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Higher Bilirubin Levels of Healthy Living Liver Donors Are Associated With Lower Posttransplant Hepatocellular Carcinoma Recurrence

Sangbin Han1 Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 2 Department of Anesthesiology and Pain Medicine, Kangwon National University School of Medicine, Chuncheon, Korea. 3 Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN. 4 Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 5 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaJu Dong YangEthic committee of the Samsung Medical Center, identifier 2013-12-120Dong Hyun SinnEthic committee of the Samsung Medical Center, identifier 2013-12-120Justin Sangwook KoEthic committee of the Samsung Medical Center, identifier 2013-12-120Jong Man KimEthic committee of the Samsung Medical Center, identifier 2013-12-120Jun Chul ShinEthic committee of the Samsung Medical Center, identifier 2013-12-120Hee Jeong SonEthic committee of the Samsung Medical Center, identifier 2013-12-120Mi Sook GwakEthic committee of the Samsung Medical Center, identifier 2013-12-120Jae‐Won JohEthic committee of the Samsung Medical Center, identifier 2013-12-120Gaab Soo KimSupplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com)
Transplantationjournal2016en
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BACKGROUND: Serum bilirubin level, which may reflect the host defense against increased oxidative stress, is inversely associated with the risk of cancer development. In liver transplantation, the intrinsic bilirubin metabolism of donor liver is subsequently translated into recipient. Thus, we hypothesized that liver transplantation conducted with living donors with higher serum bilirubin reduces hepatocellular carcinoma (HCC) recurrence. METHODS: Two hundred fifty recipients who underwent liver transplantation for treating HCC within the Milan criteria were included in the study. The association between donor preoperative total bilirubin concentration and the risk of HCC recurrence was analyzed using the Fine and Gray regression model with posttransplant death as a competing risk event with adjustment for tumor biology including α-fetoprotein, histological differentiation, and microvascular invasion. RESULTS: All donors were confirmed to have no underlying hepatobiliary diseases or hematological disorders. Donor preoperative total bilirubin concentration was 0.7 mg/dL in median and ranged from 0.2 to 2.7 mg/dL. Thirty-five (14.0%) recipients developed HCC recurrence. Multivariable analysis demonstrated that donor preoperative total bilirubin concentration was inversely associated with the recurrence risk (hazard ratio, 0.22; 95% confidence interval, 0.07-0.72; P = 0.013). The highest (≥1.0 mg/dL) versus lowest (≤0.6 mg/dL) tertile of donor preoperative total bilirubin showed a significant reduction of the recurrence risk (hazard ratio, 0.28; 95% confidence interval, 0.11-0.70; P = 0.006). CONCLUSIONS: Hepatocellular carcinoma recurrence risk decreases in relation to the increase in total serum bilirubin level of healthy living donors without underlying hepatobiliary or hematological disorders. Further validation of bilirubin as a potent anticancer substance against HCC is warranted.

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