethodsBy combining pharmacokinetic modeling, pharmacogenomic analysis and multiple statistical methods, we developed a genotype-guided model to predict individualized tacrolimus initial dose after LT in the discovery (n = 150) and validation cohorts (n = 97) respectively. This model was further validated in a prospective, randomized and single-blind clinical trial from August, 2021 to February, 2022 (n = 40, ChiCTR2100050288).FindingsOur model included donor's and recipient's genotypes, recipient's weight and total bilirubin, which achieved an area under the curve of receiver operating characteristic curve (AUC of ROC) of 0.88 and 0.79 in the discovery and validation cohorts, respectively. We found that patients who were given tacrolimus within the recommended concentration range (RCR) (4-10 ng/mL), the new-onset metabolic syndromes are lower, especially for new-onset diabetes (p = 0.043). In the clinical trial, compared to those in experience-based (EB) group, patients in the model-based (MB) group were more likely to achieving the RCR (75% vs 40%, p = 0.025) with a more variable individualized dose (0.023-0.096 mg/kg/day vs 0.045-0.057 mg/kg/day). Moreover, significantly fewer medication adjustments were required for the MB group than the EB group (2.75 ± 2.01 vs 6.05 ± 3.35, p = 0.001).InterpretationOur genotype-based model significantly improved the initial dosing accuracy of tacrolimus and reduced the number of medication adjustments, which are critical for improving the prognosis of LT patients.FundingNational Natural Science Foundation of China, Shanghai three-year action plan, National Science and Technology Major Project of China.

Project description:Clinical monitoring of cerebral blood flow (CBF) autoregulation in patients undergoing liver transplantation may provide a means for optimizing blood pressure to reduce the risk of brain injury. The purpose of this pilot project is to test the feasibility of autoregulation monitoring with transcranial Doppler (TCD) and near-infrared spectroscopy (NIRS) in patients undergoing liver transplantation and to assess changes that may occur perioperatively.We performed a prospective observational study in 9 consecutive patients undergoing orthotopic liver transplantation. Patients were monitored with TCD and NIRS. A continuous Pearson's correlation coefficient was calculated between mean arterial pressure (MAP) and CBF velocity and between MAP and NIRS data, rendering the variables mean velocity index (Mx) and cerebral oximetry index (COx), respectively. Both Mx and COx were averaged and compared during the dissection phase, anhepatic phase, first 30 min of reperfusion, and remaining reperfusion phase. Impaired autoregulation was defined as Mx ? 0.4.Autoregulation was impaired in one patient during all phases of surgery, in two patients during the anhepatic phase, and in one patient during reperfusion. Impaired autoregulation was associated with a MELD score >15 (p = 0.015) and postoperative seizures or stroke (p < 0.0001). Analysis of Mx categorized in 5 mmHg bins revealed that MAP at the lower limit of autoregulation (MAP when Mx increased to ? 0.4) ranged between 40 and 85 mmHg. Average Mx and average COx were significantly correlated (p = 0.0029). The relationship between COx and Mx remained when only patients with bilirubin >1.2 mg/dL were evaluated (p = 0.0419). There was no correlation between COx and baseline bilirubin (p = 0.2562) but MELD score and COx were correlated (p = 0.0458). Average COx was higher for patients with a MELD score >15 (p = 0.073) and for patients with a neurologic complication than for patients without neurologic complications (p = 0.0245).These results suggest that autoregulation is impaired in patients undergoing liver transplantation, even in the absence of acute, fulminant liver failure. Identification of patients at risk for neurologic complications after surgery may allow for prompt neuroprotective interventions, including directed pressure management.

Project description:BackgroundIn the first weeks after liver transplantation about 30% of the patients develop a posttransplant encephalopathy. A posttransplant encephalopathy comprises metabolic-toxic caused symptoms such as disorientation, confusion, hallucinations, cognitive dysfunction and seizures. We hypothesize that alterations of cerebral metabolites before liver transplantation predispose posttransplant encephalopathy development after liver transplantation.Methods31 patients with chronic liver disease underwent magnetic resonance spectroscopy (MRS) before liver transplantation to assess glutamine/glutamate (Glx), myo-Inositol (mI), choline (Cho), creatine/phosphocreatine- and N-acetyl-aspartate/N-acetyl-aspartate-glutamate concentrations in the thalamus, lentiform nucleus and white matter. Of these, 14 patients underwent MRS additionally after liver transplantation. Furthermore, 15 patients received MRS only after liver transplantation. Patients' data were compared to 20 healthy age adjusted controls.ResultsPatients showed significantly increased Glx and decreased mI and Cho concentrations compared to controls before liver transplantation (p?0.01). The MRS values before liver transplantation of patients with posttransplant encephalopathy showed no significant difference compared to patients without posttransplant encephalopathy. Patients after liver transplantation showed increased Glx concentrations (p?0.01) compared to controls, however, patients with and without posttransplant encephalopathy did not differ. Patients with posttransplant encephalopathy who underwent MRS before and after liver transplantation showed a significant mI increase in all three brain regions (p<0.04) and Glx decrease in the lentiform nucleus after liver transplantation (p = 0.04) while patients without posttransplant encephalopathy only showed a mI increase in the thalamus (p = 0.04).ConclusionPatients with and without posttransplant encephalopathy showed no significant difference in cerebral metabolites before liver transplantation. However, the paired sub-analysis indicates that the extent of cerebral metabolite alterations in patients with liver cirrhosis might be critical for the development of posttransplant encephalopathy after liver transplantation.

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Liver transplantation significantly improves global functioning and cerebral processing.

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Liver transplantation significantly improves global functioning and cerebral processing.

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