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

Abstract

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.

• Authors: Sangbin Han, Ju Dong Yang, Dong Hyun Sinn, Justin Sangwook Ko, Jong Man Kim, Jun Chul Shin, Hee Jeong Son, Mi Sook Gwak, Jae-Won Joh, Gaab Soo Kim
• Journal: Transplantation (Transplantation) Vol. 100 Issue 9 Pg. 1933-8 (09 2016) ISSN: 1534-6080 [Electronic] United States
• PMID: 27362316 (Publication Type: Journal Article)

Chemical References

• AFP protein, human
• Biomarkers
• alpha-Fetoproteins
• Bilirubin

Topics

• Adult
• Bilirubin (blood)
• Biomarkers (blood)
• Carcinoma, Hepatocellular (blood, mortality, pathology, surgery)
• Cell Differentiation
• Donor Selection
• Female
• Humans
• Kaplan-Meier Estimate
• Liver Neoplasms (blood, mortality, pathology, surgery)
• Liver Transplantation (adverse effects, mortality)
• Living Donors
• Male
• Middle Aged
• Multivariate Analysis
• Neoplasm Invasiveness
• Neoplasm Recurrence, Local
• Protective Factors
• Retrospective Studies
• Risk Factors
• Time Factors
• Treatment Outcome
• Up-Regulation
• alpha-Fetoproteins (analysis)