Mesenchymal stem cells (MSC) has been reported to improved outcomes of acute-on-chronic liver failure(ACLF). More randomization controlled studies are needed to confirm the effect of MSC treatment for ACLF. This study aimed to investigate the efficacy of mesenchymal stem cells in ACLF patients. This study is an double-blind multicenter randomized and placebo-controlled study. Patients with with ACLF will be randomly assigned to receive MSC treatment (experimental) or standard medical treatment (control). Three times of MSC infusion (0.1-1x10E6cells/kg body weight) via peripheral vein will be given to the experimental group (once per week). The primary outcome is 12 week mortality. Secondary outcomes are clinical remission rate and changes of liver function indices and liver function scores.

Inclusion Criteria:

• Age between 18-70 years old
• Meeting the criteria of ACLF defined as: 1. definitive chronic liver diseases, acute decompensation within 4 weeks; 2. Significant GI symptom as such fatigue, jaundice,; 3. total bilirubin (TBIL) ≥170 µmo1/L or daily increase of TBIL ≥17.1 µmo1/L; 4. PTA≤40% or INR≥ 1.5; 5. Decompensation of liver functions such as ascites or hepatoencephalopathy;
• MELD score between 17-30. (MELD(i) = 0.957 × ln(Cr) + 0.378 × ln(bilirubin) + 1.120 × ln(INR) + 0.643)
• Chronic liver disease with definitive etiology such as viral hepatitis, alcohol liver disease, drug induced liver injury or autoimmune liver diseases
• Informed consent

Exclusion Criteria:

• Sever complications with 30 days ( GI bleeding, severe infection)；

  --liver cancer or other malignancies

• patients on liver transplantation list

• patients with uncontrolled infections

• severe renal failure

• Severe chronic obstructive pulmonary disease COPD (GOLD III-IV)

• Extrahepatic cholanstasis patients due to biliary obstruction.

• HIV infection

• Pregnant or breast-feeding females.

• Enrolled in other clinical trials with 3 months

• other conditions considered inappropriate for the study

Study protocol, statistical analysis processes and clinical data of individual participants will be shared.

within 12 months after the study completion and before publications of the findings.

Randomization will be blinded to participant, care provider, investigator and outcome assessors.