The Influence of Preservation Injury on Rejection in the Hepatic Transplant Recipient

HEPAT 01243FK 506 pre-treatment is associated with reduced levels of tumor necrosis factor and interleukin 6 following hepatic ischemiajreperfusion Using a rat model, the effect of pre-treatment with FK 506 on hepatic ischemia/reperfusion injury was investigated. All control animals died within 72 h of the ischemia/reperfusion injury. Pre-treatment of the animals with FK 506 (OJ mg/kg in 0.5 ml saline) administered intravenously improved survival. The most striking protection against fatal ischemia/reperfusion injury was achieved in rats that were given FK 506 6 and 24 h prior to the induction of the hepatic ischemic insult (70% and 80% 10-day survival rates, respectively). The hepatoprotective effect of FK 506 was assessed further in a second experiment in which the serum levels of tumor necrosis factor (TNF) and interleukin 6 (IL-6) were measured. These results suggest that a 60-min period of hepatic ischemia and subsequent reperfusion triggers the release of both TNF and IL-6, and that FK 506 pre-treatment (6 h before the ischemic episode) significantly inhibits the production and/or release of these two cytokines compared to untreated controls. These data provide additional information concerning the immunosuppressive and hepatoprotective activities of FK 506. Based upon these data, it is probable that FK 506 attenuates hepatic ischemiajreperfusion injury, at least in part, by reducing TNF and IL-6 levels.

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“…In turn. the immune response becomes more intense (35). Since both CsA and FK 506 are immunosuppressive as well as hepatotrophic.…”

Section: Discussionmentioning

confidence: 99%

FK 506 pre-treatment is associated with reduced levels of tumor necrosis factor and interleukin 6 following hepatic ischemia/reperfusion

Sakr

McClain

Gavaler

et al. 1993

Journal of Hepatology

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“…3 Experience graft. 16,19,20 The clinical significance of this antigen shedding is unknown; authors in a recent report were in kidney transplantation has shown a clear survival advantage when patients receive a graft from a living unable to correlate frequency of rejection with cold ischemia time or evidence of preservation injury on liver related donor. 8,14 The incidence of rejection may be reduced by as much as 15% over the first year, and the biopsy.…”

Section: Episodesmentioning

confidence: 99%

Allograft rejection in pediatric recipients of living related liver transplants

et al. 1996

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The purpose of this study was to compare the inci-dence and severity of rejection episodes in a group of dence and severity of rejection episodes in a group of children receiving living related orthotopic liver transchildren receiving living related orthotopic liver trans-plants (LRLT) versus patients receiving cadaveric liver plants (LRLT) versus children receiving cadaveric liver transplants (CLT). transplants (CLT). Thirty-eight patients received pri-PATIENTS AND METHODS mary LRLT and 54 patients received CLT during a 3-year period ending June 1993. Baseline immunosuppressionThe study population included all pediatric patients underconsisted of cyclosporin, azathioprine, and corticoste-going primary orthotopic liver transplantation at the Univerroids. Rejection episodes were confirmed by liver histol-sity of Chicago during a 3-year period beginning June 1990. ogy and were treated initially with pulse intravenous Patients were divided into two groups: those receiving their methylprednisolone, 10 mg/kg/d for 3 days. Steroid-resis-first liver transplant from a cadaveric donor (CLT), and those tant rejection was treated with OKT3 or FK506. The me-receiving their first graft from a living related donor (LRLT). dian patient ages were 1.3 years for the CLT and .8 years Patients who died or required a second transplantation durfor the LRLT recipients. Acute cellular rejection devel-ing the first 7 postoperative days were excluded from the oped in 78% of the CLT grafts and 74% of the LRLT grafts study groups. Patients were also excluded if they were partic-(P Å ns). However, steroid-resistant rejection was signifi-ipating in an experimental protocol studying primary immucantly less frequent in the LRLT recipients, 13% versus nosuppression with FK506, although evaluation of data with 43% in the CLT recipients (P õ .01). Ductopenic rejection the inclusion of this cohort of patients yielded similar results. was diagnosed in 20% of CLT and 8% of LRLT grafts (P All patients had regular evaluation from the time of trans-õ .10), and graft loss caused by rejection was 9% in the plantation, which resulted in a follow-up period of 12 to 48 CLT and 3% in the LRLT group (P Å ns). In conclusion, months. Evaluation for clinical or biochemical evidence of the overall incidence of rejection is the same in LRLT rejection was performed at least monthly for the first 6 and CLT recipients, but LRLT recipients are less likely months after transplantation and then at least every 3 than CLT recipients to develop steroid-resistant rejec-months for 1 year. Patients who were 18 months posttranstion or ductopenic rejection. (HEPATOLOGY 1996;23:40-plantation were evaluated at 6-month intervals if there had 43.) been no rejection in the preceding observation period. Data were collected by retrospective chart review and included episodes of rejection, immunosuppressive therapy, Orthotopic liver transplantation using a segment of graft loss caused by rejection, and overall survival. Average liver from a living adult donor has become an accepted who...

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“…Reduced Kupffer cell function of the engrafted liver due to ischemic preservation damage and early graft rejection reduce bile production. This enhances the likelihood of various intestinal bacteria invading the bile tree [3,13]. Furthermore, thrombosis of the hepatic artery with possible ischemic damage of the bile duct epithelium, and bile duct anastomosis without an intact sphincter of Oddi in choledochojejunostomy, have previously been found in our patients and by others to be risk factors for infections and bacteremia due to the intestinal flora [2, 25, 371.…”

Section: Discussionmentioning

confidence: 73%

Stool cultures obtained before liver transplantation are useful for choice of perioperative antibiotic prophylaxis

Barkholt

Andersson

Ericzon

et al. 1997

Transplant International

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Stool cultures obtained before liver transplantation are useful for choice of perioperative anti biotic prophylaxisAbstract Bacterial infections, especially cholangitis, are still common complications after liver transplantation (LTx). During recent years, multiresistant enterococci have become a nosocomial problem in transplant units. The present prospective study on 26 patients, including 24 patients with chronic liver disease, demonstrated that enterococci were the predominant micro-organism involved in post-LTx bacterial infections. They were cultured in the feces and in other sites of 10 out of 13 (77 %) patients who underwent extensive examinations. Ampicillin-resistant Enterococcus faecium strains were isolated in urine or feces of 2 of the 13 patients prior to LTx. Similarly, resistance to ampicillin and gentamicin, the empirically used antibiotics for patients with fever of unknown origin, was found in E. faecium strains in 3 and 2 patients, respectively. Moreover, multiresistant E. faecium and E. faecalis strains were demonstrated in 46 % of the patients in the postoperative period (3 months). However, no vancomycin-resistant enterococci were isolated. The use of antibiotics within 4 months prior to LTx significantly increased the risk of developing ampicillin-resistant bacteria at the time of LTx and of infections with bacteria of enteric origin after LTx ( P = 0.03 and 0.01, respectively). We conclude that stool and urine cultures performed prior to LTX may be useful for selecting prophylactic antibiotic regimens.

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The Influence of Preservation Injury on Rejection in the Hepatic Transplant Recipient

Cited by 264 publications

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FK 506 pre-treatment is associated with reduced levels of tumor necrosis factor and interleukin 6 following hepatic ischemia/reperfusion

FK 506 pre-treatment is associated with reduced levels of tumor necrosis factor and interleukin 6 following hepatic ischemia/reperfusion

Allograft rejection in pediatric recipients of living related liver transplants

Stool cultures obtained before liver transplantation are useful for choice of perioperative antibiotic prophylaxis

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