Liver transplantation significantly improves global functioning and cerebral processing

Abstract

The functional basis of cognitive and quality of life (QOL) change after liver transplant is unclear. We aimed to evaluate the neuro-metabolic and functional brain changes as modulators of cognition and QOL post-transplant in cirrhotics with/without pre-transplant cognitive impairment and hepatic encephalopathy (HE). Cirrhotics underwent detailed cognitive and QOL assessment at enrollment and six months post-transplant. A subset underwent brain MRI [Functional (fMRI), diffusion tensor imaging (DTI) and spectroscopy(MRS)] pre/post-transplant. Changes pre/post-transplant were analyzed in all patients and by dividing groups in those with/without pre-transplant cognitive impairment, or with/without pre-transplant HE. fMRI studied brain activation for correct lure inhibition on inhibitory control test, MRS evaluated ammonia-related metabolites and DTI studied white matter integrity. Sixty-six patients (MELD 21.8, 38 HE, 24 cognitively impaired) were enrolled. QOL was significantly worse in cognitively impaired and HE groups pre-transplant, which improved to a lesser extent in those with prior cognitive impairment. In the entire group post-transplant there was (i) fMRI: significantly lower brain activation needed for lure inhibition (ii) MRS: reversal of pre-transplant ammonia-associated changes and (iii) DTI: improved white matter integrity. Importantly, study findings suggest that pre-transplant cognitive impairment serves as a marker for clinical outcomes. Regardless of pre-transplant history of HE, it was the pre-transplant cognitive impairment that was predictive of both post-transplant cognitive and psychosocial outcomes. Therefore, when working with patients and their families a clinician may rely on the pre-transplant cognitive profile to develop expectations regarding post-transplant neurobehavioral recovery. We conclude that functional brain changes after liver transplant depend on pre-transplant cognitive impairment and ultimately are linked with post-transplant cognition and QOL in cirrhosis.

Longterm calcineurin inhibitor therapy and brain function in patients after liver transplantation

“…It is assumed that after OLT, HE‐associated cognitive dysfunction recovers. Ahluwalia et al showed an improvement of cognitive function and cerebral magnetic resonance spectroscopy from before OLT to 6 months after OLT in 66 patients of which 38 had a history of HE before OLT . However, 21% of the patients still showed cognitive impairment after OLT.…”

“…Ahluwalia et al showed an improvement of cognitive function and cerebral magnetic resonance spectroscopy from before OLT to 6 months after OLT in 66 patients of which 38 had a history of HE before OLT. (23) However, 21% of the patients still showed cognitive impairment after OLT. Campagna et al as well showed cognitive improvement 9-12 months after OLT in 65 patients of which 23 had a history of HE before OLT.…”

Overt hepatic encephalopathy impairs learning on the EncephalApp stroop which is reversible after liver transplantation

“…Prior studies have shown OHE patients have a variable outcome post-transplant(22, 26). A recent study demonstrated that a simple pre-transplant OHE diagnosis was not a powerful predictor of post-transplant cognitive impairment on multi-modal MR imaging(27, 28). Therefore, the restoration of this learning ability points towards a hopeful illness course after transplant in these patients.…”

“…Indeed, in an fMRI study examining the functional basis of cognitive change after liver transplantation Ahluwalia et al, found robust activation in areas within the dorsolateral prefrontal cortex and anterior cingulate cortex(27). These brain regions are hypothesized to underlie successful Stroop test performance.…”

“…These data speak to a remarkable resiliency of brain function. Since our focus was on evaluation of OHE patients’ recovery, the longitudinal studies had adequate numbers of OHE patients based on prior experiences, however the patients without OHE may be lower than required to definitively make the conclusions longitudinally(4, 27). However, prior data and cross-sectional analyses would not necessarily predict changes in no-OHE patients over time.…”