Albumina ad alto dosaggio nell'ascite refrattaria

Patients with advanced liver disease often has low serum albumin level. The Infusion of human albumin is a standard of care after removal of ascitic fluid in patients with cirrhosis with refractory ascites. The objective of the study is to prove that regular infusion of albumin prevents formation of fluid in abdomen (ascites) or pleural fluid (Hydrothorax) and thus reduces the requirement of paracentesis or thoracentesis, and prevent complications.

The Primary endpoints are: (1) Number of paracentesis/thoracentesis needed and volume of fluid removed per month and if there is any reduction in frequency or volume after high-dose albumin administration; (2) Twelve-month mortality or transplant. Secondary endpoints are: (1) Improvement of MELD score; (2) Cumulative diuretic dosage; (3) Development of hyponatremia or hyperkalemia as potential diuretic-induced side-effects; (4) Incidence of cirrhosis related complications (spontaneous bacterial peritonitis, other bacterial infections, renal impairment, hepatorenal syndrome, hepatic encephalopathy and gastrointestinal bleeding related to portal hypertension); (5) Quality of life; (6) Number and duration of hospital admissions; and (7) Treatment cost-effectiveness.

The research design is a prospective, parallel, randomized, open label clinical trial. The target trial population comprises of patients with advanced cirrhosis. Eligible patients will be randomized into either one of two categories: 1) the control group will receive the standard of care (SOC) including moderate sodium restriction and maximal daily tolerated doses of diuretics, and 2) the Intervention group will receive intravenous human albumin at a dose (1g/kg, with minimum dose of 50g and maximum dose of 100g) weekly plus SOC.

In both groups, when large-volume paracentesis is needed, the patient will receive human albumin in the dose of 6-8 g/L of ascites removed as SOC.

Inclusion Criteria:

1. Age > 18 years.
2. patients diagnosed with liver cirrhosis. Refractory ascites which is defined as ascites failing to resolve after maximum tolerable dose of diuretics, and usually require frequent paracentesis.

Exclusion Criteria:

1. Patients < 18y and patients with no history of liver cirrhosis
2. patients with refractory ascites but have trans-jagular intrahepatic portosystemic shunts (TIPS) with previous 3 months
3. Patients with ascites due to other causes, including cardiac, malignant Procedure Eligible patients will be identified by the PI and the research team. Participants will be approached to participate in the study. The research coordinator will fully explain the study procedures, and if the patient is willing to participate, he or she will sign the informed consent. After signing the informed consent, eligible patients will be randomly assigned into two groups: 1) the control arm will receive the standard of care (SOC), including moderate sodium restriction, maximal daily tolerated doses of diuretics, and post-paracentesis albumin, and 2) the intervention group will receive intravenous human albumin at a dose of (1g/kg), with a minimum dose of 50g and a maximum dose of 100g, plus SOC. patients will be randomly assigned (1:1) to either of these two groups.

In both groups, when large-volume paracentesis is needed, the participant will receive human albumin in the dose of 6-8 g/L of ascites removed.

No concomitant medications are withheld during the study. After enrollment, participants will be assessed by a physician monthly for up to one year or study interruption or liver transplant or death. In both groups with refractory ascites, most of the patient require weekly or biweekly monitoring and paracentesis. The investigators plan to approach the patients during these visits to get the consent and administer the extra albumin dose.

In each visit, ascites severity will be evaluated with hemodynamic status, weight, new symptoms, and diuretic dose. Each visit may last 15 minutes or more.

Patients who consent to the study will complete a self-administered questionnaire to assess health-related quality of life (using CLDQ, CLDQ-HCV and CLDQ- NASH Questionnaires). Each patient response will be coded to ensure privacy, and the coded data will be entered into a collection sheet with no protected health information (PHI) gathered during the survey. The investigators will give the questionnaire: at the time of enrollment and at the 6 and 12 month time points