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.
HCC recurrence in HCV-infected patients after liver transplantation: SiLVER Study reveals benefits of sirolimus in combination with CNIs – a post-hoc analysis / 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.; Bhoori, S.; Lerut, J.; Bilbao, I.; Klein, C. G.; Konigsrainer, A.; Otto, G.; Mazzaferro, V.; Neuhaus, P.. - In: TRANSPLANT INTERNATIONAL. - ISSN 0934-0874. - 33:8(2020), pp. 917-924. [10.1111/tri.13621]
HCC recurrence in HCV-infected patients after liver transplantation: SiLVER Study reveals benefits of sirolimus in combination with CNIs – a post-hoc analysis
Troisi R.Membro del Collaboration Group
;
2020
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
