WEANING OF IMMUNOSUPPRESSION IN LONG-TERM LIVER-TRANSPLANT RECIPIENTS

Seventy-two long-surviving liver transplant recipients were evaluated prospectively, including a baseline allograft biopsy for weaning off o f immunosuppression. Thirteen were removed from candidacy because of c hronic rejection (n = 4), hepatitis (n = 2), patient anxiety (n = 5), or lack of cooperation by the local physician (n = 2). The other 59, a ged 12-68 years, had stepwise drug weaning with weekly or biweekly mon itoring of liver function tests. Their original diagnoses were PBC (n = 9), HCC (n = 1), Wilson's disease (n = 4), hepatitides (n = 15), Lae nnec's cirrhosis (n = 1), biliary atresia (n = 16), cystic fibrosis (n = 1), hemochromatosis (n = 1), hepatic trauma (n = 1), alpha-1-antitr ypsin deficiency (n = 9), and secondary biliary cirrhosis (n = 1). Mos t of the patients had complications of long-term immunosuppression, of which the most significant were renal dysfunction (n = 8), squamous c ell carcinoma (n = 2) or verruca vulgaris of skin (n = 9), osteoporosi s and/or arthritis (n = 12), obesity (n = 3), hypertension (n = 11), a nd opportunistic infections (n = 2). When azathioprine was a third dru g, it was stopped first. Otherwise, weaning began with prednisone, usi ng the results of corticotropin stimulation testing as a guide. If adr enal insufficiency was diagnosed, patients reduced to < 5 mg/day predn isone were considered off of steroids. The baseline agents (azathiopri ne, cyclosporine, or FK506) were then gradually reduced in monthly dec rements. Complete weaning was accomplished in 16 patients (27.1%) with 3-19 months drug-free follow-up, is progressing in 28 (47.4%), and fa iled in 15 (25.4%) without graft losses or demonstrable loss of graft function from the rejections. This and our previous experience with se lf-weaned and other patients off of immunosuppression indicate that a significant percentage of appropriately selected long-surviving liver recipients can unknowingly achieve drug-free graft acceptance. Such at tempts should not be contemplated until 5-10 years posttransplantation and then only with careful case selection, close monitoring, and prom pt reinstitution of immunosuppression when necessary.