Risk of Post-transplant Hepatocellular Carcinoma Recurrence Is Higher in Recipients of Livers From Male Than Female Living Donors

Sangbin Han, Ju Dong Yang, Dong Hyun Sinn, Jong Man Kim, Gyu Sung Choi, Gangha Jung, Joong Hyun Ahn, Seonwoo Kim, Justin S. Ko, Mi Sook Gwak, Choon Hyuck D. Kwon, Michael D. Leise, Geum Youn Gwak, Julie K. Heimbach, Gaab Soo Kim

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

OBJECTIVE:: To evaluate the relationship between donor sex and hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation. BACKGROUND:: HCC shows a male predominance in incidence and recurrence after tumor resection due to sex differences in hepatic sex hormone receptors. There have been no studies evaluating the importance of donor sex on post-transplant HCC recurrence. METHODS:: Of 384 recipients of livers, from living donors, for HCC: 104/120 who received grafts from female donors were matched with 246/264 who received grafts from male donors using propensity score matching, with an unfixed matching ratio based on factors like tumor biology. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. RESULTS:: The median follow-up time was 39 months. Before matching, recurrence probability at 1/2/5 years after transplantation was 6.1/9.7/12.7% in recipients with female donors and 11.7/19.2/25.3% in recipients with male donors. Recurrence risk was significantly higher with male donors in univariable analysis (hazard ratio [HR] = 2.04 [1.15–3.60], P = 0.014) and multivariable analysis (HR=2.10 [1.20–3.67], P = 0.018). In the matched analysis, recurrence risk was also higher with male donors (HR=1.92 [1.05–3.52], P = 0.034): both in intrahepatic recurrence (HR=1.92 [1.05–3.51], P = 0.034) and extrahepatic recurrence (HR=1.93 [1.05–3.52], P = 0.033). Multivariable analysis confirmed the significance of donor sex (HR=2.08 [1.11–3.91], P = 0.023). Interestingly, the significance was lost when donor age was >40 years. Two external cohorts validated the significance of donor sex. CONCLUSIONS:: Donor sex appears to be an important graft factor modulating HCC recurrence after living donor liver transplantation.

Original languageEnglish (US)
JournalAnnals of Surgery
DOIs
StateAccepted/In press - Jun 16 2017

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Living Donors
Hepatocellular Carcinoma
Tissue Donors
Transplants
Recurrence
Liver
Liver Transplantation
Propensity Score
Sex Ratio
Gonadal Steroid Hormones
Survival Analysis
Sex Characteristics
Neoplasms
Transplantation

ASJC Scopus subject areas

  • Surgery

Cite this

Risk of Post-transplant Hepatocellular Carcinoma Recurrence Is Higher in Recipients of Livers From Male Than Female Living Donors. / Han, Sangbin; Yang, Ju Dong; Sinn, Dong Hyun; Kim, Jong Man; Choi, Gyu Sung; Jung, Gangha; Ahn, Joong Hyun; Kim, Seonwoo; Ko, Justin S.; Gwak, Mi Sook; Kwon, Choon Hyuck D.; Leise, Michael D.; Gwak, Geum Youn; Heimbach, Julie K.; Kim, Gaab Soo.

In: Annals of Surgery, 16.06.2017.

Research output: Contribution to journalArticle

Han, S, Yang, JD, Sinn, DH, Kim, JM, Choi, GS, Jung, G, Ahn, JH, Kim, S, Ko, JS, Gwak, MS, Kwon, CHD, Leise, MD, Gwak, GY, Heimbach, JK & Kim, GS 2017, 'Risk of Post-transplant Hepatocellular Carcinoma Recurrence Is Higher in Recipients of Livers From Male Than Female Living Donors', Annals of Surgery. https://doi.org/10.1097/SLA.0000000000002318
Han, Sangbin ; Yang, Ju Dong ; Sinn, Dong Hyun ; Kim, Jong Man ; Choi, Gyu Sung ; Jung, Gangha ; Ahn, Joong Hyun ; Kim, Seonwoo ; Ko, Justin S. ; Gwak, Mi Sook ; Kwon, Choon Hyuck D. ; Leise, Michael D. ; Gwak, Geum Youn ; Heimbach, Julie K. ; Kim, Gaab Soo. / Risk of Post-transplant Hepatocellular Carcinoma Recurrence Is Higher in Recipients of Livers From Male Than Female Living Donors. In: Annals of Surgery. 2017.
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title = "Risk of Post-transplant Hepatocellular Carcinoma Recurrence Is Higher in Recipients of Livers From Male Than Female Living Donors",
abstract = "OBJECTIVE:: To evaluate the relationship between donor sex and hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation. BACKGROUND:: HCC shows a male predominance in incidence and recurrence after tumor resection due to sex differences in hepatic sex hormone receptors. There have been no studies evaluating the importance of donor sex on post-transplant HCC recurrence. METHODS:: Of 384 recipients of livers, from living donors, for HCC: 104/120 who received grafts from female donors were matched with 246/264 who received grafts from male donors using propensity score matching, with an unfixed matching ratio based on factors like tumor biology. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. RESULTS:: The median follow-up time was 39 months. Before matching, recurrence probability at 1/2/5 years after transplantation was 6.1/9.7/12.7{\%} in recipients with female donors and 11.7/19.2/25.3{\%} in recipients with male donors. Recurrence risk was significantly higher with male donors in univariable analysis (hazard ratio [HR] = 2.04 [1.15–3.60], P = 0.014) and multivariable analysis (HR=2.10 [1.20–3.67], P = 0.018). In the matched analysis, recurrence risk was also higher with male donors (HR=1.92 [1.05–3.52], P = 0.034): both in intrahepatic recurrence (HR=1.92 [1.05–3.51], P = 0.034) and extrahepatic recurrence (HR=1.93 [1.05–3.52], P = 0.033). Multivariable analysis confirmed the significance of donor sex (HR=2.08 [1.11–3.91], P = 0.023). Interestingly, the significance was lost when donor age was >40 years. Two external cohorts validated the significance of donor sex. CONCLUSIONS:: Donor sex appears to be an important graft factor modulating HCC recurrence after living donor liver transplantation.",
author = "Sangbin Han and Yang, {Ju Dong} and Sinn, {Dong Hyun} and Kim, {Jong Man} and Choi, {Gyu Sung} and Gangha Jung and Ahn, {Joong Hyun} and Seonwoo Kim and Ko, {Justin S.} and Gwak, {Mi Sook} and Kwon, {Choon Hyuck D.} and Leise, {Michael D.} and Gwak, {Geum Youn} and Heimbach, {Julie K.} and Kim, {Gaab Soo}",
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T1 - Risk of Post-transplant Hepatocellular Carcinoma Recurrence Is Higher in Recipients of Livers From Male Than Female Living Donors

AU - Han, Sangbin

AU - Yang, Ju Dong

AU - Sinn, Dong Hyun

AU - Kim, Jong Man

AU - Choi, Gyu Sung

AU - Jung, Gangha

AU - Ahn, Joong Hyun

AU - Kim, Seonwoo

AU - Ko, Justin S.

AU - Gwak, Mi Sook

AU - Kwon, Choon Hyuck D.

AU - Leise, Michael D.

AU - Gwak, Geum Youn

AU - Heimbach, Julie K.

AU - Kim, Gaab Soo

PY - 2017/6/16

Y1 - 2017/6/16

N2 - OBJECTIVE:: To evaluate the relationship between donor sex and hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation. BACKGROUND:: HCC shows a male predominance in incidence and recurrence after tumor resection due to sex differences in hepatic sex hormone receptors. There have been no studies evaluating the importance of donor sex on post-transplant HCC recurrence. METHODS:: Of 384 recipients of livers, from living donors, for HCC: 104/120 who received grafts from female donors were matched with 246/264 who received grafts from male donors using propensity score matching, with an unfixed matching ratio based on factors like tumor biology. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. RESULTS:: The median follow-up time was 39 months. Before matching, recurrence probability at 1/2/5 years after transplantation was 6.1/9.7/12.7% in recipients with female donors and 11.7/19.2/25.3% in recipients with male donors. Recurrence risk was significantly higher with male donors in univariable analysis (hazard ratio [HR] = 2.04 [1.15–3.60], P = 0.014) and multivariable analysis (HR=2.10 [1.20–3.67], P = 0.018). In the matched analysis, recurrence risk was also higher with male donors (HR=1.92 [1.05–3.52], P = 0.034): both in intrahepatic recurrence (HR=1.92 [1.05–3.51], P = 0.034) and extrahepatic recurrence (HR=1.93 [1.05–3.52], P = 0.033). Multivariable analysis confirmed the significance of donor sex (HR=2.08 [1.11–3.91], P = 0.023). Interestingly, the significance was lost when donor age was >40 years. Two external cohorts validated the significance of donor sex. CONCLUSIONS:: Donor sex appears to be an important graft factor modulating HCC recurrence after living donor liver transplantation.

AB - OBJECTIVE:: To evaluate the relationship between donor sex and hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation. BACKGROUND:: HCC shows a male predominance in incidence and recurrence after tumor resection due to sex differences in hepatic sex hormone receptors. There have been no studies evaluating the importance of donor sex on post-transplant HCC recurrence. METHODS:: Of 384 recipients of livers, from living donors, for HCC: 104/120 who received grafts from female donors were matched with 246/264 who received grafts from male donors using propensity score matching, with an unfixed matching ratio based on factors like tumor biology. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. RESULTS:: The median follow-up time was 39 months. Before matching, recurrence probability at 1/2/5 years after transplantation was 6.1/9.7/12.7% in recipients with female donors and 11.7/19.2/25.3% in recipients with male donors. Recurrence risk was significantly higher with male donors in univariable analysis (hazard ratio [HR] = 2.04 [1.15–3.60], P = 0.014) and multivariable analysis (HR=2.10 [1.20–3.67], P = 0.018). In the matched analysis, recurrence risk was also higher with male donors (HR=1.92 [1.05–3.52], P = 0.034): both in intrahepatic recurrence (HR=1.92 [1.05–3.51], P = 0.034) and extrahepatic recurrence (HR=1.93 [1.05–3.52], P = 0.033). Multivariable analysis confirmed the significance of donor sex (HR=2.08 [1.11–3.91], P = 0.023). Interestingly, the significance was lost when donor age was >40 years. Two external cohorts validated the significance of donor sex. CONCLUSIONS:: Donor sex appears to be an important graft factor modulating HCC recurrence after living donor liver transplantation.

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