Successful withdrawal of prednisone after adult liver transplantation for autoimmune hepatitis

Trouillot, T; Shrestha, Roshan; Kam, Igal; Wachs, Michael; Everson, Gregory T.

doi:10.1002/lt.500050514

Cited by 62 publications

(55 citation statements)

References 23 publications

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“…15 It was shown that 25% of patients progress to chronic hepatitis and cirrhosis within 5 years of transplantation. 16 A recent study from the United Network for Organ Sharing liver transplant database reported that the rate and severity of HCV recurrence, as well as patient and graft survival rates, were similar in patients administered CsA or tacrolimus maintenance therapy. Because of concerns related to steroid promotion of viral replication, discontinuation of steroid therapy in patients undergoing transplantation for HBV and HCV is recommended.…”

Section: Specific Patient Issues Viral Hepatitismentioning

confidence: 99%

Long-term immunosuppression and drug interactions

Levy

2001

Liver Transplantation

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Section: Specific Patient Issues Viral Hepatitismentioning

confidence: 99%

Long-term immunosuppression and drug interactions

Levy

2001

Liver Transplantation

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“…However, several trials have shown success in withdrawing steroid therapy at short time intervals after OLT. [14][15][16] Previous attempts at complete steroid abstinence in OLT have had mixed results, with a significant number of patients subsequently requiring steroid treatment for rejection. [5][6][7][8] Tisone et al 6 randomized 45 patients to the administration of cyclosporine and azathioprine with or without steroids.…”

Section: Discussionmentioning

confidence: 99%

Steroid-free liver transplantation using rabbit antithymocyte globulin induction: Results of a prospective randomized trial

Eason

Loss

Blazek

et al. 2001

Liver Transplantation

121

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Steroids have been 1 of the primary modes of immunosuppression since the inception of transplantation and have been credited with both the prevention and treatment of rejection. Steroids also have been held responsible for increased infections, posttransplantation diabetes, and recurrent hepatitis after orthotopic liver transplantation (OLT). The purpose of this ongoing prospective randomized trial is to eliminate steroid use in OLT through induction with rabbit antithymocyte globulin (RATG). This is the first report of a prospective randomized trial in OLT achieving complete absence of steroids. Seventy-one adult patients were prospectively randomized to administration of RATG or steroids. Thirty-six patients were randomized to the administration of RATG induction at a dose of 1.5 mg/kg intravenously (IV) beginning during the anhepatic phase. No steroids were administered. Patients were administered a second 1.5-mg/kg dose of RATG post-OLT day 1. Thirty-five patients were randomized to the administration of methylprednisolone, which had been our standard immunosuppressive protocol. These patients were administered methylprednisolone, 1,000 mg IV, initiated during the anhepatic phase and followed by steroid taper. Maintenance immunosuppression consisted of tacrolimus and mycophenolate, with or without prednisone. Three patients died in each group, for an overall survival rate of 91% in each group. One patient in each group required re-OLT, for a graft survival rate of 89% in each group. Seven patients administered RATG had biopsy-proven rejection (20.5%), all of whom were successfully treated by increasing tacrolimus doses. Eleven patients administered steroid had biopsy-proven rejection (32%), 7 (64%) of whom required additional steroids for treatment, whereas 4 patients (36%) were successfully treated by increasing tacrolimus doses. The incidence of rejection was not statistically significant; however, there was a significant difference in the incidence of steroid-requiring rejection (P ‫؍‬ .01). The incidence of recurrent hepatitis C was 50% in RATG patients and 71% in steroid patients (P ‫؍‬ not significant). The incidence and severity of infectious complications were slightly lower in RATG patients, accounted for by a greater incidence of cytomegalovirus (CMV) infection in the steroid patients. RATG induction enables complete avoidance of steroid use in OLT with a trend toward a lower rejection rate, decreased incidence of post-OLT diabetes and recurrent hepatitis C, and decreased CMV infection. This prospective randomized trial gives encouraging support that steroids can be safely eliminated in OLT. (Liver Transpl 2001;7: 693-697.) S teroids have been a cornerstone of immunosuppression since the inception of transplantation and are credited with both the prevention and treatment of rejection. However, steroids have also been shown to increase infectious complications, bone disease, and posttransplantation diabetes and possibly increase the incidence and severity of recurrent hepatitis C virus (HCV) infecti...

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“…Knowledge in each of these areas is particularly important because ideal immunosuppressive regimens after transplantation are being defined that emphasize early reduction in corticosteroid therapy and its ultimate withdrawal. 15,18 This report assesses the frequency, risk factors, and consequences of recurrent autoimmune hepatitis after liver transplantation in patients who have been systematically followed, evaluated by liver biopsy examinations at predefined intervals, and managed with similar immunosuppressive regimens. Diagnostic criteria, based on those codified by an international panel, are applied to all cases to ensure consistent and accurate diagnoses.…”

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confidence: 99%

“…8 However, findings in various centers have been discrepant regarding the prevalence of recurrence, its consequences, and its risk factors. The importance of HLA-DR3 mismatching between donor and recipient 3,5,6,11,12,13 and the impact of corticosteroid withdrawal on the recurrence of autoimmune hepatitis 5,9,14,18 are now disputed. Optimal results after transplantation require clarification of factors contributing to recurrence and better understanding of the frequency and consequences of recurrent disease.…”

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confidence: 99%

Recurrent autoimmune hepatitis after orthotopic liver transplantation

González-Koch¹,

Czaja²,

Carpenter³

et al. 2001

Liver Transpl

182

156

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To determine the frequency, risk factors, and consequences of recurrent autoimmune hepatitis after liver transplantation, 41 patients with type 1 disease were monitored after surgery in accordance with a surveillance protocol. Tacrolimus or cyclosporine plus prednisone were administered to each patient, and liver biopsy examinations were performed at least annually according to protocol. Corticosteroid therapy was ultimately discontinued in only 2 patients. Recurrent disease was defined as the presence of lymphoplasmacytic infiltrates in liver tissue in the absence of other causes of allograft dysfunction. Autoimmune hepatitis recurred in 7 patients (17%), and the mean time to recurrence was 4.6 ؎ 1 years. Recurrence was asymptomatic in 4 of 7 patients and detected only by surveillance liver biopsy assessment in 2 patients. Histological changes were mild, and there was no progression to cirrhosis during 4.9 ؎ 0.9 years of observation. Five-year patient (86% v 82%; P ‫؍‬ .9) and graft (86% v 67%; P ‫؍‬ .5) survival rates were not statistically different between patients with and without recurrent disease. HLA-DR3 or HLA-DR4 occurred more commonly in patients with than without recurrence (100% v 40%; P ‫؍‬ .008) and healthy subjects (100% v 49%; P ‫؍‬ .01). Recurrent disease was unrelated to donor HLA status. In conclusion, recurrence after transplantation for type 1 autoimmune hepatitis is common. Its mild manifestations and favorable prognosis may reflect early detection by a surveillance protocol and/or continuous corticosteroid treatment. L iver transplantation is effective in the treatment of decompensated autoimmune hepatitis. Five-year patient and graft survival rates range from 83% to 92%, 1,2 and the actuarial 10-year survival rate after transplantation is 75%. 3,4 Furthermore, autoantibodies and hypergammaglobulinemia disappear in most patients within 2 years. 1,2 Despite these successes, recurrent disease is possible, 2,3,5-13 and recent reports have indicated that it may lead to cirrhosis and graft failure. 2,8,12 Furthermore, the immunoreactive propensity of the recipient may contribute to greater frequencies of acute rejection, steroid-resistant rejection, and chronic rejection, especially if corticosteroids are withdrawn in the posttransplantation period. [12][13][14][15] The reasons for recurrent disease are unclear, but associations have been made with corticosteroid withdrawal, 5,9,11,16 implantation of an HLA-DR3-negative liver into a HLA-DR3-positive recipient, 5,6,17 immunosuppressive regimens based on tacrolimus, 8,10,12 and pediatric propensities for aggressive disease. 8 However, findings in various centers have been discrepant regarding the prevalence of recurrence, its consequences, and its risk factors. The importance of HLA-DR3 mismatching between donor and recipient 3,5,6,11,12,13 and the impact of corticosteroid withdrawal on the recurrence of autoimmune hepatitis 5,9,14,18 are now disputed. Optimal results after transplantation require clarification of factors contributing to recurre...

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Successful withdrawal of prednisone after adult liver transplantation for autoimmune hepatitis

Cited by 62 publications

References 23 publications

Long-term immunosuppression and drug interactions

Long-term immunosuppression and drug interactions

Steroid-free liver transplantation using rabbit antithymocyte globulin induction: Results of a prospective randomized trial

Recurrent autoimmune hepatitis after orthotopic liver transplantation

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