Chronic Liver Allograft Rejection in a Population Treated Primarily With Tacrolimus as Baseline Immunosuppression

Blakolmer, Karin; Jain, Ashok Kumar; Ruppert, K.; Gray, Edward A.; Duquesnoy, René J.; Murase, Noriko; Starzl, TE; Fung, John J.; Demetris, Anthony J.

doi:10.1097/00007890-200006150-00019

Cited by 78 publications

(84 citation statements)

References 35 publications

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“…48,49 It is possible that older donors have preexisting arteriopathy in the allograft and the biliary epithelium is more susceptible to immunologic insult. 50 Several reports have found a relationship between HLA antigen matching and/or mismatching, positive lymphocytotoxic cross-matching, and the development of liver allograft CR. 30,31,[51][52][53][54][55] In this study, these factors did not predispose to the development of CR.…”

Section: Discussionmentioning

confidence: 99%

“…Detailed histopathologic findings in most of these patients have been previously reported. 18 Duct damage and duct atrophy were seen in the majority of patients who developed CR. The rate of duct loss was significantly greater for patients who required re-LT (P ϭ .011).…”

Section: Prognostic Factorsmentioning

confidence: 99%

“…[24][25][26] Details of histopathologic findings in most of these patients are presented elsewhere. 18 …”

Section: Pathological Evaluationmentioning

confidence: 99%

“…[8][9][10][11][12] Additional studies report that up to 70% of cases of CR occurring with CsA-based therapy may be halted or reversed after the initiation of tacrolimus therapy. [13][14][15][16][17] Although there are reports suggesting a reduction in the rate of CR among tacrolimus-treated patients compared with those maintained on CsA therapy, 8,18 relatively little is known about the rate of CR with long-term tacrolimus therapy. The aim of the present study is to examine the incidence and risk factors for the development of CR among patients on long-term tacrolimus therapy and study the clinical outcome with prognostic factors.…”

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confidence: 99%

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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

Jain

Demetris

Kashyap

et al. 2001

Liver Transplantation

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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 HCV-induced cirrhosis, or a diagnosis of PBC, PSC, or AIH were found to be predictors of CR. Greater values for serum bilirubin level, duct loss, arteriopathy, arteriolar loss, and presence of HCV or HBV were found to be poor prognostic factors for the 3 groups; greater total serum bilirubin value (P ‫؍‬ .05) was the only factor found to be significant between patients who had graft loss versus those who recovered. (Liver Transpl 2001;7:623-630.)

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Section: Discussionmentioning

confidence: 99%

Section: Prognostic Factorsmentioning

confidence: 99%

“…[24][25][26] Details of histopathologic findings in most of these patients are presented elsewhere. 18 …”

Section: Pathological Evaluationmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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

Jain

Demetris

Kashyap

et al. 2001

Liver Transplantation

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“…INTRODUCTION Hepatic transplantation is an accepted standard of care for end-stage liver disease. One-year survival rates approach 80% to 85% and late graft loss from chronic rejection is uncommon (1). Unfortunately, recurrence ofthe original disease is emerging as a major problem, affecting most viral hepatitis patients and 15% to 25% of those with autoimmune liver diseases within 5 years (2,3).…”

mentioning

confidence: 99%