Safety and Efficacy of Mesenchymal Stem Cell Transplantation for Acute-on-Chronic Liver Failure

Tianjin Weikai Bioeng

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Liver Failure, Acute on Chronic

Treatments: Biological: Mesenchymal Stem Cell

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03863002

Tianjin Weikai Bioeng., Ltd

Details and patient eligibility

About

Safety and Efficacy of Mesenchymal Stem Cell Transplantation for Acute-on-Chronic Liver Failure

Full 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.

Enrollment: 45 estimated patients

Sex: All

Ages: 16 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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45 participants in 2 patient groups

Standard Medical Treatment

No Intervention group

Description:

Standard Medical Treatment (SMT): All patients received SMT, including nutritional supplementation; administration of human serum albumin (serum albumin \<30 g/L), fresh frozen plasma (200-400 mL/day until the INR was \<1.5), S-adenosylmethionine (1.0 g/day); or anti-virus treatment for hepatic viruses-related cases, and appropriate treatment for complications such as infections (including of the respiratory tract, urinary tract, biliary tract, and digestive tract and spontaneous peritonitis), encephalopathy, gastrointestinal bleeding, and hepatorenal syndrome \[HRS\]).

Mesenchymal Stem Cell

Experimental group

Description:

Mesenchymal Stem Cell (MSC): The MSC group received infusions of 1.0 to 10x10\^5cells/kg MSCs through the peripheral vein once a week for 4 weeks, in addition to SMT.

Treatment:

Biological: Mesenchymal Stem Cell