title: Correction of hyponatraemia improves cognition, quality of life, and brain oedema in cirrhosis.
abstract: OBJECTIVE
  Hyponatraemia in cirrhosis is associated with impaired cognition and poor health-related quality of life (HRQOL). However, the benefit of hyponatraemia correction is unclear. The aim of this study was to evaluate the effect of tolvaptan on serum sodium (Na), cognition, HRQOL, companion burden, and brain MRI (volumetrics, spectroscopy, and diffusion tensor imaging) in cirrhotics with hyponatraemia.
  
  
  METHODS
  Cirrhotics with Na <130 mEq/L were included for a four-week trial. At screening, patients underwent cognitive and HRQOL testing, serum/urine chemistries and companion burden assessment. Patients then underwent fluid restriction and diuretic withdrawal for two weeks after which cognitive tests were repeated. If Na was still <130 mEq/L, brain magnetic resonance imaging (MRI) was performed and tolvaptan was initiated for 14 days with frequent clinical/laboratory monitoring. After 14 days of tolvaptan, all tests were repeated. Comparisons were made between screen, pre-and post-drug periods Na, urine/serum laboratories, cognition, HRQOL and companion burden.
  
  
  RESULTS
  24 cirrhotics were enrolled; seven normalized Na without tolvaptan with improvement in cognition. The remaining 17 received tolvaptan of which 14 completed the study over 13 ± 2 days (age 58 ± 6 years, MELD 17, 55% HCV, median 26 mg/day of tolvaptan). Serum Na and urine free water clearance increased with tolvaptan without changes in mental status or liver function. Cognitive function, HRQOL and companion burden only improved in these 14 patients after tolvaptan, along with reduced total brain and white matter volume, increase in choline on magnetic resonance spectroscopy, and reduced cytotoxic oedema.
  
  
  CONCLUSIONS
  Short-term tolvaptan therapy is well tolerated in cirrhosis. Hyponatraemia correction is associated with cognitive, HRQOL, brain MRI and companion burden improvement.
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA; Department of Radiology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Vishwadeep
authors.initials: V
authors.lastname: Ahluwalia
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Heuman
authors.affiliation: Department of Nephrology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: George
authors.initials: G
authors.lastname: Feldman
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Wade
authors.affiliation: Department of Biostatistics, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Leroy R
authors.initials: LR
authors.lastname: Thacker
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Edith
authors.initials: E
authors.lastname: Gavis
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: HoChong
authors.initials: H
authors.lastname: Gilles
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Unser
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Melanie B
authors.initials: MB
authors.lastname: White
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA. Electronic address: jsbajaj@vcu.edu.
authors.forename: Jasmohan S
authors.initials: JS
authors.lastname: Bajaj
mesh_terms: D065092:Antidiuretic Hormone Receptor Antagonists / Q000008:administration & dosage; D001552:Benzazepines / Q000008:administration & dosage*; D001929:Brain Edema / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D003071:Cognition; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007010:Hyponatremia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000150:complications*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012964:Sodium / Q000097:blood / Q000652:urine; D000077602:Tolvaptan; D016896:Treatment Outcome
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D000077602:Tolvaptan; D012964:Sodium
keywords: Aquaresis; Caregiver burden; Diffusion tensor imaging; Hepatic encephalopathy; Magnetic resonance spectroscopy; Tolvaptan
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