Reasons for long-term use of steroid in primary adult liver transplantation under tacrolimus.
BACKGROUND
Tacrolimus is a potent immunosuppressive agent that provides higher freedom from acute and chronic rejection than cyclosporine after liver transplantation (LTx). Initially, a steroid-free state was observed in about 70% of patients at 1 year; this did not change over the next 5 years. The present study identifies the various reasons why the remaining 30% of adult patients still require steroids even after 5 years after successful LTx.


METHODS
Eight hundred thirty-four consecutive patients who underwent LTx between August 1989 and December 1992 were included in this study. Four hundred ninety-nine patients were alive in January 1999 and were available for this study. The dose of steroid and the reason for steroid use were retrospectively determined from the clinical records.


RESULTS
Three hundred sixty-five patients (73.1%) were off steroid, whereas 134 patients (26.9%) were receiving prednisone (mean dose was 6.4+/-3.7 mg/day) at the time of the study. Four hundred and eight-four patients (97%) were off prednisone at some time after LTx; however, in 119 (23.8%) patients, steroids were reintroduced. Fifteen patients (3%) continued to receive prednisone; eight receive prednisone due to reluctance of the local physician to withdraw the medication; in five patients, the prednisone was not withdrawn because these patients were on cyclosporine; in the remaining two patients, repeated attempts to withdraw steroid resulted in a rise in liver function test. In the 49 (36.6%) of 119 patients in whom the steroid was reintroduced, it was restarted secondary to pathologically proven or clinically suspected rejection (group I). In five patients steroid was reintroduced for abnormal liver function after being off immunosuppression for treatment of a posttransplantation lymphoproliferative disorder. Six patients were noncompliant with their immunosuppressive medication, and the steroid was reintroduced to control rejection. Steroids were reintroduced in 30 patients (22.4%) for recurrence of original disease: primary biliary cirrhosis (n= 19), sclerosing cholangitis (n=6), and autoimmune hepatitis (n=5) (group II). In 24 patients (20.2%), steroids were reintroduced to lower the dose of tacrolimus secondary to nephrotoxicity. Six of these patients received kidney transplantation (group III). In 16 patients (13.4%) the steroid was reintroduced for concomitant medical problems, consisting of ulcerative/Crohn's colitis (n=6), adrenal insufficiency (n=5), hematological disorders (n=3), dermatitis (n=1), and rheumatoid arthritis (n=1) (group IV).


CONCLUSIONS
Ninety-seven percent of patients under tacrolimus were weaned off steroid; however, 23.8% required steroid reintroduction for late rejection, recurrence of autoimmune process(es), renal impairment, or the concomitant presence of other medical conditions. Although the use of other immunosuppressive agents may reduce the rate of reintroduction of steroid, long-term sustained freedom from steroid may not be possible in all patients under tacrolimus secondary to these conditions.
Jain
A
A
Department of Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, Pennsylvania, USA.
Kashyap
R
R
Marsh
W
W
Rohal
S
S
Khanna
A
A
Fung
J J
JJ
D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D013256:Steroids / Q000009:adverse effects / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors
D007166:Immunosuppressive Agents; D013256:Steroids; D011239:Prednisolone; D001379:Azathioprine; D016559:Tacrolimus