title: Higher Bilirubin Levels of Healthy Living Liver Donors Are Associated With Lower Posttransplant Hepatocellular Carcinoma Recurrence.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: 1 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, Korea.
authors.forename: Sangbin
authors.initials: S
authors.lastname: Han
authors.forename: Ju Dong
authors.initials: JD
authors.lastname: Yang
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Sinn
authors.forename: Justin Sangwook
authors.initials: JS
authors.lastname: Ko
authors.forename: Jong Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Jun Chul
authors.initials: JC
authors.lastname: Shin
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Son
authors.forename: Mi Sook
authors.initials: MS
authors.lastname: Gwak
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Joh
authors.forename: Gaab Soo
authors.initials: GS
authors.lastname: Kim
mesh_terms: D000328:Adult; D001663:Bilirubin / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D002454:Cell Differentiation; D046148:Donor Selection; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects* / Q000401:mortality; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D065840:Protective Factors; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: C097353:AFP protein, human; D015415:Biomarkers; D000509:alpha-Fetoproteins; D001663:Bilirubin