The Neuroprotective Power of Artificial Liver Therapy: Reversing Cognitive Impairment in Minimal Hepatic Encephalopathy

Overview

Journal Brain Imaging Behav

Publisher Springer

Specialties Neurology
Psychology
Radiology
Social Sciences

Date 2025 Mar 5

PMID 40042700

Authors

Xiaodong Wang

Xuhong Yang

Minglei Wang

Xueying Huang

Ming Zhang

Affiliations

Soon will be listed here.

Abstract

Alteration of functional connectivity in brain regions is one of the potential neuropathological mechanisms underlying cognitive impairment in patients with minimal hepatic encephalopathy (MHE). Artificial liver therapy has been shown to improve cognitive impairment in patients, suggesting a potential neuroprotective effect on the brain. This study investigates the impact of artificial liver therapy (AL) on cognitive impairment in patients with minimal hepatic encephalopathy (MHE) by examining alterations in brain functional connectivity. Resting-state functional magnetic resonance imaging (fMRI) data was collected from healthy controls and MHE patients before and after therapy. The MHE group showed improved memory, reaction time, and executive function compared to the MHE group. Functional connectivity analysis revealed increased connectivity in specific brain regions in the MHE group compared to healthy controls, with subsequent decreased connectivity after therapy. Lower MoCA scores, higher blood ammonia levels, and lower cholinesterase levels were associated with higher functional connectivity in the MHE group. The study suggests that artificial liver therapy improves cognitive impairment in MHE patients, with changes in blood biochemistry mediating the link between functional connectivity and cognitive function. Correcting blood biochemistry levels may reverse abnormal brain connectivity and enhance cognitive function in MHE patients.

References

Amodio P, Cordoba J . Smart applications for assessing minimal hepatic encephalopathy: novelty from the app revolution. Hepatology. 2013; 58(3):844-6. DOI: 10.1002/hep.26416. View

Dhiman R, Thumburu K, Verma N, Chopra M, Rathi S, Dutta U . Comparative Efficacy of Treatment Options for Minimal Hepatic Encephalopathy: A Systematic Review and Network Meta-Analysis. Clin Gastroenterol Hepatol. 2019; 18(4):800-812.e25. DOI: 10.1016/j.cgh.2019.08.047. View

Fox M, Snyder A, Vincent J, Corbetta M, Van Essen D, Raichle M . The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A. 2005; 102(27):9673-8. PMC: 1157105. DOI: 10.1073/pnas.0504136102. View

Goyal O, Sidhu S, Kishore H . Minimal hepatic encephalopathy in cirrhosis- how long to treat?. Ann Hepatol. 2017; 16(1):115-122. DOI: 10.5604/16652681.1226822. View

Ha Z, Mathew S, Yeong K . Butyrylcholinesterase: A Multifaceted Pharmacological Target and Tool. Curr Protein Pept Sci. 2019; 21(1):99-109. DOI: 10.2174/1389203720666191107094949. View

Hazra D, Yoshinaga S, Yoshida K, Takata N, Tanaka K, Kubo K . Rhythmic activation of excitatory neurons in the mouse frontal cortex improves the prefrontal cortex-mediated cognitive function. Cereb Cortex. 2022; 32(23):5243-5258. DOI: 10.1093/cercor/bhac011. View

Jepsen P, Younossi Z . The global burden of cirrhosis: A review of disability-adjusted life-years lost and unmet needs. J Hepatol. 2021; 75 Suppl 1:S3-S13. DOI: 10.1016/j.jhep.2020.11.042. View

Li P, Ma S, Ma X, Ding D, Zhu X, Zhang H . Reversal of neurovascular decoupling and cognitive impairment in patients with end-stage renal disease during a hemodialysis session: Evidence from a comprehensive fMRI analysis. Hum Brain Mapp. 2022; 44(3):989-1001. PMC: 9875915. DOI: 10.1002/hbm.26122. View

Mas A . Hepatic encephalopathy: from pathophysiology to treatment. Digestion. 2006; 73 Suppl 1:86-93. DOI: 10.1159/000089783. View

10.

Mesulam M, Guillozet A, Shaw P, Quinn B . Widely spread butyrylcholinesterase can hydrolyze acetylcholine in the normal and Alzheimer brain. Neurobiol Dis. 2002; 9(1):88-93. DOI: 10.1006/nbdi.2001.0462. View

11.

Nasreddine Z, Phillips N, Bedirian V, Charbonneau S, Whitehead V, Collin I . The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005; 53(4):695-9. DOI: 10.1111/j.1532-5415.2005.53221.x. View

12.

Ni L, Wen J, Zhang L, Zhu T, Qi R, Xu Q . Aberrant default-mode functional connectivity in patients with end-stage renal disease: a resting-state functional MR imaging study. Radiology. 2014; 271(2):543-52. DOI: 10.1148/radiol.13130816. View

13.

Prasad S, Dhiman R, Duseja A, Chawla Y, Sharma A, Agarwal R . Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy. Hepatology. 2007; 45(3):549-59. DOI: 10.1002/hep.21533. View

14.

Sidhu S, Goyal O, Parker R, Kishore H, Sood A . Rifaximin vs. lactulose in treatment of minimal hepatic encephalopathy. Liver Int. 2015; 36(3):378-85. DOI: 10.1111/liv.12921. View

15.

Stadlbauer V, Davies N, Sen S, Jalan R . Artificial liver support systems in the management of complications of cirrhosis. Semin Liver Dis. 2008; 28(1):96-109. DOI: 10.1055/s-2008-1040324. View

16.

Stadlbauer V, Wright G, Jalan R . Role of artificial liver support in hepatic encephalopathy. Metab Brain Dis. 2008; 24(1):15-26. DOI: 10.1007/s11011-008-9117-2. View

17.

Wang J, Zhang N, Chi B, Mi Y, Meng L, Liu Y . Prevalence of minimal hepatic encephalopathy and quality of life evaluations in hospitalized cirrhotic patients in China. World J Gastroenterol. 2013; 19(30):4984-91. PMC: 3740430. DOI: 10.3748/wjg.v19.i30.4984. View

18.

Wang Y, Zhong S, Jia Y, Sun Y, Wang B, Liu T . Disrupted Resting-State Functional Connectivity in Nonmedicated Bipolar Disorder. Radiology. 2016; 280(2):529-36. DOI: 10.1148/radiol.2016151641. View

19.

Wang Y, Yang X, Xiao L, Li W, Huo X, Wang C . Altered anterior insula-superior frontal gyrus functional connectivity is correlated with cognitive impairment following total sleep deprivation. Biochem Biophys Res Commun. 2022; 624:47-52. DOI: 10.1016/j.bbrc.2022.07.078. View

20.

Xu J, Lyu H, Li T, Xu Z, Fu X, Jia F . Delineating functional segregations of the human middle temporal gyrus with resting-state functional connectivity and coactivation patterns. Hum Brain Mapp. 2019; 40(18):5159-5171. PMC: 6865466. DOI: 10.1002/hbm.24763. View