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5. Hepatocellular carcinoma progression during bridging before liver transplantation

Author

Renner, P, Da Silva, T, Schnitzbauer, A, Verloh, N, Schlitt, H, Geissler, E, Zulke, C, Lamby, P, Proneth, A, Duvoux, C, Burra, P, Jauch, K, Rentsch, M, Ganten, T, Schmidt, J, Settmacher, U, Heise, M, Rossi, G, Cillo, U, Kneteman, N, Adam, R, Van Hoek, B, Bachellier, P, Wolf, P, Rostaing, L, Bechstein, W, Rizell, M, Powell, J, Hidalgo, E, Gugenheim, J, Wolters, H, Brockmann, J, Roy, A, Mutzbauer, I, Schlitt, A, Beckebaum, S, Graeb, C, Nadalin, S, Valente, U, Sanchez Turrion, V, Jamieson, N, Scholz, T, Colledan, M, Fandrich, F, Becker, T, Soderdahl, G, Chazouilleres, O, Makisalo, H, Pageaux, G, Steininger, R, Soliman, T, De Jong, K, Pirenne, J, Margreiter, R, Pratschke, J, Pinna, A, Hauss, J, Schreiber, S, Strasser, S, Klempnauer, J, Troisi, R, Bhoori, S, Lerut, J, Bilbao, I, Klein, C, Konigsrainer, A, Otto, G, Mazzaferro, V, Neuhaus, P, Renner P., Da Silva T., Schnitzbauer A. A., Verloh N., Schlitt H. J., Geissler E. K., Zulke C., Lamby P. E., Proneth A., Duvoux C., Burra P., Jauch K. -W., Rentsch M., Ganten T. M., Schmidt J., Settmacher U., Heise M., Rossi G., Cillo U., Kneteman N., Adam R., Van Hoek B., Bachellier P., Wolf P., Rostaing L., Bechstein W. O., Rizell M., Powell J., Hidalgo E., Gugenheim J., Wolters H., Brockmann J., Roy A., Mutzbauer I., Schlitt A., Beckebaum S., Graeb C., Nadalin S., Valente U., Sanchez Turrion V., Jamieson N., Scholz T., Colledan M., Fandrich F., Becker T., Soderdahl G., Chazouilleres O., Makisalo H., Pageaux G. -P., Steininger R., Soliman T., De Jong K. P., Pirenne J., Margreiter R., Pratschke J., Pinna A. D., Hauss J., Schreiber S., Strasser S., Klempnauer J., Troisi R. I., Bhoori S., Lerut J., Bilbao I., Klein C. G., Konigsrainer A., Otto G., Mazzaferro V., Neuhaus P., Renner, P, Da Silva, T, Schnitzbauer, A, Verloh, N, Schlitt, H, Geissler, E, Zulke, C, Lamby, P, Proneth, A, Duvoux, C, Burra, P, Jauch, K, Rentsch, M, Ganten, T, Schmidt, J, Settmacher, U, Heise, M, Rossi, G, Cillo, U, Kneteman, N, Adam, R, Van Hoek, B, Bachellier, P, Wolf, P, Rostaing, L, Bechstein, W, Rizell, M, Powell, J, Hidalgo, E, Gugenheim, J, Wolters, H, Brockmann, J, Roy, A, Mutzbauer, I, Schlitt, A, Beckebaum, S, Graeb, C, Nadalin, S, Valente, U, Sanchez Turrion, V, Jamieson, N, Scholz, T, Colledan, M, Fandrich, F, Becker, T, Soderdahl, G, Chazouilleres, O, Makisalo, H, Pageaux, G, Steininger, R, Soliman, T, De Jong, K, Pirenne, J, Margreiter, R, Pratschke, J, Pinna, A, Hauss, J, Schreiber, S, Strasser, S, Klempnauer, J, Troisi, R, Bhoori, S, Lerut, J, Bilbao, I, Klein, C, Konigsrainer, A, Otto, G, Mazzaferro, V, Neuhaus, P, Renner P., Da Silva T., Schnitzbauer A. A., Verloh N., Schlitt H. J., Geissler E. K., Zulke C., Lamby P. E., Proneth A., Duvoux C., Burra P., Jauch K. -W., Rentsch M., Ganten T. M., Schmidt J., Settmacher U., Heise M., Rossi G., Cillo U., Kneteman N., Adam R., Van Hoek B., Bachellier P., Wolf P., Rostaing L., Bechstein W. O., Rizell M., Powell J., Hidalgo E., Gugenheim J., Wolters H., Brockmann J., Roy A., Mutzbauer I., Schlitt A., Beckebaum S., Graeb C., Nadalin S., Valente U., Sanchez Turrion V., Jamieson N., Scholz T., Colledan M., Fandrich F., Becker T., Soderdahl G., Chazouilleres O., Makisalo H., Pageaux G. -P., Steininger R., Soliman T., De Jong K. P., Pirenne J., Margreiter R., Pratschke J., Pinna A. D., Hauss J., Schreiber S., Strasser S., Klempnauer J., Troisi R. I., Bhoori S., Lerut J., Bilbao I., Klein C. G., Konigsrainer A., Otto G., Mazzaferro V., and Neuhaus P.

Abstract

Background: Recipient selection for liver transplantation in hepatocellular carcinoma (HCC) is based primarily on criteria affecting the chance of long-term success. Here, the relationship between pretransplant bridging therapy and long-term survival was investigated in a subgroup analysis of the SiLVER Study. Methods: Response to bridging, as defined by comparison of imaging at the time of listing and post-transplant pathology report, was categorized into controlled versus progressive disease (more than 20 per cent tumour growth or development of new lesions). Results: Of 525 patients with HCC who had liver transplantation, 350 recipients underwent pretransplant bridging therapy. Tumour progression despite bridging was an independent risk factor affecting overall survival (hazard ratio 1.80; P=0.005). For patients within the Milan criteria (MC) at listing, mean overall survival was longer for those with controlled versus progressive disease (6.8 versus 5.8 years; P<0.001). Importantly, patients with HCCs outside the MC that were downsized to within the MC before liver transplantation had poor outcomes compared with patients who never exceeded the MC (mean overall survival 6.2 versus 6.6 years respectively; P=0.030). Conclusion: Patients with HCCs within the MC that did not show tumour progression under locoregional therapy had the best outcomes after liver transplantation. Downstaging into the limits of the MC did not improve the probability of survival. Prognostic factors determining the long-term success of liver transplantation in patients with hepatocellular carcinoma are still under discussion. A subgroup analysis of the SiLVER trial showed that disease control under bridging therapy is strongly associated with improved prognosis in terms of overall survival. However, in tumours exceeding the limits of the Milan criteria, downstaging did not restore the probability of survival compared with that of patients within the Milan criteria.

Published
2021

6. mTOR Inhibition Is Most Beneficial After Liver Transplantation for Hepatocellular Carcinoma in Patients With Active Tumors

Author

Schnitzbauer, A, Filmann, N, Adam, R, Bachellier, P, Bechstein, W, Becker, T, Bhoori, S, Bilbao, I, Brockmann, J, Burra, P, Chazoullieres, O, Cillo, U, Colledan, M, Duvoux, C, Ganten, T, Gugenheim, J, Heise, M, van Hoek, B, Jamieson, N, de Jong, K, Klein, C, Klempnauer, J, Kneteman, N, Lerut, J, Makisalo, H, Mazzaferro, V, Mirza, D, Nadalin, S, Neuhaus, P, Pageaux, G, Pinna, A, Pirenne, J, Pratschke, J, Powel, J, Rentsch, M, Rizell, M, Rossi, G, Rostaing, L, Roy, A, Scholz, T, Settmacher, U, Soliman, T, Strasser, S, Soderdahl, G, Troisi, R, Turrion, V, Schlitt, H, Geissler, E, Schnitzbauer AA, Filmann N, Adam RP, Bachellier P, Bechstein WO, Becker T, Bhoori S, Bilbao I, Brockmann J, Burra P, Chazoullieres O, Cillo U, Colledan M, Duvoux C, Ganten TM, Gugenheim J, Heise M, van Hoek B, Jamieson N, de Jong KP, Klein CG, Klempnauer J, Kneteman N, Lerut J, Makisalo H, Mazzaferro V, Mirza DF, Nadalin S, Neuhaus P, Pageaux GP, Pinna AD, Pirenne J, Pratschke J, Powel J, Rentsch M, Rizell M, Rossi G, Rostaing L, Roy AP, Scholz T, Settmacher U, Soliman T, Strasser S, Soderdahl G, Troisi RI, Turrion VS, Schlitt HJ, Geissler EK, Schnitzbauer, A, Filmann, N, Adam, R, Bachellier, P, Bechstein, W, Becker, T, Bhoori, S, Bilbao, I, Brockmann, J, Burra, P, Chazoullieres, O, Cillo, U, Colledan, M, Duvoux, C, Ganten, T, Gugenheim, J, Heise, M, van Hoek, B, Jamieson, N, de Jong, K, Klein, C, Klempnauer, J, Kneteman, N, Lerut, J, Makisalo, H, Mazzaferro, V, Mirza, D, Nadalin, S, Neuhaus, P, Pageaux, G, Pinna, A, Pirenne, J, Pratschke, J, Powel, J, Rentsch, M, Rizell, M, Rossi, G, Rostaing, L, Roy, A, Scholz, T, Settmacher, U, Soliman, T, Strasser, S, Soderdahl, G, Troisi, R, Turrion, V, Schlitt, H, Geissler, E, Schnitzbauer AA, Filmann N, Adam RP, Bachellier P, Bechstein WO, Becker T, Bhoori S, Bilbao I, Brockmann J, Burra P, Chazoullieres O, Cillo U, Colledan M, Duvoux C, Ganten TM, Gugenheim J, Heise M, van Hoek B, Jamieson N, de Jong KP, Klein CG, Klempnauer J, Kneteman N, Lerut J, Makisalo H, Mazzaferro V, Mirza DF, Nadalin S, Neuhaus P, Pageaux GP, Pinna AD, Pirenne J, Pratschke J, Powel J, Rentsch M, Rizell M, Rossi G, Rostaing L, Roy AP, Scholz T, Settmacher U, Soliman T, Strasser S, Soderdahl G, Troisi RI, Turrion VS, Schlitt HJ, and Geissler EK

Abstract

Objective: The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial). Summary and Background Data: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial (Clinicaltrials.gov:NCT00355862), the effect of sirolimus on the recurrence of HCC after LTwas investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data. Patients and Methods: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models for overall survival (OS), DFS and a competing risk analysis for HCC recurrence. Results: Sirolimus use for >= 3 months after LT for HCC independently reduced the hazard for death in the multivariate analysis [hazard ratio (HR): 0.7 (95% confidence interval, CI: 0.52-0.96, P = 0.02). Most strikingly, patients with an alpha-fetoprotein (AFP) >= 10 ng/mL and having used sirolimus for >= 3 months, benefited most with regard to OS, DFS, and HCC-recurrence (HR: 0.49- 0.59, P = 0.0079- 0.0245). Conclusions: mTOR-inhibitor treatment with sirolimus for >= 3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients. Clinical Trial Registration: EudraCT: 2005-005362-36 Clinicaltrials.gov: NCT00355862.

Published
2020

7. HCC recurrence in HCV-infected patients after liver transplantation: SiLVER Study reveals benefits of sirolimus in combination with CNIs – a post-hoc analysis

Author

Werner, J, Hornung, M, Krah, R, Gotz, M, Schnitzbauer, A, Schlitt, H, Geissler, E, Zulke, C, Lamby, P, Proneth, A, Duvoux, C, Burra, P, Jauch, K, Rentsch, M, Ganten, T, Schmidt, J, Settmacher, U, Heise, M, Rossi, G, Cillo, U, Kneteman, N, Adam, R, Hoek, B, Bachellier, P, Wolf, P, Rostaing, L, Bechstein, W, Rizell, M, Powell, J, Hidalgo, E, Gugenheim, J, Wolters, H, Brockmann, J, Roy, A, Mutzbauer, I, Schlitt, A, Beckebaum, S, Graeb, C, Nadalin, S, Valente, U, Turrion, V, Jamieson, N, Scholz, T, Colledan, M, Fandrich, F, Becker, T, Soderdahl, G, Chazouilleres, O, Makisalo, H, Pageaux, G, Steininger, R, Soliman, T, Jong, K, Pirenne, J, Margreiter, R, Pratschke, J, Pinna, A, Hauss, J, Schreiber, S, Strasser, S, Klempnauer, J, Troisi, R, Bhoori, S, Lerut, J, Bilbao, I, Klein, C, Konigsrainer, A, Otto, G, Mazzaferro, V, Neuhaus, P, Werner J. M., Hornung M., Krah R., Gotz M., Schnitzbauer A. A., Schlitt H. J., Geissler E. K., Zulke C., Lamby P. E., Proneth A., Duvoux C., Burra P., Jauch K. -W., Rentsch M., Ganten T. M., Schmidt J., Settmacher U., Heise M., Rossi G., Cillo U., Kneteman N., Adam R., Hoek B., Bachellier P., Wolf P., Rostaing L., Bechstein W. O., Rizell M., Powell J., Hidalgo E., Gugenheim J., Wolters H., Brockmann J., Roy A., Mutzbauer I., Schlitt A., Beckebaum S., Graeb C., Nadalin S., Valente U., Turrion V. S., Jamieson N., Scholz T., Colledan M., Fandrich F., Becker T., Soderdahl G., Chazouilleres O., Makisalo H., Pageaux G. -P., Steininger R., Soliman T., Jong K. P., Pirenne J., Margreiter R., Pratschke J., Pinna A. D., Hauss J., Schreiber S., Strasser S., Klempnauer J., Troisi R. I., Bhoori S., Lerut J., Bilbao I., Klein C. G., Konigsrainer A., Otto G., Mazzaferro V., Neuhaus P., Werner, J, Hornung, M, Krah, R, Gotz, M, Schnitzbauer, A, Schlitt, H, Geissler, E, Zulke, C, Lamby, P, Proneth, A, Duvoux, C, Burra, P, Jauch, K, Rentsch, M, Ganten, T, Schmidt, J, Settmacher, U, Heise, M, Rossi, G, Cillo, U, Kneteman, N, Adam, R, Hoek, B, Bachellier, P, Wolf, P, Rostaing, L, Bechstein, W, Rizell, M, Powell, J, Hidalgo, E, Gugenheim, J, Wolters, H, Brockmann, J, Roy, A, Mutzbauer, I, Schlitt, A, Beckebaum, S, Graeb, C, Nadalin, S, Valente, U, Turrion, V, Jamieson, N, Scholz, T, Colledan, M, Fandrich, F, Becker, T, Soderdahl, G, Chazouilleres, O, Makisalo, H, Pageaux, G, Steininger, R, Soliman, T, Jong, K, Pirenne, J, Margreiter, R, Pratschke, J, Pinna, A, Hauss, J, Schreiber, S, Strasser, S, Klempnauer, J, Troisi, R, Bhoori, S, Lerut, J, Bilbao, I, Klein, C, Konigsrainer, A, Otto, G, Mazzaferro, V, Neuhaus, P, Werner J. M., Hornung M., Krah R., Gotz M., Schnitzbauer A. A., Schlitt H. J., Geissler E. K., Zulke C., Lamby P. E., Proneth A., Duvoux C., Burra P., Jauch K. -W., Rentsch M., Ganten T. M., Schmidt J., Settmacher U., Heise M., Rossi G., Cillo U., Kneteman N., Adam R., Hoek B., Bachellier P., Wolf P., Rostaing L., Bechstein W. O., Rizell M., Powell J., Hidalgo E., Gugenheim J., Wolters H., Brockmann J., Roy A., Mutzbauer I., Schlitt A., Beckebaum S., Graeb C., Nadalin S., Valente U., Turrion V. S., Jamieson N., Scholz T., Colledan M., Fandrich F., Becker T., Soderdahl G., Chazouilleres O., Makisalo H., Pageaux G. -P., Steininger R., Soliman T., Jong K. P., Pirenne J., Margreiter R., Pratschke J., Pinna A. D., Hauss J., Schreiber S., Strasser S., Klempnauer J., Troisi R. I., Bhoori S., Lerut J., Bilbao I., Klein C. G., Konigsrainer A., Otto G., Mazzaferro V., and Neuhaus P.

Abstract

Factors affecting outcomes in liver transplant (LTx) recipients with hepatocellular carcinoma (HCC) and hepatitis C viral (HCV) infection include the choice of immunosuppression. Here, we analyzed the HCV+ subgroup of patients from the randomized controlled, international SiLVER Study. We performed a post hoc analysis of 166 HCV+ SiLVER Study patients regarding HCC outcome after LTx. Control patients (group A: n = 88) received mTOR inhibitor (mTORi)-free, calcineurin inhibitor (CNI)-based versus sirolimus-based immunosuppression (group B: n = 78). We found no significant difference regarding HCV-RNA titers between group A and B. Since no effect in group B could be due to variable sirolimus dosing, we split group B into patients receiving sirolimus-based immunosuppression + CNIs for >50% (B1; n = 44) or <50% (B2; n = 34) of the time. While there remained no difference in HCV-RNA titer between groups, HCC recurrence-free survival in group B1 (81.8%) was markedly better versus both group A (62.7%; P = 0.0136) and group B2 (64.7%; P = 0.0326); Interestingly, further subgroup analysis revealed an increase (P = 0.0012) in liver enzyme values in group B2. Taken together, in HCV-infected patients with HCC and LTx, mTORi immunosuppression + CNIs yields excellent outcomes. Unexpectedly, higher levels of liver inflammation and poorer outcomes occur with mTORi monotherapy in the HCV+ subgroup.

Published
2020

8. Hepatocellular carcinoma progression during bridging before liver transplantation

Author

Renner P., Da Silva T., Schnitzbauer A. A., Verloh N., Schlitt H. J., Geissler E. K., Zulke C., Lamby P. E., Proneth A., Duvoux C., Burra P., Jauch K. -W., Rentsch M., Ganten T. M., Schmidt J., Settmacher U., Heise M., Rossi G., Cillo U., Kneteman N., Adam R., Van Hoek B., Bachellier P., Wolf P., Rostaing L., Bechstein W. O., Rizell M., Powell J., Hidalgo E., Gugenheim J., Wolters H., Brockmann J., Roy A., Mutzbauer I., Schlitt A., Beckebaum S., Graeb C., Nadalin S., Valente U., Sanchez Turrion V., Jamieson N., Scholz T., Colledan M., Fandrich F., Becker T., Soderdahl G., Chazouilleres O., Makisalo H., Pageaux G. -P., Steininger R., Soliman T., De Jong K. P., Pirenne J., Margreiter R., Pratschke J., Pinna A. D., Hauss J., Schreiber S., Strasser S., Klempnauer J., Troisi R. I., Bhoori S., Lerut J., Bilbao I., Klein C. G., Konigsrainer A., Otto G., Mazzaferro V., Neuhaus P., Renner, P, Da Silva, T, Schnitzbauer, A, Verloh, N, Schlitt, H, Geissler, E, Zulke, C, Lamby, P, Proneth, A, Duvoux, C, Burra, P, Jauch, K, Rentsch, M, Ganten, T, Schmidt, J, Settmacher, U, Heise, M, Rossi, G, Cillo, U, Kneteman, N, Adam, R, Van Hoek, B, Bachellier, P, Wolf, P, Rostaing, L, Bechstein, W, Rizell, M, Powell, J, Hidalgo, E, Gugenheim, J, Wolters, H, Brockmann, J, Roy, A, Mutzbauer, I, Schlitt, A, Beckebaum, S, Graeb, C, Nadalin, S, Valente, U, Sanchez Turrion, V, Jamieson, N, Scholz, T, Colledan, M, Fandrich, F, Becker, T, Soderdahl, G, Chazouilleres, O, Makisalo, H, Pageaux, G, Steininger, R, Soliman, T, De Jong, K, Pirenne, J, Margreiter, R, Pratschke, J, Pinna, A, Hauss, J, Schreiber, S, Strasser, S, Klempnauer, J, Troisi, R, Bhoori, S, Lerut, J, Bilbao, I, Klein, C, Konigsrainer, A, Otto, G, Mazzaferro, V, Neuhaus, P, and Publica

Subjects
Male, Carcinoma, Hepatocellular, Time Factor, Waiting Lists, AcademicSubjects/MED00910, Prognosi, Risk Factor, Middle Aged, Liver Transplantation, Treatment Outcome, Liver Neoplasm, Disease Progression, Female, Original Article, Survival Analysi, Neoplasm Recurrence, Local, AcademicSubjects/MED00010, Multivariate Analysi, Human
Abstract

Background Recipient selection for liver transplantation in hepatocellular carcinoma (HCC) is based primarily on criteria affecting the chance of long-term success. Here, the relationship between pretransplant bridging therapy and long-term survival was investigated in a subgroup analysis of the SiLVER Study. Methods Response to bridging, as defined by comparison of imaging at the time of listing and post-transplant pathology report, was categorized into controlled versus progressive disease (more than 20 per cent tumour growth or development of new lesions). Results Of 525 patients with HCC who had liver transplantation, 350 recipients underwent pretransplant bridging therapy. Tumour progression despite bridging was an independent risk factor affecting overall survival (hazard ratio 1.80; P = 0.005). For patients within the Milan criteria (MC) at listing, mean overall survival was longer for those with controlled versus progressive disease (6.8 versus 5.8 years; P

Published
2021

28. Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial

Author

Geissler, E, Schnitzbauer, A, Zulke, C, Lamby, P, Proneth, A, Duvoux, C, Burra, P, Jauch, K, Rentsch, M, Ganten, T, Schmidt, J, Settmacher, U, Heise, M, Rossi, G, Cillo, U, Kneteman, N, Adam, R, van Hoek, B, Bachellier, P, Wolf, P, Rostaing, L, Bechstein, W, Rizell, M, Powell, J, Hidalgo, E, Gugenheim, J, Wolters, H, Brockmann, J, Roy, A, Mutzbauer, I, Schlitt, A, Beckebaum, S, Graeb, C, Nadalin, S, Valente, U, Turrion, V, Jamieson, N, Scholz, T, Colledan, M, Fandrich, F, Becker, T, Soderdahl, G, Chazouilleres, O, Makisalo, H, Pageaux, G, Steininger, R, Soliman, T, de Jong, K, Pirenne, J, Margreiter, R, Pratschke, J, Pinna, A, Hauss, J, Schreiber, S, Strasser, S, Klempnauer, J, Troisi, R, Bhoori, S, Lerut, J, Bilbao, I, Klein, C, Konigsrainer, A, Mirza, D, Otto, G, Mazzaferro, V, Neuhaus, P, Schlitt, H, Geissler EK, Schnitzbauer AA, Zulke C, Lamby PE, Proneth A, Duvoux C, Burra P, Jauch KW, Rentsch M, Ganten TM, Schmidt J, Settmacher U, Heise M, Rossi G, Cillo U, Kneteman N, Adam R, van Hoek B, Bachellier P, Wolf P, Rostaing L, Bechstein WO, Rizell M, Powell J, Hidalgo E, Gugenheim J, Wolters H, Brockmann J, Roy A, Mutzbauer I, Schlitt A, Beckebaum S, Graeb C, Nadalin S, Valente U, Turrion VS, Jamieson N, Scholz T, Colledan M, Fandrich F, Becker T, Soderdahl G, Chazouilleres O, Makisalo H, Pageaux GP, Steininger R, Soliman T, de Jong KP, Pirenne J, Margreiter R, Pratschke J, Pinna AD, Hauss J, Schreiber S, Strasser S, Klempnauer J, Troisi RI, Bhoori S, Lerut J, Bilbao I, Klein CG, Konigsrainer A, Mirza DF, Otto G, Mazzaferro V, Neuhaus P, Schlitt HJ, Geissler, E, Schnitzbauer, A, Zulke, C, Lamby, P, Proneth, A, Duvoux, C, Burra, P, Jauch, K, Rentsch, M, Ganten, T, Schmidt, J, Settmacher, U, Heise, M, Rossi, G, Cillo, U, Kneteman, N, Adam, R, van Hoek, B, Bachellier, P, Wolf, P, Rostaing, L, Bechstein, W, Rizell, M, Powell, J, Hidalgo, E, Gugenheim, J, Wolters, H, Brockmann, J, Roy, A, Mutzbauer, I, Schlitt, A, Beckebaum, S, Graeb, C, Nadalin, S, Valente, U, Turrion, V, Jamieson, N, Scholz, T, Colledan, M, Fandrich, F, Becker, T, Soderdahl, G, Chazouilleres, O, Makisalo, H, Pageaux, G, Steininger, R, Soliman, T, de Jong, K, Pirenne, J, Margreiter, R, Pratschke, J, Pinna, A, Hauss, J, Schreiber, S, Strasser, S, Klempnauer, J, Troisi, R, Bhoori, S, Lerut, J, Bilbao, I, Klein, C, Konigsrainer, A, Mirza, D, Otto, G, Mazzaferro, V, Neuhaus, P, Schlitt, H, Geissler EK, Schnitzbauer AA, Zulke C, Lamby PE, Proneth A, Duvoux C, Burra P, Jauch KW, Rentsch M, Ganten TM, Schmidt J, Settmacher U, Heise M, Rossi G, Cillo U, Kneteman N, Adam R, van Hoek B, Bachellier P, Wolf P, Rostaing L, Bechstein WO, Rizell M, Powell J, Hidalgo E, Gugenheim J, Wolters H, Brockmann J, Roy A, Mutzbauer I, Schlitt A, Beckebaum S, Graeb C, Nadalin S, Valente U, Turrion VS, Jamieson N, Scholz T, Colledan M, Fandrich F, Becker T, Soderdahl G, Chazouilleres O, Makisalo H, Pageaux GP, Steininger R, Soliman T, de Jong KP, Pirenne J, Margreiter R, Pratschke J, Pinna AD, Hauss J, Schreiber S, Strasser S, Klempnauer J, Troisi RI, Bhoori S, Lerut J, Bilbao I, Klein CG, Konigsrainer A, Mirza DF, Otto G, Mazzaferro V, Neuhaus P, and Schlitt HJ

Abstract

Background.We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods. In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-To-Treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Results. Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most fromsirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Conclusions. Sirolimus in LTx recipients with HCC does not improve long-Term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.

Published
2016

35. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report

Author

Clavien, Pa, Lesurtel, M, Bossuyt, Pm, Gores, Gj, Langer, B, Perrier, A, OLT for HCC Consensus Group Abecassis, M, Balabaud, C, Barritt, Gj, Belghiti, J, Bhoori, S, Bossuyt, P, Breitenstein, S, Broelsch, C, Bruix, J, Burra, Patrizia, Burroughs, A, Busuttil, R, Charlton, M, Cherqui, D, Colombo, Ml, D'Albuquerque, C, D'Alessandro, A, de Santibañez EJ, Dufour, F, Durand, F, Dutkowski, P, Duvoux, C, El Serag, H, Fan, St, Finn, Rs, Fisher, R, Forner, A, Freeman, R, Fung, J, Geier, A, Germani, G, Gores, G, Gouw, As, Grant, D, Greig, P, Gurusamy, K, Hanto, D, Heaton, N, Heim, M, Hemming, A, Hippen, B, Hisham, A, Hubscher, S, Ichida, T, Kahn, D, Kew, M, Kita, Y, Kiuchi, T, Klintmalm, Gb, Kneteman, N, Kojiro, M, Kudo, M, Lee, Jm, Lee, Sg, Lencioni, R, Lerut, J, Livraghi, T, Llovet, J, Lo, Cm, Lodge, P, Maccaughan, G, Madoff, D, Majno, P, Marcellin, P, Marrero, J, Mazzaferro, V, Mergental, H, Merle, P, Miksad, R, Mornex, F, Müllhaupt, B, Olthoff, K, Paradis, V, Pestalozzi, B, Pomfret, E, Poon, R, Porte, R, Prasad, Kr, Raptis, D, Roskams, T, Rossi, M, Samuel, D, Schlitt, H, Schwartz, M, Sexton Dobby AM, Shaked, A, Sherman, M, Siegler, M, Suh, Ks, Todo, S, Toso, C, Trevisani, F, Trotter, Jj, Valdecasas, Gj, Vauthey, N, Vilgrain, V, Villamil, F, Vonlanthen, R, Wald, C, Weber, A, Wiesner, R, Wright, L, Yao, F, Zheng, Ss, Zucman Rossi, J., P.A.Clavien, M. Lesurtel, P.M. Bossuyt, G.J. Gore, B. Langer, A. Perrier, on behalf of the OLT for HCC Consensus Group […, F. Trevisani, and …]

Subjects
medicine.medical_specialty, Carcinoma, Hepatocellular, Waiting Lists, medicine.medical_treatment, media_common.quotation_subject, MEDLINE, 030230 surgery, Liver transplantation, Milan criteria, Risk Assessment, Article, RECOMMENDATIONS, 03 medical and health sciences, 0302 clinical medicine, Jury, Risk Factors, Liver Neoplasms/mortality/surgery, medicine, hepatocellular carcinoma, liver transplantation, Humans, HEPATOCELLULAR CARCINOMA, Hepatocellular/mortality/surgery, Tissue Donors/supply & distribution, media_common, ddc:616, Evidence-Based Medicine, business.industry, Patient Selection, Liver Neoplasms, Carcinoma, LIVER TRANSPLANTATION, Evidence-based medicine, medicine.disease, Tissue Donors, Neoadjuvant Therapy, 3. Good health, Surgery, Treatment Outcome, Oncology, Family medicine, Donation, Hepatocellular carcinoma, Liver Transplantation/adverse effects/mortality/standards, 030211 gastroenterology & hepatology, Working group, business
Abstract

Although liver transplantation is a widely accepted treatment for hepatocellular carcinoma (HCC), much controversy remains and there is no generally accepted set of guidelines. An international consensus conference was held on Dec 2–4, 2010, in Zurich, Switzerland, with the aim of reviewing current practice regarding liver transplantation in patients with HCC and to develop internationally accepted statements and guidelines. The format of the conference was based on the Danish model. 19 working groups of experts prepared evidence-based reviews according to the Oxford classification, and drafted recommendations answering 19 specific questions. An independent jury of nine members was appointed to review these submissions and make final recommendations, after debates with the experts and audience at the conference. This report presents the final 37 statements and recommendations, covering assessment of candidates for liver transplantation, criteria for listing in cirrhotic and non-cirrhotic patients, role of tumour downstaging, management of patients on the waiting list, role of living donation, and post-transplant management.

Published
2012
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36. “Very early” intrahepatic cholangiocarcinoma may become an acceptable indication for liver transplantation. A multicenter validation study

Author

Sapisochin, G., primary, Facciuto, M., additional, Mehta, N., additional, Vibert, E., additional, Hernandez-Alejandro, R., additional, Pinna, A.D., additional, Hwang, S., additional, Agopian, V.G., additional, Gores, G., additional, Reyes, J., additional, Soubrane, O., additional, Reichman, T., additional, Kim, P., additional, Sposito, C., additional, Clavien, P.A., additional, Toso, C., additional, Kneteman, N., additional, and Bruix, J., additional

Published
2016
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37. Once-daily prolonged-release Tacrolimus (ADVAGRAF) versus twice-daily Tacrolimus (PROGRAF) in liver transplantation

Author

Trunecka, P, Boillot, O, Seehofer, D, Pinna, Ad, Fischer, L, Ericzon, Bg, Troisi, Ri, Baccarani, U, ORTIZ DE URBINA, J, Wall, W, Mccaughan, G, Jones, R, DE ROOVER, A, Mies, S, Moreira, L, Lima, A, Cantisani, G, Kneteman, N, Grant, D, Roy, A, Scudamore, C, Tchervenkov, J, Clavien, P, Candinas, D, Schmidt, J, Schlitt, J, Bilbao, I, Charco, R, Pera, C, Bernardos, A, MIR PALLARDO, J, Varo, E, Isoniemi, H, Rostaing, L, Samuel, D, Pageaux, G, Durand, F, Duvoux, C, Boudjema, K, Wolf, P, Burroughs, A, O' GRADY, J, Prasad, R, Manas, D, Mccormick, A, Colledan, M, Valente, Umberto, Gerunda, G, Gridelli, B, Bentdal, O, Munn, S, Paczek, L, Bäckman, L., Trunecka P., Boillot O., Seehofer D., Pinna A.D., Fischer L., Ericzon B.G., Troisi R.I., Baccarani U., Ortiz de Urbina J., Wall W., and Tacrolimus Prolonged Release Liver Study Group

Subjects
Adult, Graft Rejection, Male, medicine.medical_specialty, Randomization, medicine.medical_treatment, Urology, chemical and pharmacologic phenomena, Liver transplantation, Kidney Function Tests, Tacrolimus, Daclizumab, medicine, Humans, Immunology and Allergy, Pharmacology (medical), Adverse effect, Antibacterial agent, Transplantation, Protein synthesis inhibitor, business.industry, tacrolimu, Middle Aged, Liver Transplantation, Surgery, Multicenter Study, Calcineurin, Treatment Outcome, surgical procedures, operative, Randomized Controlled Trial, Immunosuppression, Steroids, RCT, Female, business, Immunosuppressive Agents, medicine.drug
Abstract

The efficacy and safety of dual-therapy regimens of twice-daily tacrolimus (BID; Prograf) and once-daily tacrolimus (QD; Advagraf) administered with steroids, without antibody induction, were compared in a multicenter, 1:1-randomized, two-arm, parallel-group study in 475 primary liver transplant recipients. A double-blind, double-dummy 24-week period was followed by an open extension to 12 months posttransplant. The primary endpoint, event rate of biopsy-proven acute rejection (BPAR) at 24 weeks, was 33.7% for tacrolimus BID versus 36.3% for tacrolimus QD (Per-protocol set; p = 0.512; treatment difference 2.6%, 95% confidence interval -7.3%, 12.4%), falling within the predefined 15% noninferiority margin. At 12 months, BPAR episodes requiring treatment were similar for tacrolimus BID and QD (28.1% and 24.7%). Twelve-month patient and graft survival was 90.8% and 85.6% for tacrolimus BID and 89.2% and 85.3% for tacrolimus QD. Adverse event (AE) profiles were similar for both tacrolimus BID and QD with comparable incidences of AEs and serious AEs. Tacrolimus QD was well tolerated with similar efficacy and safety profiles to tacrolimus BID.

Published
2010

38. The 3rd Canadian symposium on Hepatitis c Virus: Expanding care in the interferon-free era

Author

MacParland, SA, Bilodeau, M, Grebely, J, Bruneau, J, Cooper, C, Klein, M, Sagan, SM, Choucha, N, Balfour, L, Bialystok, F, Krajden, M, Raven, J, Roberts, E, Russell, R, Houghton, M, Tyrrell, DL, Feld, JJ, Butt, G, Conway, B, Edwards, A, Fischer, B, Götte, M, Kneteman, N, Krahn, M, Levy, G, Liu, Q, McGilvray, I, Michalak, T, Mugford, G, Myers, R, Ostrowski, M, Pause, A, Pezacki, J, Richardson, C, Schang, L, Shoukry, N, Sonenberg, N, Soudeyns, H, Tellier, R, Tyndall, M, Wilson, J, Boisvert, M, Depla, M, Dupont, B, Ehteshami, M, Issur, M, Olmstead, A, Sarhan, M, Siu, R, Van Buuren, N, Ablenas, C, Bernier, A, Cunningham, E, Fabre, T, Fahmy, A, Hoffman, B, Hyrina, A, Kofahi, H, Kulkarni, A, Moqueet, N, Ardakan, NN, Singaravelu, R, Thibault, P, Wu, Q, Artenie, A, Puzhko, S, Saeed, S, Taylor, N, Wong, J, Cumming, A, MacParland, SA, Bilodeau, M, Grebely, J, Bruneau, J, Cooper, C, Klein, M, Sagan, SM, Choucha, N, Balfour, L, Bialystok, F, Krajden, M, Raven, J, Roberts, E, Russell, R, Houghton, M, Tyrrell, DL, Feld, JJ, Butt, G, Conway, B, Edwards, A, Fischer, B, Götte, M, Kneteman, N, Krahn, M, Levy, G, Liu, Q, McGilvray, I, Michalak, T, Mugford, G, Myers, R, Ostrowski, M, Pause, A, Pezacki, J, Richardson, C, Schang, L, Shoukry, N, Sonenberg, N, Soudeyns, H, Tellier, R, Tyndall, M, Wilson, J, Boisvert, M, Depla, M, Dupont, B, Ehteshami, M, Issur, M, Olmstead, A, Sarhan, M, Siu, R, Van Buuren, N, Ablenas, C, Bernier, A, Cunningham, E, Fabre, T, Fahmy, A, Hoffman, B, Hyrina, A, Kofahi, H, Kulkarni, A, Moqueet, N, Ardakan, NN, Singaravelu, R, Thibault, P, Wu, Q, Artenie, A, Puzhko, S, Saeed, S, Taylor, N, Wong, J, and Cumming, A

Abstract

Hepatitis C virus (HCV) currently infects approximately 250,000 individuals in Canada and causes more years of life lost than any other infectious disease in the country. In August 2011, new therapies were approved by Health Canada that have achieved higher response rates among those treated, but are poorly tolerated. By 2014/2015, shortcourse, well-tolerated treatments with cure rates >95% will be available. However, treatment uptake is poor due to structural, financial, geographical, cultural and social barriers. As such, 'Barriers to access to HCV care in Canada' is a crucial topic that must be addressed to decrease HCV disease burden and potentially eliminate HCV in Canada. Understanding how to better care for HCV-infected individuals requires integration across multiple disciplines including researchers, clinical services and policy makers to address the major populations affected by HCV including people who inject drugs, baby boomers, immigrants and Aboriginal and/or First Nations people. In 2012, the National CIHR Research Training Program in Hepatitis C organized the 1st Canadian Symposium on Hepatitis C Virus (CSHCV) in Montreal, Quebec. The 2nd CSHCV was held in 2013 in Victoria, British Columbia. Both symposia were highly successful, attracting leading international faculty with excellent attendance leading to dialogue and knowledge translation among attendees of diverse backgrounds. The current article summarizes the 3rd CSHCV, held February 2014, in Toronto, Ontario.

Published
2014

40. Novel approaches toward early diagnosis of islet allograft rejection

Author

Shapiro, A. M. J., Hao, E. G., Lakey, J. R. T., Yakimets, W. J., Churchill, T. A., Mitlianga, P. G., George K Papadopoulos, Elliott, J. F., Rajotte, R. V., and Kneteman, N. M.

Subjects
Male, Islets of Langerhans/physiopathology, beta-Galactosidase/blood, Islets of Langerhans Transplantation, Rats, Inbred WF, Glucose Tolerance Test, Rats, Dogs, Rats, Inbred Lew, Graft Rejection/blood/*diagnosis, Isoenzymes/blood, Animals, Transplantation, Homologous, Diabetes Mellitus, Experimental/physiopathology/surgery, Biological Markers/blood, Glutamate Decarboxylase/blood
Abstract

BACKGROUND: The inability to diagnose early rejection of an islet allograft has previously proved to be a major impediment to progress in clinical islet transplantation. The need to detect early rejection will become even more relevant as new tolerance-inducing protocols are evaluated in the clinic. We explored three novel approaches toward development of early diagnostic markers of islet rejection after islet allotransplantation. METHODS: (a) Canine islet allograft transplant recipients were immunosuppressed for 1 month, then therapy was withdrawn. Serum glutamic acid decarboxylase antigen (GAD65), an endogenous islet protein, was monitored daily with a CO2 release assay. (b) Rodent islets were genetically engineered to express a unique foreign protein (beta-galactosidase) by using adenoviral vectors, and after allograft transplantation, the viral-specific protein was measured in serum using optical luminescence. (c) Rodents receiving islet allografts were immunosuppressed temporarily, and daily glucose tolerance tests were followed until graft failure occurred. RESULTS: (a) Although serum monitoring of GAD65 antigen demonstrated elevated levels preceding loss of graft function in preliminary studies, the effect was not reproducible in all animals. (b) Genetically engineered rodent islets demonstrated normal insulin kinetics in vitro (insulin stimulation index 2.57+/-0.2 vs. 2.95+/-0.3 for control islets, P=ns), and purified viral protein products had a stable half-life of 8 hr in vivo. After islet allotransplantation, there were two peak elevations in serum viral proteins, confirming that an intra-islet "sentinel signal" could be detected serologically during acute rejection. There was no lead-time ahead of hyperglycemia, however. (c) Daily sequential intravenous glucose tolerance (IVGT) tests demonstrated evidence of allograft dysfunction (decline in KG) with a 2-day lead time to hyperglycemia (2.58+/-0.3 vs. 1.63+/-0.2%/min, respectively, P

Published
2001

41. A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma

Author

Schnitzbauer, A, Zuelke, C, Graeb, C, Rochon, J, Bilbao, I, Burra, P, de Jong, K, Duvoux, C, Kneteman, N, Adam, R, Bechstein, W, Becker, T, Beckebaum, S, Chazouilleres, O, Cillo, U, Colledan, M, Fandrich, F, Gugenheim, J, Hauss, J, Heise, M, Hidalgo, E, Jamieson, N, Konigsrainer, A, Lamby, P, Lerut, J, Makisalo, H, Margreiter, R, Mazzaferro, V, Mutzbauer, I, Otto, G, Pageaux, G, Pinna, A, Pirenne, J, Rizell, M, Rossi, G, Rostaing, L, Roy, A, Turrion, V, Schmidt, J, Troisi, R, van Hoek, B, Valente, U, Wolf, P, Wolters, H, Mirza, D, Scholz, T, Steininger, R, Soderdahl, G, Strasser, S, Jauch, K, Neuhaus, P, Schlitt, H, Geissler, E, Schnitzbauer AA, Zuelke C, Graeb C, Rochon J, Bilbao I, Burra P, de Jong KP, Duvoux C, Kneteman NM, Adam R, Bechstein WO, Becker T, Beckebaum S, Chazouilleres O, Cillo U, Colledan M, Fandrich F, Gugenheim J, Hauss JP, Heise M, Hidalgo E, Jamieson N, Konigsrainer A, Lamby PE, Lerut JP, Makisalo H, Margreiter R, Mazzaferro V, Mutzbauer I, Otto G, Pageaux GP, Pinna AD, Pirenne J, Rizell M, Rossi G, Rostaing L, Roy A, Turrion VS, Schmidt J, Troisi RI, van Hoek B, Valente U, Wolf P, Wolters H, Mirza DF, Scholz T, Steininger R, Soderdahl G, Strasser SI, Jauch KW, Neuhaus P, Schlitt HJ, Geissler EK, Schnitzbauer, A, Zuelke, C, Graeb, C, Rochon, J, Bilbao, I, Burra, P, de Jong, K, Duvoux, C, Kneteman, N, Adam, R, Bechstein, W, Becker, T, Beckebaum, S, Chazouilleres, O, Cillo, U, Colledan, M, Fandrich, F, Gugenheim, J, Hauss, J, Heise, M, Hidalgo, E, Jamieson, N, Konigsrainer, A, Lamby, P, Lerut, J, Makisalo, H, Margreiter, R, Mazzaferro, V, Mutzbauer, I, Otto, G, Pageaux, G, Pinna, A, Pirenne, J, Rizell, M, Rossi, G, Rostaing, L, Roy, A, Turrion, V, Schmidt, J, Troisi, R, van Hoek, B, Valente, U, Wolf, P, Wolters, H, Mirza, D, Scholz, T, Steininger, R, Soderdahl, G, Strasser, S, Jauch, K, Neuhaus, P, Schlitt, H, Geissler, E, Schnitzbauer AA, Zuelke C, Graeb C, Rochon J, Bilbao I, Burra P, de Jong KP, Duvoux C, Kneteman NM, Adam R, Bechstein WO, Becker T, Beckebaum S, Chazouilleres O, Cillo U, Colledan M, Fandrich F, Gugenheim J, Hauss JP, Heise M, Hidalgo E, Jamieson N, Konigsrainer A, Lamby PE, Lerut JP, Makisalo H, Margreiter R, Mazzaferro V, Mutzbauer I, Otto G, Pageaux GP, Pinna AD, Pirenne J, Rizell M, Rossi G, Rostaing L, Roy A, Turrion VS, Schmidt J, Troisi RI, van Hoek B, Valente U, Wolf P, Wolters H, Mirza DF, Scholz T, Steininger R, Soderdahl G, Strasser SI, Jauch KW, Neuhaus P, Schlitt HJ, and Geissler EK

Abstract

Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC.Methods/Design: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 21/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating.Discussion: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to p

Published
2010

46. Preliminary Single‐Center Canadian Experience of Human Normothermic Ex VivoLiver Perfusion: Results of a Clinical Trial

Author

Bral, M., Gala‐Lopez, B., Bigam, D., Kneteman, N., Malcolm, A., Livingstone, S., Andres, A., Emamaullee, J., Russell, L., Coussios, C., West, L. J., Friend, P. J., and Shapiro, A. M. J.

Abstract

After extensive experimentation, outcomes of a first clinical normothermic machine perfusion (NMP) liver trial in the United Kingdom demonstrated feasibility and clear safety, with improved liver function compared with standard static cold storage (SCS). We present a preliminary single‐center North American experience using identical NMPtechnology. Ten donor liver grafts were procured, four (40%) from donation after circulatory death (DCD), of which nine were transplanted. One liver did not proceed because of a technical failure with portal cannulation and was discarded. Transplanted NMPgrafts were matched 1:3 with transplanted SCSlivers. Median NMPwas 11.5 h (range 3.3–22.5 h) with one DCDliver perfused for 22.5 h. All transplanted livers functioned, and serum transaminases, bilirubin, international normalized ratio, and lactate levels corrected in NMPrecipients similarly to controls. Graft survival at 30 days (primary outcome) was not statistically different between groups on an intent‐to‐treat basis (p = 0.25). Intensive care and hospital stays were significantly more prolonged in the NMPgroup. This preliminary experience demonstrates feasibility as well as potential technical risks of NMPin a North American setting and highlights a need for larger, randomized studies. This paper describes a preliminary Canadian single‐center experience with clinical ex vivonormothermic liver perfusion and transplantation. See the video at amjtransplant.com/videos.

Published
2017
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47. ALEMTUZUMAB INDUCTION AND TAC/MMF MAINTENANCE SUBSTANTIALLY IMPROVES LONG TERM INSULIN INDEPENDENCE RATES AFTER CLINICAL ISLET TRANSPLANTATION, AND STRONGLY SUPPRESSES BOTH AUTO AND ALLOREACTIVITY

Author

Shapiro, A. M.J., primary, Toso, C., additional, Koh, A., additional, Calne, S. R., additional, Kin, T., additional, OʼGorman, D., additional, Malcolm, A., additional, Dinyari, P., additional, Imes, S., additional, Owen, R., additional, Kneteman, N. M., additional, Bigam, D., additional, Senior, P., additional, and Roep, B., additional

Published
2010
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