OBJECTIVES: I. Assess the effect of lactulose on the circadian rhythm of plasma melatonin in patients with subclinical hepatic encephalopathy.

II. Assess the intrasubject variability of circadian melatonin levels and neuropsychological tests.

III. Assess which elements of the neuropsychological test battery show the response to lactulose.

PROTOCOL OUTLINE: Patients are alternately assigned to 1 of 2 treatment groups: no therapy for 3 weeks followed by lactulose for 3 weeks versus lactulose for 3 weeks followed by no therapy for 3 weeks.

A dietician advises patients on a 1 g/kg per day protein diet. The lactulose dose is adjusted to result in 2 or 3 loose bowel movements per day.

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Clinical diagnosis of cirrhosis with portal hypertension or portal-systemic shunting

--Prior/Concurrent Therapy--

• No concurrent therapy for hepatic encephalopathy

--Patient Characteristics--

• Age: Under 65
• Performance status: Not specified
• Hematopoietic: Not specified
• Hepatic: See Disease Characteristics
• Renal: Not specified
• Other: No alcohol intake within 1 month prior to entry No requirement for beta blockers No requirement for corticosteroids Not in intercontinental travel