Differential impact of hyponatremia and hepatic encephalopathy on health-related quality of life and brain metabolite abnormalities in cirrhosis

Abstract

Background & aims: 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.

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.