Hyponatremia Correction in Cirrhosis May Improve Cognition, Reduce Caregiver Burden

Investigating the association between hyponatremia and cognition in patients with cirrhosis, Jasmohan Bajaj, MD, and colleagues from Virginia Commonwealth University presented results showing reduced brain edema, better quality of life (QOL), and less caregiver burden with the use of the aquaretic tolvaptan.

Tolvaptan, a selective, competitive vasopressin receptor 2 antagonist, can correct hyponatremia by causing aquaresis with electrolyte sparing. However, earlier this year, the US Food and Drug Administration (FDA) removed the indication for use of tolvaptan in patients with cirrhosis, citing concerns about liver injury with use of tolvaptan.

For a poster presented by Bajaj during the 2013 annual meeting of the American Association for the Study of Liver Disease (AASLD), held November 1-5, 2013, in Washington, DC, patients with cirrhosis and hyponatremia — defined as serum sodium <130meq/L &mdash; were enrolled in a 4-week trial. Baseline psychologic and psychosocial evaluation included cognitive testing, QOL evaluation using the Chronic Liver Disease Questionnaire (CLDQ), and caregiver burden evaluated with the Perceived Caregiver Burden (PCB).

Diuretic cessation and fluid withdrawal began after baseline evaluation, and subjects who remained hyponatremic at week 2 received magnetic resonance (MR) brain imaging, repeat evaluation of psychologic and psychosocial status, and tolvaptan treatment. All evaluation procedures and laboratory studies were repeated at the end of week 4.

Brain imaging modalities used for evaluation included MR spectroscopy, voxel-based morphometry (VBM) to measure volumes of both the brain and CSF spaces, and diffusion tensor imaging (DTI) to measure fractional anisotropy (FA) and mean diffusivity (MD).

Of the 17 subjects who remained hyponatremic at week 2 of the study, 2 withdrew. The 15 remaining subjects with a mean age of 58 maintained stable liver disease evaluation and mental status while taking the drug.

Further data analysis comparing data obtained at week 0, week 2, and week 4 showed significant improvement in hyponatremia, hyperammonemia, and selected cognitive tests during tolvaptan administration between weeks 2 and 4, but not in the pre-drug state between weeks 0 and 2.

Mean sodium levels of 124 meq/L at week 0 and 126 meq/L at week 2 reached 133 meq/L by the end of week 4. Ammonia levels were an average of 63.3 mcg/dL at week 0, which remained unchanged at week 2, but fell to 44 mcg/dL by the end of week 4.

Improvements in the CLDQ and PCB questionnaires were significant, indicating both patients and caregivers saw improvement during tolvaptan administration.

MR spectroscopy of the brain showed increases in choline in the examined areas of the brain, which was indicative of reduced brain edema. DTI showed some reduction in FA of the genu of the corpus callosum, but no change in mean MD values with tolvaptan administration. At the end of week 4, VBM showed no change in total gray matter volume or total brain volume, and no significant change in total CSF volume or white matter volume.