Association of platelet count and mean platelet volume with overall survival in patients with cirrhosis and unresectable hepatocellular carcinoma

Background:

Platelets have been reported to influence tumor biology and may promote metastasis. Traditionally, thrombocytopenia – a hallmark of cirrhosis – was associated with hepatocellular carcinoma (HCC) development. However, the impact of platelet count on outcome in patients with HCC is not well studied.

Methods:

Outcomes of cirrhotic patients with diagnosis of HCC between 1995 – 2013 (derivation cohort) and 2000 – 2016 (validation cohort) who were not eligible for surgical treatment and did not receive anti-platelet therapy were retrospectively studied. Results were validated in an independent cohort provided by Hannover Medical School. Thrombocytopenia was defined as a platelet count < 150G/L. High mean platelet volume (MPV) was defined as ≥ median value of the respective cohort (derivation cohort: ≥11fL; validation cohort: ≥10.6fL).

Results:

Among 626 patients with unresectable HCC, thrombocytopenia was present in 378 (60.4%) and was associated with favourable baseline tumor characteristics: lower diameter of the largest nodule (5.6 ± 3.2 vs. 7.6 ± 4.2 cm), less extrahepatic spread (9.5% vs. 20.2%, both p < 0.001), less macrovascular invasion (21.2% vs. 31.0%, p = 0.005), lower BCLC stages (63.0% vs. 73.4% BCLC C/D; p = 0.007) as compared to patients with normal platelet count. On univariate analysis, thrombocytopenia and larger MPV were associated with longer overall survival (OS) (thrombocytopenia: median OS (95%CI), 11.5 (9.3 – 13.8) vs. 5.5 (3.8 – 7.1) months; p = 0.001; MPV ≥11fL: 11.7 (9.1 – 14.2) vs. 6.0 (4.4 – 7.6) months; p < 0.001). In multivariate analysis, the combined variable of thrombocytopenia and larger MPV was independently associated with longer OS (HR (95%CI), 0.79 (0.64 – 0.97); p = 0.026). These results were confirmed in a validation cohort of 806 patients with cirrhosis and HCC. Again, patients with thrombocytopenia and high MPV had significantly longer OS (13.2 (10.8 – 15.5) vs. 8.3 (7.2 – 9.4)).

Conclusions:

Thrombocytopenia and higher mean platelet volume are associated with better outcome in patients with advanced HCC. These findings may prompt further research on additive anti-platelet therapy in the management of HCC.