Rituximab induction to prevent the recurrence of PSC after liver transplantation—the lessons learned from ABO-incompatible living donor liver transplantation

Yohei Yamada, Ken Hoshino, Yasushi Fuchimoto, Kentaro Matsubara, Taizo Hibi, Hiroshi Yagi, Yuta Abe, Masahiro Shinoda, Minoru Kitago, Hideaki Obara, Takahito Yagi, Hideaki Okajima, Toshimi Kaido, Shinji Uemoto, Tatsuya Suzuki, Keiichi Kubota, Tomoharu Yoshizumi, Yoshihiko Maehara, Yukihiro Inomata, Yuko KitagawaHiroto Egawa, Tatsuo Kuroda

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Abstract

Background. Multiple studies have failed to reveal an effective method for preventing the recurrence of primary sclerosing cholangitis (PSC) after liver transplantation (LTx). A national study conducted in Japan revealed several risk factors for the recurrence after living donor LTx (LDLTx); however, recipients of ABO-blood type incompatible (ABO-I) LTx were excluded from the previous analysis. In the present study, we investigated the efficacy of an immunosuppressive protocol in ABO-I LTx on the recurrence of PSC after LDLTx. Methods. We conducted a national survey and analyzed the outcome of recipients who underwent ABO-I LDLTx for PSC (n = 12) between 1994 and 2010 in 9 centers and compared the outcome with that of ABO-compatible LDLTx for PSC (n = 96). The key elements of the immunosuppressive regimen in ABO-I LTx are plasma exchange sessions to remove existing antibodies, and the use of immunosuppression to control humoral immunity. Rituximab was added to the immunosuppression regimen from 2006 onward; 5 patients received rituximab perioperatively. Results. All 7 recipients who underwent ABO-I LDLTx before 2006 (who did not receive rituximab) died of infection (n = 3), antibody-mediated rejection (n = 1), ABO-incompatibility associated cholangiopathy (n = 1) or recurrence of PSC (n = 2). In contrast, we found that all 5 recipients from 2006 (who were treated with rituximab) retained an excellent graft function for more than 7 years without any recurrence of PSC. Conclusions. The findings of this study shed light on the efficacy of a novel strategy to prevent the recurrence of PSC and the possible mechanisms provided by rituximab treatment are discussed.

Original languageEnglish
Article numbere342
JournalTransplantation Direct
Volume4
Issue number2
DOIs
Publication statusPublished - Feb 2018

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Sclerosing Cholangitis
Living Donors
Liver Transplantation
Recurrence
Liver
Immunosuppressive Agents
Immunosuppression
Plasma Exchange
Antibodies
Humoral Immunity
Rituximab
Japan
Transplants
Infection

All Science Journal Classification (ASJC) codes

  • Transplantation

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Rituximab induction to prevent the recurrence of PSC after liver transplantation—the lessons learned from ABO-incompatible living donor liver transplantation. / Yamada, Yohei; Hoshino, Ken; Fuchimoto, Yasushi; Matsubara, Kentaro; Hibi, Taizo; Yagi, Hiroshi; Abe, Yuta; Shinoda, Masahiro; Kitago, Minoru; Obara, Hideaki; Yagi, Takahito; Okajima, Hideaki; Kaido, Toshimi; Uemoto, Shinji; Suzuki, Tatsuya; Kubota, Keiichi; Yoshizumi, Tomoharu; Maehara, Yoshihiko; Inomata, Yukihiro; Kitagawa, Yuko; Egawa, Hiroto; Kuroda, Tatsuo.

In: Transplantation Direct, Vol. 4, No. 2, e342, 02.2018.

Research output: Contribution to journalArticle

Yamada, Y, Hoshino, K, Fuchimoto, Y, Matsubara, K, Hibi, T, Yagi, H, Abe, Y, Shinoda, M, Kitago, M, Obara, H, Yagi, T, Okajima, H, Kaido, T, Uemoto, S, Suzuki, T, Kubota, K, Yoshizumi, T, Maehara, Y, Inomata, Y, Kitagawa, Y, Egawa, H & Kuroda, T 2018, 'Rituximab induction to prevent the recurrence of PSC after liver transplantation—the lessons learned from ABO-incompatible living donor liver transplantation', Transplantation Direct, vol. 4, no. 2, e342. https://doi.org/10.1097/TXD.0000000000000760
Yamada, Yohei ; Hoshino, Ken ; Fuchimoto, Yasushi ; Matsubara, Kentaro ; Hibi, Taizo ; Yagi, Hiroshi ; Abe, Yuta ; Shinoda, Masahiro ; Kitago, Minoru ; Obara, Hideaki ; Yagi, Takahito ; Okajima, Hideaki ; Kaido, Toshimi ; Uemoto, Shinji ; Suzuki, Tatsuya ; Kubota, Keiichi ; Yoshizumi, Tomoharu ; Maehara, Yoshihiko ; Inomata, Yukihiro ; Kitagawa, Yuko ; Egawa, Hiroto ; Kuroda, Tatsuo. / Rituximab induction to prevent the recurrence of PSC after liver transplantation—the lessons learned from ABO-incompatible living donor liver transplantation. In: Transplantation Direct. 2018 ; Vol. 4, No. 2.
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abstract = "Background. Multiple studies have failed to reveal an effective method for preventing the recurrence of primary sclerosing cholangitis (PSC) after liver transplantation (LTx). A national study conducted in Japan revealed several risk factors for the recurrence after living donor LTx (LDLTx); however, recipients of ABO-blood type incompatible (ABO-I) LTx were excluded from the previous analysis. In the present study, we investigated the efficacy of an immunosuppressive protocol in ABO-I LTx on the recurrence of PSC after LDLTx. Methods. We conducted a national survey and analyzed the outcome of recipients who underwent ABO-I LDLTx for PSC (n = 12) between 1994 and 2010 in 9 centers and compared the outcome with that of ABO-compatible LDLTx for PSC (n = 96). The key elements of the immunosuppressive regimen in ABO-I LTx are plasma exchange sessions to remove existing antibodies, and the use of immunosuppression to control humoral immunity. Rituximab was added to the immunosuppression regimen from 2006 onward; 5 patients received rituximab perioperatively. Results. All 7 recipients who underwent ABO-I LDLTx before 2006 (who did not receive rituximab) died of infection (n = 3), antibody-mediated rejection (n = 1), ABO-incompatibility associated cholangiopathy (n = 1) or recurrence of PSC (n = 2). In contrast, we found that all 5 recipients from 2006 (who were treated with rituximab) retained an excellent graft function for more than 7 years without any recurrence of PSC. Conclusions. The findings of this study shed light on the efficacy of a novel strategy to prevent the recurrence of PSC and the possible mechanisms provided by rituximab treatment are discussed.",
author = "Yohei Yamada and Ken Hoshino and Yasushi Fuchimoto and Kentaro Matsubara and Taizo Hibi and Hiroshi Yagi and Yuta Abe and Masahiro Shinoda and Minoru Kitago and Hideaki Obara and Takahito Yagi and Hideaki Okajima and Toshimi Kaido and Shinji Uemoto and Tatsuya Suzuki and Keiichi Kubota and Tomoharu Yoshizumi and Yoshihiko Maehara and Yukihiro Inomata and Yuko Kitagawa and Hiroto Egawa and Tatsuo Kuroda",
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T1 - Rituximab induction to prevent the recurrence of PSC after liver transplantation—the lessons learned from ABO-incompatible living donor liver transplantation

AU - Yamada, Yohei

AU - Hoshino, Ken

AU - Fuchimoto, Yasushi

AU - Matsubara, Kentaro

AU - Hibi, Taizo

AU - Yagi, Hiroshi

AU - Abe, Yuta

AU - Shinoda, Masahiro

AU - Kitago, Minoru

AU - Obara, Hideaki

AU - Yagi, Takahito

AU - Okajima, Hideaki

AU - Kaido, Toshimi

AU - Uemoto, Shinji

AU - Suzuki, Tatsuya

AU - Kubota, Keiichi

AU - Yoshizumi, Tomoharu

AU - Maehara, Yoshihiko

AU - Inomata, Yukihiro

AU - Kitagawa, Yuko

AU - Egawa, Hiroto

AU - Kuroda, Tatsuo

PY - 2018/2

Y1 - 2018/2

N2 - Background. Multiple studies have failed to reveal an effective method for preventing the recurrence of primary sclerosing cholangitis (PSC) after liver transplantation (LTx). A national study conducted in Japan revealed several risk factors for the recurrence after living donor LTx (LDLTx); however, recipients of ABO-blood type incompatible (ABO-I) LTx were excluded from the previous analysis. In the present study, we investigated the efficacy of an immunosuppressive protocol in ABO-I LTx on the recurrence of PSC after LDLTx. Methods. We conducted a national survey and analyzed the outcome of recipients who underwent ABO-I LDLTx for PSC (n = 12) between 1994 and 2010 in 9 centers and compared the outcome with that of ABO-compatible LDLTx for PSC (n = 96). The key elements of the immunosuppressive regimen in ABO-I LTx are plasma exchange sessions to remove existing antibodies, and the use of immunosuppression to control humoral immunity. Rituximab was added to the immunosuppression regimen from 2006 onward; 5 patients received rituximab perioperatively. Results. All 7 recipients who underwent ABO-I LDLTx before 2006 (who did not receive rituximab) died of infection (n = 3), antibody-mediated rejection (n = 1), ABO-incompatibility associated cholangiopathy (n = 1) or recurrence of PSC (n = 2). In contrast, we found that all 5 recipients from 2006 (who were treated with rituximab) retained an excellent graft function for more than 7 years without any recurrence of PSC. Conclusions. The findings of this study shed light on the efficacy of a novel strategy to prevent the recurrence of PSC and the possible mechanisms provided by rituximab treatment are discussed.

AB - Background. Multiple studies have failed to reveal an effective method for preventing the recurrence of primary sclerosing cholangitis (PSC) after liver transplantation (LTx). A national study conducted in Japan revealed several risk factors for the recurrence after living donor LTx (LDLTx); however, recipients of ABO-blood type incompatible (ABO-I) LTx were excluded from the previous analysis. In the present study, we investigated the efficacy of an immunosuppressive protocol in ABO-I LTx on the recurrence of PSC after LDLTx. Methods. We conducted a national survey and analyzed the outcome of recipients who underwent ABO-I LDLTx for PSC (n = 12) between 1994 and 2010 in 9 centers and compared the outcome with that of ABO-compatible LDLTx for PSC (n = 96). The key elements of the immunosuppressive regimen in ABO-I LTx are plasma exchange sessions to remove existing antibodies, and the use of immunosuppression to control humoral immunity. Rituximab was added to the immunosuppression regimen from 2006 onward; 5 patients received rituximab perioperatively. Results. All 7 recipients who underwent ABO-I LDLTx before 2006 (who did not receive rituximab) died of infection (n = 3), antibody-mediated rejection (n = 1), ABO-incompatibility associated cholangiopathy (n = 1) or recurrence of PSC (n = 2). In contrast, we found that all 5 recipients from 2006 (who were treated with rituximab) retained an excellent graft function for more than 7 years without any recurrence of PSC. Conclusions. The findings of this study shed light on the efficacy of a novel strategy to prevent the recurrence of PSC and the possible mechanisms provided by rituximab treatment are discussed.

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