Background:

- Fatigue is a common and often disabling symptom in people with chronic liver disease. Its causes are not well understood. Sleep disturbance may play a role in people with cirrhosis, but these factors have not been studied in people with other stages of liver disease. This study will look at the body's circadian rhythms (internal clock) to see if problems with these rhythms can contribute to fatigue. It will look at the causes and mechanisms of fatigue in people with chronic liver disease by comparing people with and without fatigue.

Objectives:

- To study reasons for fatigue in people with chronic liver disease.

Eligibility:

• <TAB>Individuals at least 18 years of age who have chronic liver disease.
• <TAB>Participants with or without fatigue may enroll.

Design:

• Participants will be screened with a physical exam and medical history. They will have a 2-day inpatient stay for the study.
• For the 7 days before the inpatient stay, participants will keep a sleep diary. They will record any caffeine or alcohol consumption, medicines, exercise, and sleep or naps. They will also wear an actigraph to measure their activity levels.
• During the inpatient stay, participants will answer questions about fatigue and sleep habits. They will have regular blood tests for 24 hours. Their body temperature will also be monitored. During the night, they will have a sleep study to look at how well or poorly they sleep.
• Treatment will not be provided as part of this study.

Fatigue is a common symptom in patients with chronic liver disease, and can severely impact quality of life. Thus far, there is scant knowledge about the causes of fatigue in this population, and almost no specific treatments for fatigue have been found effective in clinical trials. Sleep disturbance and alterations in plasma melatonin profiles have been documented in patients with cirrhosis, but remain largely unstudied in patients with earlier stages of liver disease. Up to 50 patients will be enrolled in a case-control study on the physiology of fatigue in patients with chronic liver disease. This is a descriptive study, exploring the concept that fatigue may be the result of circadian rhythms in the central nervous system being out of sync with circadian rhythms in peripheral organs, i.e. unsynchronized central and peripheral clocks.

• INCLUSION CRITERIA:
• Adults (age >18) with chronic liver disease of any etiology

EXCLUSION CRITERIA:

• Treatment with medications or supplements frequently associated with fatigue, such as interferon (within the last four months), beta-blockers, calcium channel blockers, benzodiazepines, sedating antihistamines, antidepressants, antipsychotics, or melatonin. In select instances, patients using these medications may be enrolled if, in the opinion of the investigators, their fatigue is clearly unrelated to the medication.
• Untreated or uncontrolled comorbidities that influence fatigue, including thyroid disorders (TSH>5 mcIU/mL), anemia (Hemoglobin<11 g/dL), major depression, active substance abuse or other conditions as determined by the enrolling physician. Comorbidities that are adequately controlled will not exclude patients.
• Untreated sleep disorders such as obstructive sleep apnea or restless leg syndrome
• Decompensated cirrhosis (encephalopathy, gastrointestinal bleeding, ascites, bilirubin >2) within the last six months
• Patients planning to travel outside the time zone during the study period
• Known or suspected significant gastrointestinal motility disorder, obstruction, or structuring disease
• Pregnancy, breastfeeding, or intention to become pregnant
• Inability to provide informed consent