Sangbin Han1, Ju Dong Yang2, Dong Hyun Sinn3, Jong Man Kim4, Gyu Sung Choi4, Gangha Jung1, Joong Hyun Ahn5, Seonwoo Kim5, Justin S Ko1, Mi Sook Gwak1, Choon Hyuck D Kwon4, Michael D Leise2, Geum-Youn Gwak3, Julie K Heimbach6, Gaab Soo Kim1. 1. Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 2. Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN. 3. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 4. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 5. Department of Statistics and Data Center, Samsung Medical Center, Seoul, Korea. 6. Division of Transplant Surgery, Mayo Clinic College of Medicine, Rochester, MN.
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.
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.