Promising early results with immunosuppression using rabbit anti-thymocyte globulin and steroids with delayed introduction of tacrolimus in adult liver transplant recipients

Tector, A. Joseph; Fridell, Jonathan A.; Mangus, Richard S.; Shah, Apeksha; Milgrom, Martin L.; Kwo, Paul Y.; Chalasani, Naga; Yoo, Hae Young; Rouch, Dale; Liangpunsakul, Suthat; Herring, Scott; Lumeng, Lawrence

doi:10.1002/lt.20085

Cited by 56 publications

(38 citation statements)

References 13 publications

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“…Importantly, anti-thymocyte globulin was not associated with an increased incidence of hepatitis C recurrence. 21,24 This low incidence of adverse events, especially infection, may be related to the relatively low mean cumulative dose of anti-thymocyte globulin (2.2 mg/kg) used to delay the initiation of CNI in contrast to the conventional 1.5 mg/kg/day for 3 to 7 days used in kidney transplantation as induction therapy. [25][26][27][28] Additionally, the control patients required additional immunosuppression to treat acute rejection, which might lead to increased overall immunosuppression load and an increased incidence of infection.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14][15] Delaying the initiation of the nephrotoxic CNIs cyclosporine and tacrolimus until renal function recovers appears to be a logical approach to minimize early renal dysfunction in liver transplantation. Results from recent clinical studies have demonstrated the safety and efficacy of this strategy; [16][17][18][19][20][21] however, there is concern that delaying the initiation of CNI may place patients at risk for early acute rejection.…”

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confidence: 99%

“…allows for delayed initiation of CNI without an increased risk of acute rejection in kidney transplant recipients, 22,23 and because it has been used safely in liver transplant recipients, 18,[21][22][23][24] we postulate that delaying the initiation of CNI with anti-thymocyte globulin may be safe and effective in preserving renal function in liver transplant recipients with renal dysfunction. We therefore conducted a retrospective study comparing the outcomes of liver transplant recipients with renal dysfunction who received either anti-thymocyte globulin and delayed initiation of CNI (anti-thymocyte globulin group) or no antibody and early initiation of CNI (control group).…”

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confidence: 99%

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Preserving renal function in liver transplant recipients with rabbit anti-thymocyte globulin and delayed initiation of calcineurin inhibitors

et al. 2007

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Early renal dysfunction following liver transplantation is associated with increased morbidity and mortality. To evaluate the impact of delayed initiation of calcineurin inhibitor on renal function, we conducted a retrospective study comparing 118 liver transplant recipients who received rabbit anti-thymocyte globulin and delayed initiation of calcineurin inhibitor with 80 liver transplant recipients who received no antibody and early initiation of calcineurin inhibitor (control group). All patients received mycophenolate mofetil and steroids. Delayed calcineurin inhibitor initiation with anti-thymocyte globulin was associated with significant improvement in renal function throughout the first year post-transplant. At 12 months post-transplant, patients treated with this regimen experienced lower serum creatinine (1.4 Ϯ 0.5 versus 1.7 Ϯ 0.5 mg/dL, P Ͻ 0.001), a higher estimated glomerular filtration rate (57.4 Ϯ 20.5 versus 43.7 Ϯ 14.4 mL/min/1.73 m 2 , P Ͻ 0.001), and less dependence on dialysis (0.8% versus 13%, P Ͻ 0.001) in comparison with no antibody and early calcineurin inhibitor initiation. Patient survival and graft survival were similar between groups; however, there was a trend of a lower incidence of early biopsy-proven acute rejection with anti-thymocyte globulin. Overall infection and cytomegalovirus infection were significantly lower in anti-thymocyte globulin-treated patients, and there was no increased incidence of hepatitis C recurrence in comparison with controls. In conclusion, delayed initiation of calcineurin inhibitor with anti-thymocyte globulin in liver transplant recipients is safe and is associated with improvements in renal function and a lower incidence of early acute rejection in comparison with no antibody and early initiation of calcineurin inhibitor. Liver Transpl 14: 66-72, 2008.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Preserving renal function in liver transplant recipients with rabbit anti-thymocyte globulin and delayed initiation of calcineurin inhibitors

et al. 2007

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“…No study has yet assessed the clinical effects of rATG versus IL-2R antibodies as induction therapies in liver transplant, although 1 study reported good overall patient survival (96% at 17 mo) using rATG. 9 We hypothesized that the alternative use of rATG versus IL-2R antibody would be associated with a decreased rate of ACR and improved patient and graft survival rates. We designed this study to compare clinical outcomes of these 2 induction protocols in liver transplant recipients.…”

Section: Introductionmentioning

confidence: 99%

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Montenovo

Jalikis²,

Li³

et al. 2017

Exp Clin Transplant

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Objectives: The use of induction therapy in liver transplant is debatable. We aimed to compare clinical outcomes of different induction protocols in liver transplant recipients. Materials and Methods: This was a retrospective cohort analyses using the University of Washington Transplant Database from January 2005 to May 2012 for adult (≥ 18 y old) primary liver transplant patients. All patients received induction therapy. Maintenance immuno suppressive agents were tacrolimus or tacrolimus-mycophenolate mofetil. Primary endpoints were acute cellular rejection, patient survival, and graft survival. In patients with chronic hepatitis C, the degree of histologic inflammation or fibrosis at 1 year was assessed. Cox proportional hazards models were constructed to evaluate variables associated with both patient and graft survival. Results: We identified 595 patients: 322 patients received rabbit antithymocyte globulin and 273 received interleukin 2 receptor blocker. Acute cellular rejection was higher in patients who received interleukin 2 receptor blocker than in patients who received rabbit antithymocyte globulin (27% vs 18%; P < .03). Both patient survival at 1 year (95% vs 90%), 3 years (92% vs 87%), and 5 years (86% vs 80%) and graft survival at 1 year (93% vs 88%), 3 years (90% vs 86%), and 5 years (83% vs 78%) were superior with rabbit antithymocyte globulin than with the interleukin 2 receptor blocker (P < .002). In patients with hepatitis C virus, type of induction therapy did not have any effect on the timing of hepatitis C virus recurrence. At 1 year after transplant, 33.3% in the rabbit antithymocyte globulin group had grade 3/4 inflammation and 10.2% had stage 3/4 fibrosis, compared with 16.8% and 4.8% in the interleukin 2 receptor blocker group (P ≤ .002 and not significant). Female recipient, Model for End-Stage Liver Disease score, hepatocellular carcinoma, and high preoperative serum creatinine levels were associated with less favorable patient and graft survival. Conclusions: Rabbit antithymocyte globulin is associated with lower rejection rate and improved patient and graft survival in liver transplant. Type of therapy affects the degree of histologic hepatitis C virus recurrence.

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“…Due to a lack of the United States Food and Drug was primarily used to delay introduction of CNIs in patients with preexisting renal dysfunction. 7,10 Early renal dysfunction has been linked to chronic kidney failure, which increases morbidity and mortality in liver transplant patients. 11,12 Bajjoka and colleagues utilized daily RATG dosing in patients with preexisting kidney dysfunction to delay CNI introduction.…”

Section: Polyclonal Antibodiesmentioning

confidence: 99%