IgG DONOR-SPECIFIC CROSSMATCHES ARE NOT ASSOCIATED WITH GRAFT REJECTION OR POOR GRAFT SURVIVAL AFTER LIVER TRANSPLANTATION

Donaldson, Peter; Thomson, Linda J.; Heads, A; UNDERBILL, JAMES A.; Vaughan, R. W.; Rolando, Nancy

doi:10.1097/00007890-199511150-00024

Cited by 39 publications

(21 citation statements)

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“…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. In summary, the incidence of CR is low among patients maintained long term on tacrolimus-based therapy.…”

Section: Discussionmentioning

confidence: 41%

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: 41%

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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“…However, recent reports do not support these observations. 7,8 This may be due to the differences of the sensitivity of the crossmatch test, and differences of the basic immunosuppression regimens. Antibodies to non-HLA target antigens may be important.…”

Section: Discussionmentioning

confidence: 99%

“…4,5 There have been many conflicting recent reports concerning a relationship between the bile duct-related complications or ductopenic chronic rejection and a positive crossmatch. [6][7][8] . We investigated the outcome of liver grafts from positive crossmatch donors, focusing on biliary complications and ductopenic chronic rejection, and we compared the results to a consecutive negative cross-match control group at the same time.…”

mentioning

confidence: 99%

Increased bile duct complications and/or chronic rejection in crossmatch positive human liver allografts

Takaya

Jain

Yagihashi

et al. 1999

Transplantation Proceedings

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Bile duct complications continue to be a significant cause of bile morbidity after orthotopic liver transplantation, with an incidence of 7% to 34% of patients. 1,2 Bile of duct obstruction, usually due to strictures, biliary leakage, and/or cholangitis, accounts for the majority of these complications. In contrast, although low incidence of chronic rejection has been reported under FK 506-based immunosuppression in early trials of liver transplantation, 3 chronic rejection after liver transplantation occurs in only 5% to 9% of cases, and it remains one of the most common causes of graft loss. 4,5 There have been many conflicting recent reports concerning a relationship between the bile duct-related complications or ductopenic chronic rejection and a positive crossmatch. [6][7][8] . We investigated the outcome of liver grafts from positive crossmatch donors, focusing on biliary complications and ductopenic chronic rejection, and we compared the results to a consecutive negative cross-match control group at the same time. CASE MATERIALSWe analyzed 306 consecutive adults (more than 16 years of age) primary liver transplant cases performed at Presbyterian University Hospital in Pittsburgh between November 13, 1989, and September 26, 1990. Twenty-eight (9.1%) patients were from a donor whose crossmatch test results were positive (more than 50% of donor lymphocytes were killed by dithiothreitolpretreated recipient serum). Selection of the contemporaneous 278 consecutive control patients whose crossmatch test results were negative when less than 10% of donor lymphocytes were killed, and were doubtfully or weakly positive when 11 % to 49% of donor lymphocytes were killed. None of the 306 patients received ABO blood group-incompatible grafts. All donor livers were preserved by University of Wisconsin solution.The study groups differed in crossmatch status, negative control (group 1, n = 278) and positive group (group 2, n = 28). There was a generally high degree of illness in both the positive crossmatch group and their controls, as defined by the United Network for Organ Sharing (UNOS) stratification (Table 1). The Crossmatch TestEach recipient's serum was drawn immediately before and after liver transplantation and tested for cytotoxic cross-matching activity before and after treatment with dithiothreitol (DTT), which inactivates IgM antibodies. 9 Donor T lymphocytes isolated from lymph nodes using CD3-conjugated dynabeads (Dynal, Great Neck. NY) were used.

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“…14 Liver transplants do not normally require MHC matching of donor and recipient, although the outcome is in some cases slightly better in patients who are MHC matched. 15 Unlike recipients of heart or kidney transplants, a proportion of liver transplant recipients with stable function can be removed totally from immunosuppression.…”

Section: The Phenomenon Of Spontaneous Liver Allograft Tolerancementioning

confidence: 99%

Immune activation is required for the induction of liver allograft tolerance: Implications for immunosuppressive therapy

Bishop

McCaughan

2001

Liver Transpl

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Liver transplants in many animal models are unusual because often they are not rejected even when transplanted across complete major histocompatibility complex barriers without immunosuppression. Their paradoxical behavior is even more obvious when the immune mechanism of acceptance is examined. Instead of acceptance resulting from a lack of immune response to the graft, the opposite occurs, and there is an unusual extensive increase in immune activation in acceptance compared with rejection. This abnormal extensive immune activation is driven by

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IgG DONOR-SPECIFIC CROSSMATCHES ARE NOT ASSOCIATED WITH GRAFT REJECTION OR POOR GRAFT SURVIVAL AFTER LIVER TRANSPLANTATION

Cited by 39 publications

References 0 publications

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

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

Increased bile duct complications and/or chronic rejection in crossmatch positive human liver allografts

Immune activation is required for the induction of liver allograft tolerance: Implications for immunosuppressive therapy

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