Conversion of Liver Allograft Recipients From Cyclosporine to Fk506 Immunosuppressive Therapy—a Clinicopathologic Study of 96 Patients

Demetris, Anthony J.; Fung, John J.; Todo, Satoru; McCauley, Jerry; Jain, A.; Takaya, Shunichi; Alessiani, M.; Abu‐Elmagd, Kareem; Thiel, David H. Van; Starzl, Thomas E.

doi:10.1097/00007890-199205000-00017

Cited by 119 publications

(61 citation statements)

References 8 publications

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“…Normalization of liver function parameters was slow in these patients after conversion to tacrolimus, with most parameters normalizing after 6 months. This has been previously described by other investigators 5,6,9 and may be related to a period of liver regeneration after damage from rejection episodes. This normalization process was similar in the Rej and Int patients in the current study.…”

Section: Discussionsupporting

confidence: 71%

“…In addition, tacrolimus has been used as a rescue primary immunosuppressant in patients with refractory rejection or intolerance of cyclosporine (CyA), with the majority of such use in liver transplant recipients. 5,6 In this study, patients who were converted to tacrolimus because of refractory rejection were compared with those converted because of intolerance.…”

mentioning

confidence: 99%

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Tacrolimus rescue in liver transplant patients with refractory rejection or intolerance or malabsorption of cyclosporine

Klein

1999

Liver Transpl

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Tacrolimus is an effective immunosuppressant in the rescue of liver allograft patients in whom conventional immunosuppression failed. Efficacy and safety were examined in a multicenter trial of liver transplant recipients converted to tacrolimus because of rejection despite cyclosporine (CyA) therapy or intolerance to CyA. Six hundred seventy-seven patients were enrolled onto the study; 475 patients for rejection, 197 patients for intolerance, and 5 patients treated compassionately. The mean daily dose of tacrolimus was less in the intolerance (Int) patients throughout the study: 0.22 versus 0.17 mg/kg at 1 week and 0.14 versus 0.11 mg/kg at 24 months in rejection (Rej) and Int patients, respectively. Mean blood levels paralleled dosing in both groups, but were greater in the Rej patients (10.7 v 8.3 ng/mL at 18 months). Kaplan-Meier estimates of patient and graft survival were similar in the two groups. Patient survival rates were 80.1% and 81.5%, and graft survival rates were 72.7% and 73.9% at 24 months in the Rej and Int patients, respectively. Most adverse events occurred with a similar incidence in the two groups. Those with a 4% or greater incidence were fever, viral hepatitis, and pneumonia. The incidence of sepsis, gastrointestinal hemorrhage, kidney failure, and convulsion was greater in the Int group. The incidence of abnormal liver function test results, hyperglycemia, headache, and abnormal kidney function was greater in the Rej group. Mean liver function test results decreased with time postrescue in both groups. Mean serum creatinine level increased from baseline to 18 months postrescue in both groups (1.44 to 1.51 mg/dL for Int patients, 1.14 to 1.48 mg/dL for Rej patients). We conclude tacrolimus is safe and effective rescue in liver transplant recipients with rejection or CyA intolerance.

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Section: Discussionsupporting

confidence: 71%

mentioning

confidence: 99%

Tacrolimus rescue in liver transplant patients with refractory rejection or intolerance or malabsorption of cyclosporine

Klein

1999

Liver Transpl

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“…Fewer blastic lymphocytes, slightly greater interface activity, less venous subendothelial inflammation, and slightly more lobular activity cause biopsies with LAR to resemble chronic hepatitis. 4,57 LAR can also present as isolated perivenular inflammation and hepatocyte dropout (so-called "central perivenulitis") [58][59][60] and evolve into typical chronic rejection with ductopenia. 61 Subendothelial inflammation of portal or central veins is not a required finding in such cases.…”

Section: Generalized Criteriamentioning

confidence: 99%

Liver biopsy interpretation for causes of late liver allograft dysfunction

2006

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Evaluation of needle biopsies and extensive clinicopathological correlation play an important role in the determination of liver allograft dysfunction occurring more than 1 year after transplantation. Interpretation of these biopsies can be quite difficult because of the high incidence of recurrent diseases that show histopathological, clinical, and serological features that overlap with each other and with rejection. Also, more than one insult can contribute to allograft injury. In an attempt to enable centers to compare and pool results, improve therapy, and better understand pathophysiological disease mechanisms, the Banff Working Group on Liver Allograft Pathology herein proposes a set of consensus criteria for the most common and problematic causes of late liver allograft dysfunction, including late-onset acute and chronic rejection, recurrent and new-onset viral and autoimmune hepatitis, biliary strictures, and recurrent primary biliary cirrhosis and primary sclerosing cholangitis. A discussion of differential diagnosis is also presented. (HEPATOLOGY 2006;44:489-501.)

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“…These data pertain to the use of tacrolimus as a primary immunosuppressant after renal transplantation. In patients receiving intravenous tacrolimus as "rescue" therapy for refractory renal or hepatic allograft rejection, initial nephrotoxicity is seen in nearly all patients (8,(49)(50)(51).…”

Section: Clinical Features Of Tacrolimus Nephrotoxicitymentioning

confidence: 99%