The Effect of a Large-volume Paracentesis on Fatigue, Sleep, and Quality of Life in Cirrhosis

The study design is a prospective observational analysis. Subjects who have been deemed
candidates for a large-volume paracentesis, based on clinical criteria and who meet the
above-referenced inclusion and exclusion criteria will be recruited to participate in this
study. Study visits will take place on 2 consecutive days. Each study visit will last
approximately 2 to 3 hours. The first assessment day will occur immediately prior to an
electively-scheduled large-volume paracentesis. The second assessment will occur one day
later.

Once enrolled, all subjects will undergo a baseline assessment of liver function. Medical
records will be reviewed to determine etiology of cirrhosis, history of variceal bleeding,
history of spontaneous bacterial peritonitis, history of hospitalization for hepatic
encephalopathy, and use of and clinical response to treatment with lactulose, neomycin,
and/or rifaximin. Body mass index and grade of ascites (grade 1, mild ascites; grade 2,
moderate ascites; grade 3, massive or tense ascites) will be determined based on physical
examination. History or presence of asterixis will be recorded. Severity of hepatic
encephalopathy will be graded according to the West-Haven criteria and further assessed by
neuropsychological testing (discussed in further detail below). Baseline serum laboratory
analyses will be obtained, including the following: aspartate aminotransferase, alanine
aminotransferase, total bilirubin, albumin, blood urea nitrogen, creatinine, prothrombin
time and international normalized ratio, and platelet count. Based on these serum studies,
the Child-Pugh score and Model for End-Stage Liver Disease score will be calculated.

After baseline assessments are obtained, the six-minute walk test and a series of
questionnaires (discussed in further detail below) to assess fatigue, sleep, and quality of
life will be performed on study day 1, immediately prior to the paracentesis, and then
repeated one day after the paracentesis. Note that neither the six-minute walk test nor the
neuropsychological testing or questionnaires are considered standard of care for patients
requiring large-volume paracentesis and these will be performed exclusively for research
purposes.

Inclusion Criteria:

Subjects with cirrhosis (based on clinical, laboratory, radiologic evaluation, and liver
biopsy, when available) with diuretic-resistant refractory ascites, based on International
Ascites Club criteria.[2,31] Specific criteria used for inclusion will be subjects with
ascites that cannot be stabilized despite intensive diuretic therapy (e.g., 400 mg of
spironolactone with 160 mg of furosemide per day) and dietary sodium restriction (90 mmol
of sodium per day) with reappearance of grade 2 or 3 ascites within 4 weeks of
mobilization (defined as decrease of ascites at least to grade 1). All subjects must
provide separate written consent to undergo a large-volume paracentesis.

Exclusion Criteria:

Subjects will not be eligible for the study if they: (1) have been hospitalized in the
previous 1 month for gastrointestinal bleeding, infection, or renal failure; (2) are
unable to independently ambulate or have had unstable angina or myocardial infarction
within the previous 1 month, as these are contraindications to participating in the
6-minute walk test; (3) are unable to participate in neuropsychological tests or
questionnaires; (4) are receiving interferon therapy; (5) have a history of alcohol abuse
within the previous 6 months; (6) have a diagnosis of a primary neurologic disorder or
uncontrolled psychiatric disorder; or (7) are receiving psychotropic medications such as
benzodiazepines and anti-epileptic drugs.