Effect of Tolvaptan on Cognitive Function in Cirrhosis
Effect of Tolvaptan on Cognitive Function in Cirrhosis
Hypothesis: Tolvaptan will improve cognitive function, brain edema and health-related quality
 of life in cirrhotic patients with hyponatremia
Baseline assessment will include a

 1. battery of eight cognitive tests

 2. Health related quality of life

 3. MRI head evaluating MR spectroscopy and diffusion tensor imaging

 Patients will then be given tolvaptan 15-30mg qd for 14 days after which the tests will be
 repeated. During the first 3 days of tolvaptan administration, patients will be admitted and
 serum sodium will be drawn every 8 hours. 24 hr urine collection will also be performed.

 Between the initiation and end of tolvaptan, patients will be seen at least every 3-5 days in
 between.

 Participation will be terminated in case patients get transplanted or develop overt HE in
 between.
Inclusion Criteria:

 -  Cirrhosis diagnosed by liver biopsy or radiological evidence of nodular cirrhotic
 liver or varices on endoscopy or laboratory features (platelet count <150,000 with an
 AST/ALT ratio >1).

 -  History of HE controlled on lactulose and/or rifaximin

 -  Last HE episode >2 months prior to enrollment and <2 episodes within 6 months

 -  Mini-mental status exam score ≥25

 -  Serum sodium <130mg/dl within the last 14 days and the day of enrollment

 -  Availability of a caregiver

 -  Able to undergo MR of the head

 Exclusion Criteria:

 -  Uncontrolled HE manifested by MMSE <25

 -  Alcohol abuse within 3 months

 -  Illicit drug use within 3 months

 -  Psychoactive drug use other than regularly scheduled anti-depressants or methadone.

 -  Contraindication to MR examination (see attached MRI Safety Form)

 -  Placement of a transjugular intra-hepatic portosystemic shunt (TIPS)

 -  Creatinine Clearance less than 10 ml/min or undergoing hemodialysis

 -  HIV infection

 -  Use of azole medications

 -  Pregnancy

 -  Current use of tolvaptan, hypertonic saline or other medical therapies for
 hyponatremia