Effect of Tolvaptan on Cognitive Function in Cirrhosis

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