Renormalization of Thalamic Sub-Regional Functional Connectivity Contributes to Improvement of Cognitive Function after Liver Transplantation in Cirrhotic Patients with Overt Hepatic Encephalopathy

Abstract

Objective The role of preoperative overt hepatic encephalopathy (OHE) in the neurophysiological mechanism of cognitive improvement after liver transplantation (LT) remains elusive. This study aimed to explore changes in sub-regional thalamic functional connectivity (FC) after LT and their relationship with neuropsychological improvement using resting-state functional MRI (rs-fMRI) data in cirrhotic patients with and without a history of OHE. Materials and Methods A total of 51 cirrhotic patients, divided into the OHE group (n = 21) and no-OHE group (n = 30), and 30 healthy controls were enrolled in this prospective study. Each patient underwent rs-fMRI before and 1 month after LT. Using 16 bilateral thalamic subregions as seeds, we conducted a seed-to-voxel FC analysis to compare the thalamic FC alterations before and after LT between the OHE and no-OHE groups, as well as differences in FC between the two groups of cirrhotic patients and the control group. Correction for multiple comparisons was conducted using the false discovery rate ( p < 0.05). Results We found abnormally increased FC between the thalamic sub-region and prefrontal cortex, as well as an abnormally decreased FC between the bilateral thalamus in both OHE and no-OHE cirrhotic patients before LT, which returned to normal levels after LT. Compared with the no-OHE group, the OHE group exhibited more extensive abnormalities prior to LT, and the increased FC between the right thalamic subregions and right inferior parietal lobe was markedly reduced to normal levels after LT. Conclusion The renormalization of FC in the cortico-thalamic loop might be a neuro-substrate for the recovery of cognitive function after LT in cirrhotic patients. In addition, hyperconnectivity between thalamic subregions and the inferior parietal lobe might be an important feature of OHE. Changes in FC in the thalamus might be used as potential biomarkers for recovery of cognitive function after LT in cirrhotic patients.

Cognitive Impairment in Liver Transplant Recipients With a History of Cirrhosis: A Systematic Review

“…Of the 24 studies included, 19 (79%) provided data that could be mapped to 6 distinct cognitive domains (attention, executive function, working memory, long-term memory, visuospatial, and language) summarized below (Table 3). 2,3,7–9,27–39,42…”

“…Of the 24 included studies, 23 (96%) were prospective cohort studies with duration of follow-up ranging from 1 mo to 1.8 y after LT. 1,2,5,[7][8][9][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] The median number of patients in the included studies was 30 (interquartile range: 21.5-50.5). Ten (42%) studies were conducted in Europe, 2,9,26,[33][34][35][36][40][41][42] 9 (38%) in Asia, 8,[27][28][29][30][31][32]38,39 and 5 (21%) in the United States. 1,3,5,7,37 Twenty-three studies (96%) reported the mean or median age, which was between 31 and 65 y.…”

“…The NOS tool was used to assess the risk of bias in the 18 prospective cohort studies. One study was assessed as low quality, 36 16 as moderate quality, 5,7,8,[27][28][29][30][31][32][33][34][35]38,39,41,42 and 6 as high quality. 1,2,9,26,37,40 The AXIS tool was used to assess the risk of bias in the 1 cross-sectional study, which met all 20 criteria for quality (Table 2).…”

“…Of the 24 included studies, 23 (96%) were prospective cohort studies with duration of follow-up ranging from 1 mo to 1.8 y after LT. 1,2,5,[7][8][9][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] The median number of patients in the included studies was 30 (interquartile range: 21.5-50.5). Ten (42%) studies were conducted in Europe, 2,9,26,[33][34][35][36][40][41][42] 9 (38%) in Asia, 8,[27][28][29][30][31][32]38,39 and 5 (21%) in the United States.…”

“…1,3,5,7,37 Twenty-three studies (96%) reported the mean or median age, which was between 31 and 65 y. 3,5,[7][8][9][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] Seventeen studies (71%) reported data on the etiology of liver cirrhosis [1][2][3]5,[7][8][9]26,29,30,[33][34][35][36][37]40,41 while 8 (33%) reported the mean or median MELD score (Table 1). [1][2][3]5,7,9,37,…”