Patient enrollment

Inclusion Criteria:

• Age > 55 years old at the time of evaluation
• An established diagnosis of PBC, i.e. presence of all three diagnostic criteria, detectable serum AMA at titer >1:40, elevated alkaline phosphatase levels for > 6 months, and compatible liver histology
• Incomplete response to UDCA at 13-15 mg/kg/day (Incomplete response is defined as elevated serum alkaline phosphatase (>2X upper normal value) after 12 months of UDCA therapy, as defined by Angulo and colleagues).

And any of the following

• Pruritus unresponsive to medical therapy
• Liver disease with more than 50% probability of dying or needing a LTx in the following 36 months according to the Mayo survival model(equivalent to a Mayo score higher than 6.78 (The Mayo survival model is a validated survival instrument based on age, bilirubin PT, and edema that does not require a liver biopsy).

Exclusion Criteria:

• Poor performance status (ECOG > 2) at the time of entry

  2.Serum bilirubin > 4.0 mg/dl

  3.Significant end organ damage such as:

  1. LVEF < 40% or deterioration of LVEF during exercise test on MUGA or echocardiogram
  2. Untreated life-threatening arrhythmia
  3. Active ischemic heart disease or heart failure
  4. End-stage lung disease characterized by DLCOadj < 45% of predicted value

  5. Serum creatinine > 2.0 mg/dl

     4.HIV positive

     5.Uncontrolled diabetes mellitus, or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive treatment

     6.Prior history of malignancy except localized basal cell or squamous skin cancer; Other malignancies for which the patient is judged to be cured by local surgical therapy, such as (but not limited to) head and neck cancer, or stage I or II breast cancer will be considered on an individual basis

     7.Positive pregnancy test, inability or unable to pursue effective means of birth control, failure to willingly accept or comprehend irreversible sterility as a side effect of therapy

     8.Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible

     9.Inability to give informed consent

     10.Major hematological abnormalities such as platelet count < 100,000/ul or ANC < 1000/ul

     11.GI bleed from portal hypertension

     12.Portal HTN documented by transvenous portal vein wedge pressure greater than 20 cm H20

     13.Ascites that is non-responsive to full-dose diuretics and human albumin infusion

     14.Systemic sclerosis

     15.AMA positive donor

     16.HCV PCR positive or HBSAg positive donor

     17.Failure to collect less than 2.0 x 106 CD34 cells/kg from a matched sibling

     18.Patient on liver transplant list

     Donor enrollment

     Inclusion Criteria:

     1. Donor must be a HLA identical sibling or HLA matched cord blood donor.
     2. If multiple HLA matched donors are available, preference will be given to same sex, same CMV status, or in the case of cord blood higher nucleated cell count.
     3. AMA negative
     4. If no HLA matched sibling is available, donor may be HLA matched cord blood. The minimum number of cord blood nucleated cells available must be more than 2X107/kg. To achieve this number of nucleated cells, two units of HLA matched cord blood may be utilized (Wagner JE Blood 2005 Feb 1; 105(3): 1343-7)

     Exclusion criteria:

     1. Physiologic age > 50 years old or <18 years old (except cord blood units)
     2. HIV positive
     3. Active ischemic heart disease or heart failure
     4. Acute or chronic active hepatitis
     5. Uncontrolled diabetes mellitus or any other illness that in the opinion of the investigators would jeopardize the ability of the donor to tolerate stem cell collection
     6. Prior history of malignancy except localized basal cell or squamous skin cancer; Other malignancies for which the patient is judged to be cured by local surgical therapy, such as (but not limited to) head and neck cancer, or stage I or II breast cancer will be considered on an individual basis
     7. Positive pregnancy test
     8. Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
     9. Major hematological abnormalities such as platelet count less than 100,000/ul, ANC less than 1000/ul