Significance of C4d staining in ABO-identical/compatible liver transplantation

Hiromi Sakashita, Hironori Haga, Eishi Ashihara, Mei Chin Wen, Hiroaki Tsuji, Aya Miyagawa-Hayashino, Hiroto Egawa, Yasutsugu Takada, Taira Maekawa, Shinji Uemoto, Toshiaki Manabe

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Complement degradation product C4d has become an important marker of humoral or antibody-mediated rejection in renal and heart allograft biopsies. Although there have been several reports on the detection of C4d in liver allografts, the significance of C4d in liver transplantation and its relationship with humoral rejection are still not clear. We investigated the frequency and pattern of C4d staining in liver allograft biopsies with reference to preoperative lymphocyte crossmatch tests, which detect donor-reactive lymphocyte antibody. Survival rates at 5 years were 77% for crossmatch-negative patients and 53% for crossmatch-positive patients (P=0.009). In crossmatch-negative patients, reproducible positive staining was obtained in 28 of 86 (33%) biopsies taken within 90 days after transplantation and 33 of 96 (34%) biopsies 90 days or after transplantation. Most C4d staining was observed in the portal areas, and no clear correlation was observed between C4d positivity and histological diagnosis. In crossmatch-positive patients, 9 of 11 (82%) biopsies showed positivity for C4d. C4d stained perivenular areas as well as portal areas. Histology of crossmatch-positive patients included acute rejection and cholangitis, but did not include periportal changes that were seen in humoral rejection in ABO-incompatible liver transplantation. In summary, focal C4d deposition was seen in various types of liver allograft injury and had little clinical impact on crossmatch-negative patients, but extensive C4d staining in crossmatch-positive patients may be associated with humoral rejection and poor graft survival.

Original languageEnglish (US)
Pages (from-to)676-684
Number of pages9
JournalModern Pathology
Volume20
Issue number6
DOIs
StatePublished - Jun 1 2007

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Liver Transplantation
Staining and Labeling
Allografts
Biopsy
Liver
Transplantation
Lymphocytes
Cholangitis
Antibodies
Graft Survival
Histology
Survival Rate
Tissue Donors
Kidney
Wounds and Injuries

Keywords

  • C4d
  • Humoral rejection
  • Liver transplantation
  • Lymphocytotoxic crossmatch

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Sakashita, H., Haga, H., Ashihara, E., Wen, M. C., Tsuji, H., Miyagawa-Hayashino, A., ... Manabe, T. (2007). Significance of C4d staining in ABO-identical/compatible liver transplantation. Modern Pathology, 20(6), 676-684. https://doi.org/10.1038/modpathol.3800784

Significance of C4d staining in ABO-identical/compatible liver transplantation. / Sakashita, Hiromi; Haga, Hironori; Ashihara, Eishi; Wen, Mei Chin; Tsuji, Hiroaki; Miyagawa-Hayashino, Aya; Egawa, Hiroto; Takada, Yasutsugu; Maekawa, Taira; Uemoto, Shinji; Manabe, Toshiaki.

In: Modern Pathology, Vol. 20, No. 6, 01.06.2007, p. 676-684.

Research output: Contribution to journalArticle

Sakashita, H, Haga, H, Ashihara, E, Wen, MC, Tsuji, H, Miyagawa-Hayashino, A, Egawa, H, Takada, Y, Maekawa, T, Uemoto, S & Manabe, T 2007, 'Significance of C4d staining in ABO-identical/compatible liver transplantation', Modern Pathology, vol. 20, no. 6, pp. 676-684. https://doi.org/10.1038/modpathol.3800784
Sakashita H, Haga H, Ashihara E, Wen MC, Tsuji H, Miyagawa-Hayashino A et al. Significance of C4d staining in ABO-identical/compatible liver transplantation. Modern Pathology. 2007 Jun 1;20(6):676-684. https://doi.org/10.1038/modpathol.3800784
Sakashita, Hiromi ; Haga, Hironori ; Ashihara, Eishi ; Wen, Mei Chin ; Tsuji, Hiroaki ; Miyagawa-Hayashino, Aya ; Egawa, Hiroto ; Takada, Yasutsugu ; Maekawa, Taira ; Uemoto, Shinji ; Manabe, Toshiaki. / Significance of C4d staining in ABO-identical/compatible liver transplantation. In: Modern Pathology. 2007 ; Vol. 20, No. 6. pp. 676-684.
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abstract = "Complement degradation product C4d has become an important marker of humoral or antibody-mediated rejection in renal and heart allograft biopsies. Although there have been several reports on the detection of C4d in liver allografts, the significance of C4d in liver transplantation and its relationship with humoral rejection are still not clear. We investigated the frequency and pattern of C4d staining in liver allograft biopsies with reference to preoperative lymphocyte crossmatch tests, which detect donor-reactive lymphocyte antibody. Survival rates at 5 years were 77{\%} for crossmatch-negative patients and 53{\%} for crossmatch-positive patients (P=0.009). In crossmatch-negative patients, reproducible positive staining was obtained in 28 of 86 (33{\%}) biopsies taken within 90 days after transplantation and 33 of 96 (34{\%}) biopsies 90 days or after transplantation. Most C4d staining was observed in the portal areas, and no clear correlation was observed between C4d positivity and histological diagnosis. In crossmatch-positive patients, 9 of 11 (82{\%}) biopsies showed positivity for C4d. C4d stained perivenular areas as well as portal areas. Histology of crossmatch-positive patients included acute rejection and cholangitis, but did not include periportal changes that were seen in humoral rejection in ABO-incompatible liver transplantation. In summary, focal C4d deposition was seen in various types of liver allograft injury and had little clinical impact on crossmatch-negative patients, but extensive C4d staining in crossmatch-positive patients may be associated with humoral rejection and poor graft survival.",
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AU - Miyagawa-Hayashino, Aya

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