This is a prospective, multicenter open-label single arm trial in which recipients of liver allograft will receive uniform immunosuppressive induction and maintenance regimens. Participants with end stage liver disease who meets the entry criteria will be consented and enrolled.

Participants receive Campath-1H and maintenance immunosuppression with tacrolimus therapy. After one year of tacrolimus therapy, an assessment of the immunologic status including blood gene expression and geno-race studies will be performed which will include studies on the liver graft biopsy. At this time, patients will be selected to undergo immunosuppressive withdrawal. This will be made on an individual basis with definitive inclusion and exclusion criteria.

The objectives of the study are to evaluate the safety and efficacy of immunosuppressive regimens comprising Campath-1H induction followed by maintenance immunosuppressive therapy with tacrolimus on allograft survival. However, secondary objectives will be to assess withdrawing tacrolimus after Campath-1H induction in an immune depletion and subsequent immune reconstitution. This study will evaluate whether a combination of anti-rejection medications (Campath-1H and tacrolimus) can prevent rejection and allow the body to develop tolerance to the transplanted liver.

Inclusion Criteria:

1. Male or female 18 years of age or older
2. Necessity for liver transplant
3. A negative pregnancy test at study entry for females of child-bearing potential
4. For participants with reproductive potential, agreement to use approved methods of birth control for the duration of their participation
5. Ability to provide informed consent
6. Availability of donor spleen

Exclusion Criteria:

1. Previous transplant
2. Multiorgan transplant
3. Living donor transplant.
4. Donor liver from a donor positive for antibody against hepatitis B core antigen
5. Donor liver from a donor positive for antibody against hepatitis C
6. Donor liver from a non-heart-beating donor
7. Liver failure due to autoimmune disease, such as autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cirrhosis
8. Hepatitis B infection as defined by the presence of HbSAg or active treatment for hepatitis B
9. Hepatitis C as defined by the presence of antibody against hepatitis C.
10. Stage III or higher hepatocellular cancer based on pretransplant imaging
11. History of malignancy except hepatocellular cancer, or adequately treated in situ cervical carcinoma, adequately treated basal or squamous cell carcinoma of skin, or other malignancy which is judged to have a 5-year risk of recurrence of < 5%
12. Active systemic infection at the time of transplantation
13. Clinically significant chronic renal disease
14. Clinically significant cardiovascular or cerebrovascular disease
15. Infection with human immunodeficiency virus
16. Any investigational drug received within 6 weeks of study entry
17. Hypersensitivity to Campath-1H or tacrolimus
18. Unwillingness or inability to comply with study requirements (Immune Tolerance Network CONFIDENTIAL iv Protocol ITN024ST Immunosuppression with Campath-1H Version 3.0 June 28, 2005 and Tacrolimus in Liver Transplantation)
19. Inability to give appropriate informed consent (e.g., hepatic encephalopathy stage 2 or higher at time of screening consent)
20. Positive PPD without evidence of prior treatment or administration of BCG