Short-term Survival of Subjects With Acute-on-chronic Liver Failure After Plasma Exchange With Human Serum Albumin 5%

Inclusion Criteria:

• Male or female cirrhotic subjects between 18 and 79 years of age.

• Subjects with ACLF-1b, ACLF-2, or ACLF-3a detected either at admission or duringhospitalization (must be ACLF-1b, -2, or -3a within the Screening Period [a maximumof 10 days]).

• Willing and able to provide written informed consent or have an authorizedrepresentative able to provide written informed consent on behalf of the subject inaccordance with local law and institutional policy.

• In case of HE, informed consent will be provided by a relative or a legallyauthorized representative if the subject is considered incompetent to consent.

Exclusion Criteria:

• Subjects without ACLF.

• Subjects with ACLF-1a or ACLF-3b (See Table 2-1 for ACLF grades) after the ScreeningPeriod.

• Subjects fulfilling inclusion criteria that improve to no ACLF or to ACLF-1a orworsen to ACLF-3b during the Screening Period (between initial evaluation and timeof randomization).

• Subjects with ACLF for more than 10 days prior to randomization.

• Subjects with acute or subacute liver failure without underlying cirrhosis.

• Subjects with septic shock requiring use of norepinephrine (> 0.3 mcg/kg/min) orneed for a second vasopressor (including terlipressin).

• Subjects with active bacterial or fungal infection: who have received less than 24hof appropriate antibiotic treatment.

• Subjects with severe respiratory failure with PaO2/FiO2 ≤200.

• Subjects with active or recent bleeding (unless controlled for >48 hours).

• Subjects with severe thrombocytopenia (≤20×109/L) (based on local laboratoryassessment).

• Subjects with chronic renal failure and currently receiving hemodialysis.

• Evidence of current locally advanced or metastatic malignancy. Subjects withhepatocellular carcinoma within the Milan criteria (1 nodule ≤5 cm or 3 nodules ≤3cm [Appendix 5]), non-melanocytic skin cancer, and controlled breast or prostatecancer, can be included).

• Subjects with severe chronic heart failure (New York Heart Association [NYHA] classIII or IV).

• Subjects with severe pulmonary disease (Global Obstructive Lung Disease [GOLD] stageIII or IV).

• Subjects with severe myopathy as defined clinically.

• Subjects with a known infection with human immunodeficiency virus (HIV) or haveclinical signs and symptoms consistent with current HIV infection.

• Females who are pregnant, breastfeeding, or if of childbearing potential, unwillingto practice a highly effective method of contraception.

• Subjects with previous liver transplantation.

• Subjects receiving anti-platelet or anti-coagulant therapy (LMWH for DVT prophylaxisis allowed).

• Participation in another clinical study within at least 30 days prior to screening.

• Subjects with active drug addiction (exceptions: active alcoholism or marijuana).

• Subjects with a do-not-resuscitate order.

• In the opinion of the investigator, the subject may have compliance problems withthe protocol and the procedures of the protocol.

• Subjects with current infection of COVID19, those who are less than 14 days postrecovery or those who have clinical signs and symptoms consistent with COVID19infection.