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Graft-Versus-Host Disease

Risk factors and prognosis of hepatic acute GvHD after allogeneic hematopoietic cell transplantation


Hepatic acute GvHD (aGvHD) is associated with high mortality owing to poor response to immunosuppressive therapy. The pathogenesis of hepatic aGvHD differs from that of other lesions, and specific risk factors related to pre-transplant liver conditions should be determined. We conducted a cohort study by using a Japanese transplant registry database (N=8378). Of these subjects, 1.5% had hepatitis C virus Ab (HCV-Ab) and 9.4% had liver dysfunction (elevated transaminase or bilirubin levels) before hematopoietic cell transplantation (HCT). After HCT, the cumulative incidence of hepatic aGvHD was 6.7%. On multivariate analyses, HCV-Ab positivity (hazard ratio (HR), 1.93; P=0.02) and pre-transplant liver dysfunction (HR, 1.85; P<0.01), as well as advanced HCT risk, unrelated donors, HLA mismatch and cyclosporine as GvHD prophylaxis, were significant risk factors for hepatic aGvHD, whereas hepatitis B virus surface Ag was not. Hepatic aGvHD was a significant risk factor for low overall survival and high transplant-related mortality in all aGvHD grades (P<0.01). This study is the first to show the relationship between pre-transplant liver conditions and hepatic aGvHD. A prospective study is awaited to validate the results of this study and establish a new strategy especially for high-risk patients.

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We would like to thank all the physicians and data managers at the centers who contributed valuable data on transplantation to the Japan Society for Hematopoietic Cell Transplantation (JSHCT), the Japan Marrow Donor Program (JMDP), the Japan Cord Blood Bank Network (JCBBN) and Transplant Registry Unified Management Program. We also thank the members of the Data Management Committees of JSHCT, JMDP, JCBBN and Transplant Registry Unified Management Program for their assistance. We also thank Dr Fumiaki Nakamura in the University of Tokyo for his critical advice for statistical analyses. This study was supported by research funding from the Ministry of Education, Science, Sports and Culture in Japan to TK.

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Correspondence to T Kondo.

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Arai, Y., Kanda, J., Nakasone, H. et al. Risk factors and prognosis of hepatic acute GvHD after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 51, 96–102 (2016).

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