title: Reduced cortical thickness in patients with acute-on-chronic liver failure due to non-alcoholic etiology.
abstract: BACKGROUND
  Acute-on-chronic liver failure (ACLF) is a form of liver disease with high short-term mortality. ACLF offers considerable potential to affect the cortical areas by significant tissue injury due to loss of neurons and other supporting cells. We measured changes in cortical thickness and metabolites profile in ACLF patients following treatment, and compared it with those of age matched healthy volunteers.
  
  
  METHODS
  For the cortical thickness analysis we performed whole brain high resolution T1-weighted magnetic resonance imaging (MRI) on 15 ACLF and 10 healthy volunteers at 3T clinical MR scanner. Proton MR Spectroscopy ((1)H MRS) was also performed to measure level of altered metabolites. Out of 15 ACLF patients 10 survived and underwent follow-up study after clinical recovery at 3 weeks. FreeSurfer program was used to quantify cortical thickness and LC- Model software was used to quantify absolute metabolites concentrations. Neuropsychological (NP) test was performed to assess the cognitive performance in follow-up ACLF patients compared to controls.
  
  
  RESULTS
  Significantly reduced cortical thicknesses in multiple brain sites, and significantly decreased N-acetyl aspartate (NAA), myo-inositol (mI) and significantly increased glutamate/glutamine (glx) metabolites were observed in ACLF compared to those of controls at baseline study. Follow-up patients showed significant recovery in cortical thickness and Glx level, while NAA and mI were partially recovered compared to baseline study. When compared to controls, follow-up patients still showed reduced cortical thickness and altered metabolites level. Follow-up patients had abnormal neuropsychological (NP) scores compared to controls.
  
  
  CONCLUSIONS
  Neuronal loss as suggested by the reduced NAA, decreased cellular density due to increased cerebral hyperammonemia as supported by the increased glx level, and increased proinflammatory cytokines and free radicals may account for the reduced cortical thickness in ACLF patients. Presence of reduced cortical thickness, altered metabolites and abnormal NP test scores in post recovery subjects as compared to those of controls is associated with incomplete clinical recovery. The current imaging protocol can be easily implemented in clinical settings to evaluate and monitor brain tissue changes in patients with ACLF during the course of treatment.
authors.affiliation: Research Branch, Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar. syadav@sidra.org.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Yadav
authors.affiliation: Department of Radiology, Fortis Memorial Research Institute, Gurgaon, Haryana, India. rakeshree1@gmail.com.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Gupta
authors.affiliation: Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. profviveksaraswat@gmail.com.
authors.forename: Vivek A
authors.initials: VA
authors.lastname: Saraswat
authors.affiliation: Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. drmuralipgi@gmail.com.
authors.forename: Murali
authors.initials: M
authors.lastname: Rangan
authors.affiliation: Department of Radiological Sciences, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California, USA. albertthoma@gmail.com.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Thomas
authors.affiliation: Research Branch, Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar. srutella@sidra.org.
authors.forename: Sergio
authors.initials: S
authors.lastname: Rutella
authors.affiliation: Department of Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy. sdanese@hotmail.com.
authors.forename: Silvio
authors.initials: S
authors.lastname: Danese
authors.affiliation: Research Branch, Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar. ewang@sidra.org.
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.affiliation: Research Branch, Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar. fmarincola@sidra.org.
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.affiliation: Research Branch, Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar. mharis@sidra.org.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Haris
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000150:complications / Q000503:physiopathology*; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D003071:Cognition; D003072:Cognition Disorders / Q000150:complications; D005260:Female; D005500:Follow-Up Studies; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000378:metabolism; D008099:Liver / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012984:Software; D016896:Treatment Outcome
chemical_list: D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D007294:Inositol; C000179:N-acetylaspartate