This open-label, proof-of-principle two center cohort study will evaluate the ability of autologous hematopoietic stem cell transplantation to induce tolerance in recipients of deceased or live donor liver transplants (ASCOTT). A maximum of 10 participants will be entered at a minimum of 3 months post liver transplant. The participants will undergo autologous hematopoietic stem cell transplants (HSCT) to "re-educate" their immune systems to accept the graft without the need for long term immunosuppression (tolerance).

Although short-term results for liver transplantation are excellent, the need for immunosuppression limits quality of life and long-term survival.

Investigators plan to examine the utility and safety of autologous hematopoietic stem cell transplantation (HSCT) to allow withdrawal of immunosuppression in 10 liver transplant recipients who are at a high risk of developing recurrent liver damage from repeated bouts of rejection, or recurrent disease or who have a high likelihood of developing serious medical complications from complications of immune suppression.

Hematopoietic stem cells will be mobilized, purified and cryopreserved. Following a chemotherapy and Anti-thymocyte Globulin (ATG) based-regimen for immune ablation, the purified stem cells will be thawed and infused back into participants (autologous hematopoietic stem cell transplant - HSCT). Participants will be converted to everolimus, a mammalian target of rapamycin inhibitor (mTORi), which will be continued for 6 months and then withdrawn based on histologic evidence of graft acceptance.

Participants will be followed closely for a total of 24 months for any biochemical and histologic evidence of tolerance or rejection. Re-vaccination to common viral and bacterial antigens will be undertaken as required using a standard protocol for recipients of a hematopoietic stem cell transplant (HSCT).

Inclusion Criteria:

1. Participants must be 18 years of age or older.
2. Participants must be a minimum of 6 months post-transplant;
3. Participants are recipients of a hepatic allograft for alcohol induced liver disease; or a genetic form of liver disease such as hemochromatosis or Wilson's disease; or an autoimmune liver disease including sclerosing cholangitis, autoimmune hepatitis, and/or primary biliary cirrhosis.
4. Participants have a complication of transplantation that might be ameliorated by HSCT and/or withdrawal of immunosuppression such as: evidence of recurrent autoimmune disease in the graft; repeated episodes (minimum of 2) of acute cellular rejection; and/ or development of adverse events related to immune suppression which have not been well managed by conventional methods including drug dose reduction or substitution of other medications. Examples include progression of renal dysfunction, repeated infections, neurologic complications, cardiovascular complications, or post-transplant lymphoproliferative disease (PTLD) that has been in remission for at least 12 months. These complications must be deemed serious enough to warrant inclusion in the study by the investigator.

Exclusion Criteria:

1. Participants < 18 yr.
2. Participants with cardiac, renal, pulmonary, hepatic, or other organ impairment that would limit their ability to receive dose intensive chemotherapy;
3. Participants with any active or chronic infection. Participants with previous reactivation of Epstein-Barr virus, cytomegalovirus , BK, human herpesvirus 6 or varicella-zoster virus would be considered eligible if the virus has returned to a latent state;
4. Participants who are seropositive for HIV1, HIV2, Hepatitis B Surface Antigen, and Hepatitis C;
5. Participants with a previous history of a malignancy other than squamous or basal cell carcinoma of the skin, or post-transplant lymphoproliferative disease (PTLD);
6. Participants whose life expectancy is severely limited by another co-morbid illness;
7. Participants with evidence of myelodysplasia, other non-autoimmune cytopenia, or an inherited immunodeficiency state;
8. Pregnancy or Participants who are unwilling to practice two active forms of contraception during the time of chemotherapy administration. Participants must be willing to commit to not becoming pregnant from enrollment in the study until 2 years following their HSCT.
9. Participants unable to comply with the medical treatment specified in the protocol;
10. Participants unable to give written informed consent in accordance with research ethics board guidelines.