This is an interventional, single arm, multicenter, phase I/IIa clinical trial. The study objective is to investigate the efficacy and safety of three i.v. doses of the investigational medicinal product (IMP) allo-APZ2-ACLF for the treatment of acute-on-chronic liver failure (ACLF). The allogeneic IMP allo-APZ2-ACLF contains skin-derived ABCB5-positive mesenchymal stem cells isolated from skin tissue of healthy donors and stored in a donor cell bank.
Inclusion Criteria: 1. Male or female patients, aged 20 to 75 years; 2. Diagnosed ACLF of grade 2 or 3 according to EASL-CLIF definition; 3. Patients are not eligible for liver transplant (confirmed by transplantation board); 4. Histology result of liver biopsy not older than 4 weeks before screening; 5. Women of childbearing potential must have a negative blood pregnancy test at screening; 6. Women of childbearing potential and fertile men, and their partners must be willing to use highly effective contraceptive methods during the course of the clinical trial; 7. Written informed consent from patient, legal or authorized representative or a confirmation of justification of trial participation by an independent medical consultant. In case of confirmation by the independent medical consultant, a deferred informed consent from patient, legal or authorized representative has to be given. Exclusion Criteria: 1. Patients without cirrhosis; 2. Patients with ACLF grade 1 according to EASL-CLIF definition; 3. Patient with septic shock; 4. Patients with known hepatopulmonal syndrome (HPS); 5. Patients with known pulmonary embolism that needs anticoagulative treatment; 6. Patients with pre-existing lung disease with necessity of respiratory support; 7. Active malignancy or history of malignancy within 5 years prior to trial entry; 8. Known infection with human immunodeficiency virus (HIV˗1, HIV-2); 9. Any known allergies to components of the IMP; 10. Current or previous (within 30 days of enrolment) treatment with another IMP, or participation and/or under follow-up in another clinical trial; 11. Patients anticipated to be unwilling or unable to comply with the requirements of the protocol; 12. Evidence of any other medical conditions (such as psychiatric illness, physical examination, or laboratory findings) that may interfere with the planned treatment, affect the patient's compliance, or place the patient at high risk of complications related to the treatment; 13. Pregnant or nursing women; 14. Employees of the sponsor, or employees or relatives of the investigator.