Human Umbilical Cord-mesenchymal Stem Cells Via Different Transplantation Routes in ESLD

Thirty-two participants with end-stage liver disease admitted to the Department of Gastroenterology of the General Hospital of Northern Theater Command are expected to be enrolled over a period of 6 months. They will be randomly assigned to peripheral vein infusion and hepatic arterial infusion of human umbilical cord mesenchymal stem cell groups. The investigators will observe alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, albumin, prothrombin time, international normalized ratio, model for end-stage liver disease score, and Child-Pugh score at weeks 4, 12, and 24 post-infusion.

• Infusion of umbilical cord-mesenchymal stem cells through peripheral veins (Other): Umbilical cord-mesenchymal stem cells injected through peripheral veins
• Infusion of umbilical cord-mesenchymal stem cells through hepatic artery (Other): Umbilical cord-mesenchymal stem cells injected through hepatic artery

Primary outcomes

• Survival rate [24 weeks]: Number of subjects surviving after 24 weeks

Secondary outcomes

• Changes in Model for End-Stage Liver Disease (MELD) score [4, 12, and 24 weeks]: The Model for End-Stage Liver Disease (MELD) score ranges from 6 to 40, with higher values indicating more severe liver dysfunction and an increased risk of mortality.
• Changes in Child-Pugh score [4, 12, and 24 weeks]: The Child-Pugh score is categorized into class A (5-6 points), class B (7-9 points), and class C (≥10 points), reflecting progressive liver disease severity. Higher Child-Pugh scores are associated not only with increased mortality risk but also with a significantly higher incidence of complications, such as gastrointestinal bleeding and infections.
• Incidence of hepatic decompensation events [4, 12, and 24 weeks]: Number of patients who developed gastrointestinal bleeding, ascites, and hepatic encephalopathy

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

1. 18-80 years old

   \-
2. End-stage liver disease

   \-
3. Signed informed consent

Exclusion Criteria:

1. Tumours of the liver or other organs

   \-
2. Liver transplantation recipients

   \-
3. Acute myocardial infarction, acute heart failure, type I and type II respiratory failure, pulmonary embolism, acute cerebral infarction, acute cerebral haemorrhage and other serious cardiopulmonary diseases

   \-
4. Other diseases that may seriously affect the survival

   \-
5. Human immunodeficiency syndrome

   \-
6. Interferon or glucocorticoid therapy within 1 year

   \-
7. Treated for mental illness

   \-
8. Participation in other clinical trials within 30 days

   \-
9. Pregnant or breastfeeding subjects

   \-
10. Allergic asthma, allergic urticaria, eczema, or a history of multiple drug and food allergies

    \-
11. Severe coagulopathy or renal dysfunction

    \-
12. Other circumstances that are unsuitable for participation in this study

• Results publication: Lyra AC, Soares MB, da Silva LF, Braga EL, Oliveira SA, Fortes MF, Silva AG, Brustolim D, Genser B, Dos Santos RR, Lyra LG. Infusion of autologous bone marrow mononuclear cells through hepatic artery results in a short-term improvement of liver function in patients with chronic liver disease: a pilot randomized controlled study. Eur J Gastroenterol Hepatol. 2010 Jan;22(1):33-42. doi: 10.1097/MEG.0b013e32832eb69a. PMID 19654548
• Results publication: Zhou GP, Jiang YZ, Sun LY, Zhu ZJ. Therapeutic effect and safety of stem cell therapy for chronic liver disease: a systematic review and meta-analysis of randomized controlled trials. Stem Cell Res Ther. 2020 Sep 25;11(1):419. doi: 10.1186/s13287-020-01935-w. PMID 32977828

• Xingshun Qi, MD, Study director, The General Hospital of Northern Theater Command Study Director
• Liyan Dong, MM, Principal investigator, The General Hospital of Northern Theater Command Study Director