健康活体肝供体较高的胆红素水平与肝移植后肝细胞癌复发率较低相关。

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

作者信息

Han Sangbin, Yang Ju Dong, Sinn Dong Hyun, Ko Justin Sangwook, Kim Jong Man, Shin Jun Chul, Son Hee Jeong, Gwak Mi Sook, Joh Jae-Won, Kim Gaab Soo

机构信息

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.

出版信息

Transplantation. 2016 Sep;100(9):1933-8. doi: 10.1097/TP.0000000000001293.

DOI:10.1097/TP.0000000000001293

PMID:27362316

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.

摘要

背景

血清胆红素水平可能反映机体对氧化应激增加的防御能力，与癌症发生风险呈负相关。在肝移植中，供体肝脏固有的胆红素代谢随后会转移至受体。因此，我们推测，由血清胆红素水平较高的活体供体进行肝移植可降低肝细胞癌（HCC）复发风险。

方法

本研究纳入了250例符合米兰标准、因治疗HCC而接受肝移植的受体。采用Fine和Gray回归模型分析供体术前总胆红素浓度与HCC复发风险之间的关联，将移植后死亡作为竞争风险事件，并对包括甲胎蛋白、组织学分化和微血管侵犯在内的肿瘤生物学因素进行校正。

结果

所有供体均确认无潜在肝胆疾病或血液系统疾病。供体术前总胆红素浓度中位数为0.7mg/dL，范围为0.2至2.7mg/dL。35例（14.0%）受体发生HCC复发。多变量分析显示，供体术前总胆红素浓度与复发风险呈负相关（风险比，0.22；95%置信区间，0.07 - 0.72；P = 0.013）。供体术前总胆红素最高三分位数（≥1.0mg/dL）与最低三分位数（≤0.6mg/dL）相比，复发风险显著降低（风险比，0.28；95%置信区间，0.11 - 0.70；P = 0.006）。