Umbilical Cord Mesenchymal Stem Cells for Patients With Autoimmune Hepatitis
Umbilical Cord Mesenchymal Stem Cells for Patients With Autoimmune Hepatitis
Autoimmune hepatitis (AIH) is characterized by chronic inflammation of the liver, interface
 hepatitis, hypergammaglobulinemia, and the presence of autoantibodies. Disease presentation
 is varied but typically is based on characteristic aminotransferase elevations, histological
 abnormalities, elevated levels of serum globulins, and the presence of one or more
 autoantibodies. Two types of juvenile AIH have been identified according to seropositivity
 for smooth muscle and /or antinuclear antibody (AIH type 1) or liver kidney microsomal
 antibody (AIH type 2). Standard therapy in clinic consists of a combination of
 corticosteroids and azathioprine, which displays the efficacy in 80% of patients. However, 7%
 of patients deteriorate despite compliance with the standard corticosteroid regiments
 (treatment failure),13% of patients improve but not to a degree that satisfies remission
 criteria (incomplete response), 13% of patients develop serious drug-induced complications,
 and 50%-86% of patients will relapse after drug withdrawal. These serious drawbacks
 counterbalance the benefits of conventional therapy, and they are compelling reasons to
 refine current treatment strategies and pursue alternative therapies. UC-MSC has been the
 application for the treatment of several severe autoimmune diseases, such as immune
 thrombocytopenia, systemic lupus erythematosus, and therapy-resistant rheumatoid arthritis.
 In this study, the safety and efficacy of UC-MSC transplantation for AIH patients will be
 evaluated.
Autoimmune hepatitis (AIH) is an immune-mediated necroinflammatory disease of the liver
 characterized by elevation of IgG, presence of characteristic autoantibodies, and
 histological feature of interface hepatitis. Standard therapy consists of a combination of
 corticosteroids and azathioprine, which is efficacious in 80% of patients. However, current
 treatment strategies are complicated by frequent relapse after drug withdrawal, medication
 intolerance, and refractory disease. Alternative medical therapy may be need for AIH.

 The potential for stem cells to differentiate into hepatocytes cells was recently confirmed.
 In particular, bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been
 applicated in the clinic for treat several human disease such as GVHD, cardiac injury and
 brain injury, and displayed good tolerance and efficiency. Recently, umbilical cord-derived
 MSCs (UC-MSC) has also been used to treat severe autoimmune diseases, such as immune
 thrombocytopenia, systemic lupus erythematosus, and therapy-resistant rheumatoid arthritis.

 The purpose of this study is to learn whether and how UC-MSC can improve the disease
 condition in patients with autoimmune hepatitis (AIH). This study will also look at how well
 UC-MSC is tolerated and its safety in AIH patients

 Participants in the study will be randomly assigned to one of two treatment arms:

 Arm A: Participants will receive 12 weeks of UC-MSC treatment plus conventional treatment
 (combination of corticosteroids and azathioprine) Arm B: Participants will receive 12 weeks
 of placebo plus conventional treatment. (combination of corticosteroids and azathioprine)
 UC-MSC will be prepared according to standard procedures and is collected in plastic bags
 containing anticoagulant. UC-MSCs are given via i.v. under sonography monitoring. After cell
 therapy, patients are followed up at week 12, 24, 36, 48, 72, 96. The evaluation of some
 clinical parameters such as the level of serum alanine aminotransferase (ALT), aspartate
 aminotransferase (AST), γ-globulin, total bilirubin (TB), prothrombin time (PT), albumin
 (ALB), prealbumin (PA) and IgG, are detected at these time points. MELD score, Liver
 histology, treatment side effects, relapse rate and clinical symptoms were also observed
 simultaneously.
Inclusion Criteria:

 1. Written informed consent

 2. Autoimmune hepatitis (according to the criteria defined by the international
 autoimmune hepatitis Group ,Hepatology, 2008;48:169-176)

 3. Negative pregnancy test (female patients in fertile age)

 Exclusion Criteria:

 1. Hepatocellular carcinoma or other Malignancies

 2. Pregnant or lactating women

 3. Viral Hepatitis ( HAV,HBV,HCV, et al )

 4. Vital organs failure (Cardiac, Renal or Respiratory, et al)

 5. Sepsis

 6. Active thrombosis in the portal or hepatic veins