Early chimerism after liver transplantation reflects the clinical course of recurrent hepatitis C

Masashi Utsumi, Akinobu Takaki, Yuzo Umeda, Kazuko Koike, Stephanie C. Napier, Nobukazu Watanabe, Susumu Shinoura, Ryuichi Yoshida, Daisuke Nobuoka, Tetsuya Yasunaka, Takahiro Oto, Motoo Araki, Kazuhide Yamamoto, Toshiyoshi Fujiwara, Takahito Yagi

Research output: Contribution to journalArticle

Abstract

Background: Human leukocyte antigen (HLA) mismatch is a characteristic feature of post-orthotopic liver transplantation (OLT) hepatitis C. To investigate the importance of donor HLA-restricted immune cells in post-OLT hepatitis C recurrence, we analyzed the frequency of donor chimerism and the clinical course of post-OLT hepatitis C. Material/Methods: We analyzed peripheral blood chimerism in 11 HCV-reinfected patients with post-HLA mismatched OLT. Patients were divided into 2 groups: the OLT chronic hepatitis C (CHC) group (n=8), exhibiting active hepatitis C recurrence; and the OLT-persistently normal ALT (PNALT) group (n=3), without active hepatitis. Chimerism was analyzed by flow cytometry using donor-specific anti-HLA antibodies in peripheral blood mononuclear cells from 1–100 days after OLT. Kidney (n=7) and lung (n=7) transplant recipients were also analyzed for comparison. As immune cells from the donor liver might contribute to post-OLT chimerism, the characteristics of perfusates from donor livers (n=10) were analyzed and defined. Results: Donor-derived cells were frequently observed in liver and lung transplant recipients. The frequency of donor-derived cells from the B cell subset was significantly higher in peripheral blood from OLT-CHC group than in that of the OLT-PNALT group. B cells, however, were not the predominant subset in the perfusates, indicating that inflow of donor-derived cells alone did not cause the chimerism. Conclusions: Chimerism of B cells is frequent in liver transplant patients with early recurrence of hepatitis C. We propose that monitoring of early chimerism could facilitate early detection of chronic hepatitis C recurrence, although we need more cases to investigate.

Original languageEnglish
Pages (from-to)156-165
Number of pages10
JournalAnnals of Transplantation
Volume22
DOIs
Publication statusPublished - 2017

Fingerprint

Chimerism
Hepatitis C
Liver Transplantation
Tissue Donors
HLA Antigens
Chronic Hepatitis C
Recurrence
Liver
B-Lymphocytes
B-Lymphocyte Subsets
Lung
Hepatitis
Blood Cells
Flow Cytometry
Transplants
Kidney

Keywords

  • B-Lymphocytes
  • Chimerism
  • Chronic
  • Hepatitis
  • Liver Transplantation

ASJC Scopus subject areas

  • Transplantation

Cite this

Early chimerism after liver transplantation reflects the clinical course of recurrent hepatitis C. / Utsumi, Masashi; Takaki, Akinobu; Umeda, Yuzo; Koike, Kazuko; Napier, Stephanie C.; Watanabe, Nobukazu; Shinoura, Susumu; Yoshida, Ryuichi; Nobuoka, Daisuke; Yasunaka, Tetsuya; Oto, Takahiro; Araki, Motoo; Yamamoto, Kazuhide; Fujiwara, Toshiyoshi; Yagi, Takahito.

In: Annals of Transplantation, Vol. 22, 2017, p. 156-165.

Research output: Contribution to journalArticle

@article{a3573aaa7cd7499e9559d0096e4c2c0f,
title = "Early chimerism after liver transplantation reflects the clinical course of recurrent hepatitis C",
abstract = "Background: Human leukocyte antigen (HLA) mismatch is a characteristic feature of post-orthotopic liver transplantation (OLT) hepatitis C. To investigate the importance of donor HLA-restricted immune cells in post-OLT hepatitis C recurrence, we analyzed the frequency of donor chimerism and the clinical course of post-OLT hepatitis C. Material/Methods: We analyzed peripheral blood chimerism in 11 HCV-reinfected patients with post-HLA mismatched OLT. Patients were divided into 2 groups: the OLT chronic hepatitis C (CHC) group (n=8), exhibiting active hepatitis C recurrence; and the OLT-persistently normal ALT (PNALT) group (n=3), without active hepatitis. Chimerism was analyzed by flow cytometry using donor-specific anti-HLA antibodies in peripheral blood mononuclear cells from 1–100 days after OLT. Kidney (n=7) and lung (n=7) transplant recipients were also analyzed for comparison. As immune cells from the donor liver might contribute to post-OLT chimerism, the characteristics of perfusates from donor livers (n=10) were analyzed and defined. Results: Donor-derived cells were frequently observed in liver and lung transplant recipients. The frequency of donor-derived cells from the B cell subset was significantly higher in peripheral blood from OLT-CHC group than in that of the OLT-PNALT group. B cells, however, were not the predominant subset in the perfusates, indicating that inflow of donor-derived cells alone did not cause the chimerism. Conclusions: Chimerism of B cells is frequent in liver transplant patients with early recurrence of hepatitis C. We propose that monitoring of early chimerism could facilitate early detection of chronic hepatitis C recurrence, although we need more cases to investigate.",
keywords = "B-Lymphocytes, Chimerism, Chronic, Hepatitis, Liver Transplantation",
author = "Masashi Utsumi and Akinobu Takaki and Yuzo Umeda and Kazuko Koike and Napier, {Stephanie C.} and Nobukazu Watanabe and Susumu Shinoura and Ryuichi Yoshida and Daisuke Nobuoka and Tetsuya Yasunaka and Takahiro Oto and Motoo Araki and Kazuhide Yamamoto and Toshiyoshi Fujiwara and Takahito Yagi",
year = "2017",
doi = "10.12659/AOT.900494",
language = "English",
volume = "22",
pages = "156--165",
journal = "Annals of Transplantation",
issn = "1425-9524",
publisher = "International Scientific Information, Inc.",

}

TY - JOUR

T1 - Early chimerism after liver transplantation reflects the clinical course of recurrent hepatitis C

AU - Utsumi, Masashi

AU - Takaki, Akinobu

AU - Umeda, Yuzo

AU - Koike, Kazuko

AU - Napier, Stephanie C.

AU - Watanabe, Nobukazu

AU - Shinoura, Susumu

AU - Yoshida, Ryuichi

AU - Nobuoka, Daisuke

AU - Yasunaka, Tetsuya

AU - Oto, Takahiro

AU - Araki, Motoo

AU - Yamamoto, Kazuhide

AU - Fujiwara, Toshiyoshi

AU - Yagi, Takahito

PY - 2017

Y1 - 2017

N2 - Background: Human leukocyte antigen (HLA) mismatch is a characteristic feature of post-orthotopic liver transplantation (OLT) hepatitis C. To investigate the importance of donor HLA-restricted immune cells in post-OLT hepatitis C recurrence, we analyzed the frequency of donor chimerism and the clinical course of post-OLT hepatitis C. Material/Methods: We analyzed peripheral blood chimerism in 11 HCV-reinfected patients with post-HLA mismatched OLT. Patients were divided into 2 groups: the OLT chronic hepatitis C (CHC) group (n=8), exhibiting active hepatitis C recurrence; and the OLT-persistently normal ALT (PNALT) group (n=3), without active hepatitis. Chimerism was analyzed by flow cytometry using donor-specific anti-HLA antibodies in peripheral blood mononuclear cells from 1–100 days after OLT. Kidney (n=7) and lung (n=7) transplant recipients were also analyzed for comparison. As immune cells from the donor liver might contribute to post-OLT chimerism, the characteristics of perfusates from donor livers (n=10) were analyzed and defined. Results: Donor-derived cells were frequently observed in liver and lung transplant recipients. The frequency of donor-derived cells from the B cell subset was significantly higher in peripheral blood from OLT-CHC group than in that of the OLT-PNALT group. B cells, however, were not the predominant subset in the perfusates, indicating that inflow of donor-derived cells alone did not cause the chimerism. Conclusions: Chimerism of B cells is frequent in liver transplant patients with early recurrence of hepatitis C. We propose that monitoring of early chimerism could facilitate early detection of chronic hepatitis C recurrence, although we need more cases to investigate.

AB - Background: Human leukocyte antigen (HLA) mismatch is a characteristic feature of post-orthotopic liver transplantation (OLT) hepatitis C. To investigate the importance of donor HLA-restricted immune cells in post-OLT hepatitis C recurrence, we analyzed the frequency of donor chimerism and the clinical course of post-OLT hepatitis C. Material/Methods: We analyzed peripheral blood chimerism in 11 HCV-reinfected patients with post-HLA mismatched OLT. Patients were divided into 2 groups: the OLT chronic hepatitis C (CHC) group (n=8), exhibiting active hepatitis C recurrence; and the OLT-persistently normal ALT (PNALT) group (n=3), without active hepatitis. Chimerism was analyzed by flow cytometry using donor-specific anti-HLA antibodies in peripheral blood mononuclear cells from 1–100 days after OLT. Kidney (n=7) and lung (n=7) transplant recipients were also analyzed for comparison. As immune cells from the donor liver might contribute to post-OLT chimerism, the characteristics of perfusates from donor livers (n=10) were analyzed and defined. Results: Donor-derived cells were frequently observed in liver and lung transplant recipients. The frequency of donor-derived cells from the B cell subset was significantly higher in peripheral blood from OLT-CHC group than in that of the OLT-PNALT group. B cells, however, were not the predominant subset in the perfusates, indicating that inflow of donor-derived cells alone did not cause the chimerism. Conclusions: Chimerism of B cells is frequent in liver transplant patients with early recurrence of hepatitis C. We propose that monitoring of early chimerism could facilitate early detection of chronic hepatitis C recurrence, although we need more cases to investigate.

KW - B-Lymphocytes

KW - Chimerism

KW - Chronic

KW - Hepatitis

KW - Liver Transplantation

UR - http://www.scopus.com/inward/record.url?scp=85016163001&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016163001&partnerID=8YFLogxK

U2 - 10.12659/AOT.900494

DO - 10.12659/AOT.900494

M3 - Article

C2 - 28336908

AN - SCOPUS:85016163001

VL - 22

SP - 156

EP - 165

JO - Annals of Transplantation

JF - Annals of Transplantation

SN - 1425-9524

ER -