WEANING OF IMMUNOSUPPRESSION IN LIVER-TRANSPLANT RECIPIENTS

Immunosuppression has been sporadically discontinued by noncompliant l iver allograft recipients for whom an additional 4 1/2 years of follow -up is provided. These anecdotal observations prompted a previously re ported prospective drug withdrawal program in 59 liver recipients. Thi s prospective series has been increased to 95 patients whose weaning w as begun between June 1992 and March 1996, 8.4+/-4.4 (SD) years after liver replacement. A further 4 1/2 years follow-up was obtained of the 5 self-weaned patients. The prospectively weaned recipients (93 Liver s; 2 liver/ kidney) had undergone transplantation under immunosuppress ion based on azathioprine (AZA, through 1979), cyclosporine (CsA, 1980 -1989), or tacrolimus (TAG, 1989-1994). In patients on CsA or TAC base d cocktails, the adjunct drugs were weaned first in the early part of the trial. Since 1994, the T cell-directed drugs were weaned first. Th ree of the 5 original self-weaned recipients remain well after drug-fr ee intervals of 14 to 17 years. A fourth patient died in a vehicular a ccident after 11 years off immunosuppression, and the fifth patient un derwent retransplantation because of hepatitis C infection after 9 dru g free years; their allografts had no histopathologic evidence of reje ction. Eighteen (19%) of the 95 patients in the prospective series hav e been drug free for from 10 months to 4.8 years. In the total group, 18 (19%) have had biopsy proved acute rejection; 7 (7%) had a presumed acute rejection without biopsy; 37 (39%) are still weaning; and 12 (1 3%, all well) were withdrawn from the protocol at reduced immunosuppre ssion because of noncompliance (n=8), recurrent PBC (n=2), pregnancy ( n=1), and renal failure necessitating kidney transplantation (n=1), No patients were formally diagnosed with chronic: rejection, but 3 (3%) were placed back on preexisting immunosuppression or switched from cyc losporine (CsA) to tacrolimus (TAG) because of histopathologic evidenc e of duct injury. Two patients with normal liver function died during the trial, both from complications of prior chronic immunosuppression. No grafts suffered permanent functional impairment and only one patie nt developed temporary jaundice, Long surviving liver transplant recip ients are systematically overimmunosuppressed. Consequently, drug wean ing, whether incomplete or complete, is an important management strate gy providing it is done slowly under careful physician surveillance, C omplete weaning from CsA-based regimens has been difficult. Disease re currence during drug withdrawal was documented in 2 of 13 patients wit h PBC and could be a risk with other autoimmune disorders.