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High preop platelet count increases HCC recurrence risk after liver transplantation

The risk for hepatocellular carcinoma recurrence after living donor liver transplantation increased in correlation with higher preoperative platelet count, according to a recently published study.

“The relationship between platelets and tumors is not a simple epiphenomenon resulting from tumor-induced thrombopoiesis, but rather a direct contribution of platelets to multiple steps in the cancer progression, including tumor cell angiogenesis, protection from immune attack, extravasation, and arrest within the vasculature,” Sangbin Han, MD, from the Sungkyunkwan University School of Medicine, South Korea, and colleagues wrote. “This study demonstrated the independent association of preoperative [platelet count (PLT)] with posttransplant HCC recurrence.”

Han and colleagues enrolled 359 patients who underwent first living donor liver transplantation between May 2002 and April 2016 at a single center. The researchers designated patients with a preoperative PLT of 75 x 10⁹/L or less (n = 240) as having a low risk for HCC recurrence and those with a higher count as having a higher risk (n = 119).

Compared with patients in the low risk group, those with a higher preoperative PLT were more likely to have Edmonson grades 3 and 4 (13.4% vs. 6.7%; P = .03), microvascular invasion (47.9% vs. 30.8%; P = .002) and bile duct invasion (6.7% vs. 0.8%; P = .001). Patients in the low risk group were more likely to have cirrhosis (98.3% vs. 86.6%; P < .001) or a MELD score higher than 25 (10.4% vs. 4.2%; P = .045)

At a median follow-up of 59 months, 31 HCC-related deaths occurred and 47 patients died due to other reasons. The risk for HCC-related death was significantly higher among the high preoperative PLT group (HR = 4.98; 95% CI, 2.34-10.62).

After a median follow-up time of 13 months, 60 patients with an average PLT of 138 x 10⁹/L (range, 101-179 x 10⁹/L) experienced HCC recurrence. Continuous preoperative PLT correlated with recurrence risk (HR = 1.01; 95% CI, 1.01-1.02). Multivariate analysis confirmed a significantly higher risk for HCC recurrence in the high preoperative PLT group (HR = 2.1; 95% CI, 1.23-3.6).

To further verify their results, the researchers matched 97 pairs of recipients from the low PLT group (n = 209) and the high PLT group (n = 97). Fifty of those patients experienced HCC recurrence. After both univariate (HR = 2.33; 95% CI, 1.36-4.01) and multivariate analysis (HR = 1.9; 95% CI, 1.02-3.54), the correlation between high preoperative PLT and increased risk for HCC recurrence remained significant.

“It could be deduced that patients with higher preoperative PLTs continue to experience greater platelet-tumor cell interactions and a more favorable microenvironment for metastasis early after transplantation when surgery-induced stress, inflammation, and immunomodulation provide a time window of vulnerability to metastasis,” the researchers concluded. “Taken together, the results from the current study suggest a potentially important role of platelets in HCC metastasis after living donor liver transplantation, which might provide a potential therapeutic target.” – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.