Background:

Currently, there is an increasing body of evidence that risk of early hepatocellular carcinoma (HCC) relapse following liver transplantation (LT) may be promoted by mechanisms related to ischemia-reperfusion injury (IRI). Intraoperative blood loss (IBL) is a trigger of pro-inflammatory and immunosuppressive processes. The aim of this trial was to analyze the impact of IBL on risk of early HCC relapse post-LT.

Methods:

106 liver transplant patients with HCC were analyzed. Pretransplant tumor staging included 18F-FDG positron emission tomography (PET) for assessing biological tumor aggressiveness (PET + versus PET – HCC). IBL was calculated ultimately post-LT. The impact of IBL along with other established clinical and pathologic variables on early (within 12 months) HCC recurrence after LT was assessed in uni- and multivariate analysis.

Results:

Sixty-seven patients demonstrated PET-negative HCC, while 39 patients had 18F-FDG-avid tumors on pretransplant PET. Twenty-five patients were suffering from HCC recurrence (23.6%), 19 within 12 months (82.6%). In univariate analysis, AFP level > 400IU/ml, donor age > 50y, HCC exceeding the Milan criteria, PET-positive tumors, total ischemia time > 450min, IBL > 1500ml, poor tumor grading, lymphovascular invasion and microvascular invasion (MVI) were related to early HCC relapse (P < 0.05). After multivariate analysis, only IBL > 1500ml (Hazard ratio [HR] = 14.8; P < 0.001) and MVI (HR = 13.6, P = 0.002) remained as independent predictors of early post-LT tumor recurrence. Increased IBL correlated with ischemia-reperfusion damage to the graft (aminotransferases) and systemic inflammatory state of the patient (C-reactive protein levels; P < 0.05). In patients with 18F-FDG non-avid HCC, IBL had no impact on outcome. However, in PET-positive HCC, IBL was identified as the only independent promoter of early HCC recurrence (HR = 10.8; P = 0.002). In this special subgroup, 5-year recurrence-free survival rate was 63% in patients with low, but 0% in those with high IBL (P < 0.001).

Conclusion:

Intraoperative blood loss is a strong predictor of early HCC recurrence post-LT, particularly in patients with high risk HCC. Thus, approaches of bleeding minimization could be essential for improving tumor-specific post-LT outcome in advanced HCC.

CITATION INFORMATION: Kornberg A, Witt U, Kornberg J, Friess H, Müller K, Thrum K. Intraoperative Blood Loss Is a Promoter of Early Tumor Recurrence in Liver Transplant Patients with High Risk Hepatocellular Carcinoma. Am J Transplant. 2016;16 (suppl 3).

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