Effect of Tolvaptan on Cognitive Function in Cirrhosis

Effects of Tolvaptan on Cognitive Function, Brain Metabolism and Quality of Life in Hyponatremic Cirrhotics With Hepatic Encephalopathy: A Prospective Clinical Trial

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