Peripheral blood platelet counts identify prognostically diverse clinical phenotypes in hepatocellular carcinoma.

Background: The factors responsible for hepatocellular carcinoma (HCC) growth are not precisely known.

Aims: To study the clinical parameters associated with increases in maximum tumor diameter (MTD).

Methods: A new cohort of 944 prospectively accrued HCC patients was analyzed for large size associations.

Results: Patients were ordered into MTD terciles. Blood platelets, GGT and AST levels significantly increased and total bilirubin decreased with increase in MTD. Similar results were found only for platelets, in patients with low alpha-fetoprotein (AFP) levels, for whom biomarkers are scanty. Survival significantly decreased for patients with high platelet or GGT levels, even when AFP levels were low.Comparison of patients with low and high platelet levels showed that in the ≤6cm MTD group, patients with higher platelet numbers had lower total bilirubin and AST, and higher albumin, hemoglobin and percent patients with portal vein thrombosis (PVT) than those with lower platelets. Univariable logistic analysis on HCCs >6cm versus ≤6cm revealed significantly higher odds ratios for elevated blood platelet, AFP, GGT and ALKP levels. Cox regression analysis on death showed that in ≤6cm MTD patients, significant hazard ratios were for platelets, GGT, AFP, ALKP and PVT; but not for >6cm MTD patients, suggesting different mechanisms. Given the association of higher platelets with larger tumors and good liver function, their precursors are suggested to be small tumors with higher platelets and endogenous tumor factors. However, patients with low platelets and larger HCCs might have a different HCC lineage, likely associated with liver inflammation factors.

Conclusions: Blood platelet levels are a potential marker for HCC phenotype and prognosis, including in patients with low AFP. They may also be a therapeutic target.