Excessive intraoperative blood loss independently predicts recurrence of hepatocellular carcinoma after liver transplantation

Abstract

Background: Several studies have investigated the effect of intraoperative blood loss (IBL) on recurrence of tumors. However, the independent effect of IBL on oncological outcome after liver transplantation (LT) for hepatocellular carcinoma (HCC) is unclear.

Methods: A total of 479 patients who underwent LT for HCC from January 2001 to December 2012 at our institution were enrolled in this retrospective study. Kaplan-Meier and Cox regression methods were used to assess the recurrence rate, as well as its risk factors. Stratified analysis was performed to further examine the effect of IBL on HCC recurrence according to different characteristics of tumors. We also investigated the independent risk factors for excessive IBL using logistic regression analysis.

Results: The median follow-up was 28 months (range, 1-131 months). Kaplan-Meier analysis with the log-rank test according to IBL at per liter intervals showed that IBL > 4 L was significantly associated with a higher recurrence rate (P < 0.001). Multivariate analysis identified that IBL > 4 L (P < 0.001; hazard ratio [HR] = 2.32, 95 % confidence interval [CI] = 1.60-3.36) was an independent risk factor for post-LT HCC recurrence, as well as age < 60 years, exceeding Milan criteria, α-fetoprotein levels > 400 ng/mL, and micro- and macrovascular invasion. IBL > 4 L (P < 0.001; HR = 2.45, 95 % CI = 1.64-3.66) was also independently associated with early (within 1 year) recurrence after LT. Furthermore, a significant correlation between IBL > 4 L and vascular invasion (P = 0.019) was found. IBL > 4 L was independently associated with HCC recurrence for patients with vascular invasion, but not for patients without vascular invasion. Finally, we found that the presence of ascites, model for end-stage liver disease score, and operation time were independent risk factors for IBL > 4 L.

Conclusions: Excessive IBL is an independent predictor of HCC recurrence after LT, especially in patients with vascular invasion.

Fig. 1

Kaplan–Meier curves for cumulative recurrence rates after liver transplantation for the entire patient cohort. The 1-, 3-, and 5-year recurrence-free survival rates were 33.3 %, 44.4 %, and 46.2 %, respectively

Fig. 2

Kaplan–Meier curves for cumulative recurrence rates according to IBL. One- and 3-year recurrence rates were 30.5 % and 42.0 % for IBL ≤ 4 L, and 52.6 and 62.8 % for IBL > 4 L, respectively

Fig. 3

Kaplan–Meier curves for cumulative recurrence rates classified according to IBL and vascular invasion status. IBL > 4 L was not significantly associated with HCC recurrence in patients without vascular invasion (a). However, in patients with vascular invasion, IBL > 4 L predicted a significantly higher recurrence rate (b)