title: Differential impact of hyponatremia and hepatic encephalopathy on health-related quality of life and brain metabolite abnormalities in cirrhosis.
abstract: OBJECTIVE
  Hyponatremia (HN) and hepatic encephalopathy (HE) together can impair health-related quality of life (HRQOL) and cognition in cirrhosis. We aimed at studying the effect of hyponatremia on cognition, HRQOL, and brain MR spectroscopy (MRS) independent of HE.
  
  
  METHODS
  Four cirrhotic groups (no HE/HN, HE alone, HN alone (sodium <130 mEq/L), HE+HN) underwent cognitive testing, HRQOL using Sickness Impact Profile (SIP: higher score is worse; has psychosocial and physical sub-scores) and brain MRS (myoinositol (mI) and glutamate+glutamine (Glx)), which were compared across groups. A subset underwent HRQOL testing before/after diuretic withdrawal.
  
  
  RESULTS
  82 cirrhotics (30 no HE/HN, 25 HE, 17 HE+HN, and 10 HN, MELD 12, 63% hepatitis C) were included. Cirrhotics with HN alone and without HE/HN had better cognition compared to HE groups (median abnormal tests no-HE/HN: 3, HN: 3.5, HE: 6.5, HE+HN: 7, p=0.008). Despite better cognition, HN only patients had worse HRQOL in total and psychosocial SIP while both HN groups (with/without HE) had a significantly worse physical SIP (p<0.0001, all comparisons). Brain MRS showed the lowest Glx in HN and the highest in HE groups (p<0.02). mI levels were comparably decreased in the three affected (HE, HE+HN, and HN) groups compared to no HE/HN and were associated with poor HRQOL. Six HE+HN cirrhotics underwent diuretic withdrawal which improved serum sodium and total/psychosocial SIP scores.
  
  
  CONCLUSIONS
  Hyponatremic cirrhotics without HE have poor HRQOL despite better cognition than those with concomitant HE. Glx levels were lowest in HN without HE but mI was similar across affected groups. HRQOL improved after diuretic withdrawal. Hyponatremia has a complex, non-linear relationship with brain Glx and mI, cognition and HRQOL.
authors.affiliation: Radiology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Vishwadeep
authors.initials: V
authors.lastname: Ahluwalia
authors.forename: James B
authors.initials: JB
authors.lastname: Wade
authors.forename: Leroy
authors.initials: L
authors.lastname: Thacker
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Kraft
authors.forename: Richard K
authors.initials: RK
authors.lastname: Sterling
authors.forename: R Todd
authors.initials: RT
authors.lastname: Stravitz
authors.forename: Michael
authors.initials: M
authors.lastname: Fuchs
authors.forename: Iliana
authors.initials: I
authors.lastname: Bouneva
authors.forename: Puneet
authors.initials: P
authors.lastname: Puri
authors.forename: Velimir
authors.initials: V
authors.lastname: Luketic
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Sanyal
authors.forename: Hochong
authors.initials: H
authors.lastname: Gilles
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Heuman
authors.forename: Jasmohan S
authors.initials: JS
authors.lastname: Bajaj
mesh_terms: D001921:Brain / Q000378:metabolism*; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism / Q000523:psychology; D004232:Diuretics / Q000008:administration & dosage; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000150:complications* / Q000378:metabolism* / Q000523:psychology; D006801:Humans; D007010:Hyponatremia / Q000150:complications* / Q000378:metabolism* / Q000523:psychology; D007294:Inositol / Q000378:metabolism; D008103:Liver Cirrhosis / Q000150:complications* / Q000378:metabolism* / Q000523:psychology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D018434:Sickness Impact Profile
chemical_list: D004232:Diuretics; D005973:Glutamine; D018698:Glutamic Acid; D007294:Inositol
keywords: ACC; BDT; CHESS; Cho; Cognitive function; Cr; DST; Glx; HE; HE+HN; HN; HRQOL; Hepatic encephalopathy; Hyponatremia; ICT; LTTt/e; MELD; MMSE; MRI; MRS; Magnetic resonance spectroscopy; Model for End-Stage Liver Disease; N; NCT-A/B; OGM; PHES; PRESS; RPWM; SDT; SIP; Sickness Impact Profile; TIPS; VOI; anterior cingulate cortex; block design test; choline; clinical hepatic encephalopathy staging scale; creatine; digit symbol test; glutamate+glutamine; health-related quality of life; hepatic encephalopathy; hepatic encephalopathy and hyponatremia; hyponatremia; inhibitory control test; line tracing test time/errors; mI; magnetic resonance imaging; magnetic resonance spectroscopy; mini-mental status examination; myoinositol; neither HE nor hyponatremia; number connection tests A/B; occipital gray matter; point resolved spectroscopy; psychometric hepatic encephalopathy score; right parietal white matter; serial dotting test; sickness impact profile; transjugular intra-hepatic porto-systemic shunting; voxel of interest