Anti-CD25 and Tacrolimus Therapy May Not Prevent Early Primary Biliary Cirrhosis Recurrence After Liver Transplantation: Two Case Reports B. Foroncewicz, K. Mucha, L. Paczek, U. Oldakowska-Jedynak, B. Go ´ rnicka, K. Zieniewicz, P. Nyckowski, and M. Krawczyk ABSTRACT Primary biliary cirrhosis (PBC) is an immune-mediated disorder of unknown cause characterized by progressive destruction of intrahepatic bile ducts and the presence of antimitochondrial antibodies. There is no known cure for PBC, and treatment generally includes various combinations of ursodeoxycholic acid and immunosuppressive agents. However, in most patients with end-stage PBC, liver transplantation offers a good quality of life. Recurrent PBC after transplantation is controversial, because most patients with suspected recurrent disease are asymptomatic. Antimitochondrial antibodies frequently persist and do not correlate with disease recurrence. However, most studies support disease recur- rence within the graft. The effects of immunosuppression may modify or delay disease expression within the graft. If PBC recurs, intermediate-term patient and graft survivals are excellent, but the long-term outcome remains unknown. Many immunosuppressive agents have been studied with regard to their anti-recurrence properties; however, no standard therapy has been established for this group of patients. In this study we present two patients transplanted for PBC who displayed early recurrence of disease confirmed by liver biopsy and elevated serum AMA. Both individuals received the same immunosup- pressive regimen. The data suggest that two doses of daclizumab and tacrolimus monotherapy in the early posttransplant period is insufficient to prevent recurrence of PBC. Addition of glucocorticoids may have beneficial effects in these patients. INTRODUCTION P RIMARY BILIARY cirrhosis (PBC) is an immune- mediated disorder of unknown etiology characterized by progressive destruction of intrahepatic bile ducts and the presence of antimitochondrial antibodies (AMA). The dis- ease, which has a strong female preponderance (10:1), is commonly associated with other autoimmune disorders including sicca complex, CREST syndrome, rheumatoid arthritis, thyroiditis, pernicious anemia, and renal tubular acidosis. 1 In approximately 90% of patients with PBC the serum contains antibodies against a lipoprotein component of the inner mitochondrial membrane. 2 Several agents have been used to treat patients with confirmed PBC. Ursodeoxycholic acid (UDCA), a hydro- philic bile acid seems to slow the progression of disease, possibly by reducing the concentration of toxic bile acids in the hepatic pool. However, no antifibrotic effect of the UDCA has been observed. Cyclosporine (CsA) had shown some early promise, but its long-term use has yielded only moderate benefit compared with the side effects. 3 Other immunosuppressive agents including azathioprine, metho- trexate, chlorambucil, and prednisone have met with mod- est success. Interferon-gamma may have immunopatho- genic importance in PBC. However, neither UDCA nor From the Department of Immunology, Transplant Medicine, and Internal Diseases (B.F., K.M., L.P.), Transplantation Institute, the Department of Pathology (B.G.), and the Department of General, Transplantation, and Liver Surgery (K.Z., P.N., M.K.), Medical University of Warsaw, Warsaw, Poland. Address reprint requests to B. Foroncewicz, Department of Immunology, Transplant Medicine, and Internal Diseases, Med- ical University of Warsaw, Nowogrodzka 59 Str., PL02-006 Warsaw, Poland. 0041-1345/03/$–see front matter © 2003 by Elsevier Inc. All rights reserved. doi:10.1016/S0041-1345(03)00835-2 360 Park Avenue South, New York, NY 10010-1710 2310 Transplantation Proceedings, 35, 2310 –2312 (2003)