Correction of hyponatraemia improves cognition, quality of life, and brain oedema in cirrhosis

J Hepatol. 2015 Jan;62(1):75-82. doi: 10.1016/j.jhep.2014.07.033. Epub 2014 Aug 8.


Background & aims: 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.

Keywords: Aquaresis; Caregiver burden; Diffusion tensor imaging; Hepatic encephalopathy; Magnetic resonance spectroscopy; Tolvaptan.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidiuretic Hormone Receptor Antagonists / administration & dosage
  • Benzazepines / administration & dosage*
  • Brain Edema / diagnosis
  • Brain Edema / drug therapy
  • Brain Edema / etiology*
  • Cognition*
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Hyponatremia / complications
  • Hyponatremia / drug therapy*
  • Hyponatremia / metabolism
  • Liver Cirrhosis / complications*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Quality of Life*
  • Sodium / blood
  • Sodium / urine
  • Tolvaptan
  • Treatment Outcome


  • Antidiuretic Hormone Receptor Antagonists
  • Benzazepines
  • Tolvaptan
  • Sodium