Does tacrolimus offer virtual freedom from chronic rejection after primary liver transplantation? Risk and prognostic factors in 1,048 liver transplantations with a mean follow-up of 6 years

Tacrolimus has proven to be a potent immunosuppressive agent in liver transplantation (LT). Its introduction has led to significantly less frequent and severe acute rejection. Little is known about the rate of chronic rejection (CR) in primary LT using tacrolimus therapy. The aim of the present stud...

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Published in:Liver transplantation 2001-07, Vol.7 (7), p.623-630
Main Authors: Jain, Ashok, Demetris, Anthony Jake, Kashyap, Randeep, Blakomer, Karen, Ruppert, Kris, Khan, Akhtar, Rohal, Susan, Starzl, Thomas E., Fung, John J.
Format: Article
Language:English
Subjects:
Adult
Age
Bilirubin
Biopsy
Cholangitis
Cirrhosis
Donors
Follow-Up Studies
Graft rejection
Graft Rejection - immunology
Graft Rejection - prevention & control
Hepatitis B virus
Hepatitis C virus
Humans
Immunosuppressive agents
Immunosuppressive Agents - therapeutic use
Liver
Liver transplantation
Liver Transplantation - immunology
primary biliary cirrhosis
Prognosis
Risk Factors
Statistical analysis
Steroid hormones
Survival
Tacrolimus
Tacrolimus - therapeutic use
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Summary:Tacrolimus has proven to be a potent immunosuppressive agent in liver transplantation (LT). Its introduction has led to significantly less frequent and severe acute rejection. Little is known about the rate of chronic rejection (CR) in primary LT using tacrolimus therapy. The aim of the present study is to examine the long-term incidence of CR, risk factors, prognostic factors, and outcome after CR. The present study evaluated the development of CR in 1,048 consecutive adult primary liver allograft recipients initiated and mostly maintained on tacrolimus-based immunosuppressive therapy. They were evaluated with a mean follow-up of 77.3 ± 14.7 months (range, 50.7 to 100.1 months). To assess the impact of primary diagnosis on the rate and outcome of CR, the population was divided into 3 groups. Group I included patients with hepatitis C virus (HCV)- or hepatitis B virus (HBV)-induced cirrhosis (n = 312); group II included patients diagnosed with primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), or autoimmune hepatitis (AIH; n = 217); and group III included patients with all other diagnoses (n = 519). Overall, 32 of 1,048 patients (3.1%) developed CR. This represented 13 (4.1%), 12 (5.5%), and 7 patients (1.3%) in groups I, II, and III, respectively. The relative risk for developing CR was 3.2 times greater for group I and 4.3 times greater for group II compared with group III. This difference was statistically significant ( P = .004). The incidence of acute rejection and total number of acute rejection episodes were significantly greater in patients who developed CR compared with those who did not ( P < .0001). Similarly, the mean donor age for CR was significantly older than for patients without CR (43.0 v 36.2 years; P = .02). Thirteen of the 32 patients (40.6%) who developed CR retained their original grafts for a mean period of 54 ± 25 months after diagnosis. Seven patients (21.9%) underwent re-LT, and 12 patients (38.3%) died. Serum bilirubin levels and the presence of arteriopathy, arterial loss, and duct loss on liver biopsy at the time of diagnosis of CR were significantly greater among the 3 groups of patients. In addition, patient and graft survival for group I were significantly worse compared with groups II and III. We conclude that CR occurred rarely among patients maintained long term on tacrolimus-based immunosuppressive therapy. When steroid use is controlled, the incidence of acute rejection, mean donor age, HBV- and/or
ISSN:1527-6465
1527-6473
DOI:10.1053/jlts.2001.25364