Liver Failure, Acute on Chronic
Conditions
Keywords
mesenchymal stem cell
Brief summary
Safety and Efficacy of Mesenchymal Stem Cell Transplantation for Acute-on-Chronic Liver Failure
Detailed description
Acute-on-chronic liver failure (ACLF) which occurs in patients with chronic liver disease, is a serious live-threatening disease. Currently, the clinical management, such as liver protection, anti-virus medicine, and artificial liver support, has not significantly improve the outcomes, the mortality still remains over 50%. Liver transplantation is the only effective treatment of ACLF, but this therapy is limited by the shortage of donor organs, potential surgical complications, immunological rejection and high medical costs. Mesenchymal stem cell (MSC) is one of adult stem cells, which has been suggested to play a role in amelioration of liver disease, such as: trans-differentiation of MSCs into hepatocytes, immunomodulation, inhibition of fibrosis development, protective effects on hepatic cell and restoration of hepatic cell proliferation capacity.
Interventions
BIOLOGICALMesenchymal Stem Cell
Mesenchymal stem cell transplantation via peripheral vein: 1.0-10x10\^5 MSCs/kg body weight administered via peripheral vein at week 0, 1, 2, 3 weeks
Sponsors
Tianjin Nankai Hospital
Tianjin Weikai Bioeng., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
both participants and the study team are unblinded to the treatment allocation
Eligibility
Sex/Gender
ALL
Age
16 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Informed consent 2. Meeting the definition of ACLF: patients with previously diagnosed or undiagnosed chronic liver disease acute decompensated within 4 weeks; significant GI symptom as such fatigue, jaundice; serum total bilirubin \[TBil\] ≥10 X the upper limit of normal; coagulopathy (international normalized ratio \[INR\] ≥1.5 or prothrombin activity \[PTA\] \<40%); complicated within 4 weeks by ascites and/or encephalopathy as determined by physical examination. 3. Model for End-Stage Liver Disease (MELD) scores ranging 17-30, (MELD(i) = 0.957 × ln(Cr) + 0.378 × ln(bilirubin) + 1.120 × ln(INR) + 0.643); 4. Chronic liver disease with definitive etiology such as viral hepatitis, alcohol liver disease, drug induced liver injury or autoimmune liver diseases 5. Body weight ≥50kg
Exclusion criteria
1. Serious complications in the previous 2 months (e.g., gastrointestinal bleeding: hemoglobin below 90g/L, serious infection such as sepsis, ascites ultrafiltration, and/or dialysis); 2. Malignant jaundice induced by obstructive jaundice or hemolytic jaundice; 3. Hepatocellular carcinoma (HCC) diagnosed by radiologic imaging and/or alpha fetoprotein (AFP); 4. Tumor diagnosed by ultrasound, CT, MR examination; 5. Moderate or severe chronic heart failure (NYHA III-IV), renal replacement therapy, severe chronic pulmonary disease (GOLD III-IV) 6. Extrahepatic cholestasis 7. Hepatic, portal and splenic vein thrombosis diagnosed by doppler ultrasound 8. Artificial liver support 9. Previous liver transplantation 10. Drug abuse in the past 5 years; 11. Mental disorders and/or has a family history of mental disorder. 12. HIV infection 13. Pregnant or breast-feeding females 14. Highly allergic 15. Patients can not cooperate or mobility 16. Enrolled in other clinical trials with 3 months 17. Patients who can not provide prior informed consent or refusal to participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| survival rate | 72 weeks after treatment | Number of participants alive |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| White blood cell | Week 1, 2, 4, 8, 12, 24, 36, 48 | Change of white blood cell count |
| Platelet | Week 1, 2, 4, 8, 12, 24, 36, 48 | Change of platelet count |
| Hemoglobin | Week 1, 2, 4, 8, 12, 24, 36, 48 | Change of hemoglobin level |
| Creatinine | Week 1, 2, 4, 8, 12, 24, 36, 48 | Change of creatinine level as a surrogate marker of liver function |
| ALT | Week 1, 2, 4, 8, 12, 24, 36, 48 | Change of alanine aminotransferase (ALT) level as a marker of liver function |
| ALB | Week 1, 2, 4, 8, 12, 24, 36, 48 | Change of albumin (ALB) level as a maker of liver function |
| Adverse reactions | Week 1, 2, 4, 8, 12, 24, 36, 48 | Number of participants with adverse reactions (e.g. fever, rash, and diarrhea ) |
| INRs | Week 1, 2, 4, 8, 12, 24, 36, 48 | Change of international normalized ratio (INRs) level as a marker of liver function |
| AFP | Week 1, 2, 4, 8, 12, 24, 36, 48 | Change of alpha fetoprotein (AFP) level as a marker of liver function |
| MELD scores | Week 1, 2, 4, 8, 12, 24, 36, 48 | Model for End-Stage Liver Disease (MELD) score for assessing the severity of chronic liver disease is measured as absolute change to baseline score |
| Tumor formation | Week 1, 2, 4, 8, 12, 24, 36, 48 | Number of participants with hepatocellular carcinoma or extrahepatic malignant tumors |
| Liver failure-associated serious complications | Week 1, 2, 4, 8, 12, 24, 36, 48 | Number of participants with liver failure-associated serious complications, such as infections, encephalopathy, gastrointestinal bleeding and HRS |
| TBil | Week 1, 2, 4, 8, 12, 24, 36, 48 | Change of total Bilirubin (TBil) level as a marker of liver function |
Countries
China
Contacts
Primary ContactXiuli Cong, MD, PhD
Outcome results
None listed