Personalized Long-term Human Albumin Treatment in Patients With Decompensated Cirrhosis and Ascites

A Randomized Multicentre, Double-Blinded and Placebo-Controlled, Trial of Human Albumin in the Treatment of Decompensated Cirrhosis Guided by the MICROB-PREDICT Biomarker

There will exist two levels of masking in the current trial. Masking of biostratification outcome (high expected effect of human albumin or low expected effect of human albumin): Participant, Investigator and Outcome Assessor Masking of treatment assignment (human albumin 20% or saline 0.9%): Participant and Outcome Assessor

A liver-related clinical outcome is defined as variceal bleeding, ascites, spontaneous bacterial peritonitis, infection requiring hospitalization, acute kidney injury (>=1B), overt hepatic encephalopathy, TIPS insertion, liver transplantation or death.

A liver-related clinical outcome is defined as variceal bleeding, ascites, spontaneous bacterial peritonitis, infection requiring hospitalization, acute kidney injury (>=1B), overt hepatic encephalopathy, TIPS insertion, liver transplantation or death. Time to any of these outcomes are defined as the time from trial inclusion until 1) the date of diagnosis of any of the complications, 2) the date of the procedure (TIPS or liver transplantation) or date of death.

Quality of life for participants, as measured by Short Form 36 (SF-36), ranging from 0 to 100 with a score of 0 equal to maximum disability and score of 100 no disability.

Quality of life for participants, as measured by the Chronic Liver Disease Questionnaire (CLDQ), consisting of 29 items within 7 domains. Response on a Likert scale ranging from 1 (most impairment) to 7 (least impairment). Total score by adding score for each item and divide by number of items (29).

Quality of life for participants, as measured by the EuroQoL-5 Domain, 5 levels (EQ-5D-5L). Consist of 5 domains with 5 levels where the lowest level (1) is the worst imaginable health and highest level (5) is the best imaginable health.

Change in concentration of the panel of predictive circulating metabolites compared to metabolite levels in other body fluid compartments (blood, urin, stool and saliva)

According to the Kidney Disease: Improving Global Outcomes (KDIGO) definition ranging from stage 1A to 3 where a higher stage is worse.

Inclusion Criteria: Decompensated liver cirrhosis defined as Child-Pugh score 7-12 Clinical and/or ultrasound evidenced ascites Age ≥ 18 years At least five days since resolution of a decompensation event or any condition requiring hospitalisation Exclusion Criteria: Patients with acute or subacute liver failure without underlying cirrhosis Patients with cirrhosis who develop decompensation in the postoperative period following partial hepatectomy Refractory ascites as defined by the International Ascites Club Existing TIPS Portal vein thrombosis Severe alcoholic hepatitis (Glasgow Alcoholic Hepatitis Score > 11) Hepatic encephalopathy grade III-IV Current, planned or previous treatment with direct antiviral agents for hepatitis C virus (HCV) in the last six months Contraindications for human albumin infusion (pulmonary oedema, hypersensitivity etc.) Evidence of current malignancy except for non-melanocytic skin cancer and hepatocellular carcinoma within Barcelona Clinic Liver Cancer (BCLC)-0 or BCLC-A Presence or history of severe extra-hepatic diseases (e.g.,chronic renal failure requiring hemodialysis, severe heart disease (NYHA > II); severe chronic pulmonary disease (GOLD Score ≥ C), severe neurological and psychiatric disorders, pulmonary arterial hypertension) HIV positive or other condition associated with and/or requiring immunosuppression Previous liver or other transplantation Pregnancy Breastfeeding Patients who decline to participate, patients who cannot provide prior written informed consent due to other causes than hepatic encephalopathy or patients with hepatic encephalopathy who cannot provide prior written informed consent and when there is documented evidence that the patient has no legal surrogate decision maker or sufficient ability to provide delayed informed consent Physician's denial (investigator considers that the patient will not adhere to the study protocol scheduled, e.g. in case of heavy drinking) Participation in another study within 3 months prior to screening