Bernhard Scheiner1,2,3, Martha Kirstein4, Sabine Popp1, Florian Hucke1,2,5, Simona Bota1,2,5, Nataliya Rohr-Udilova1,2, Thomas Reiberger1,3, Christian Müller1,2, Michael Trauner1, Markus Peck-Radosavljevic1,2,5,3, Arndt Vogel4, Wolfgang Sieghart1,2, Matthias Pinter1,2. 1. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. 2. Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria. 3. Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria. 4. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. 5. Department of Gastroenterology and Hepatology, Endocrinology, Rheumatology and Nephrology, Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria.
Abstract
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 established HCC is not well studied. METHODS: Outcomes of patients with cirrhosis diagnosed with HCC between 1995 and 2013 (derivation cohort) and 2000-2016 (validation cohort) who were not eligible for surgical treatment and did not receive antiplatelet therapy were retrospectively studied. Thrombocytopenia was defined as platelet count < 150 g/L. High mean platelet volume (MPV) was defined as ≥median value of the respective cohort (derivation cohort: ≥11 fL; validation cohort: ≥10.6 fL). RESULTS: Among 626 patients with unresectable HCC, thrombocytopenia was present in 378 (60.4%) and was associated with favorable 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), and 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 ≥11 fL: 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], 0.80 [0.65-0.98]; p = 0.029). These results were confirmed in an independent external validation cohort of 525 patients with cirrhosis and HCC. Again, patients with thrombocytopenia and high MPV had significantly longer OS (15.3 [11.7-18.9] vs. 9.3 [7.4-11.2] months; p < 0.001). CONCLUSIONS: Thrombocytopenia and higher MPV are associated with better outcome in patients with advanced HCC. These findings may prompt further clinical research on additive antiplatelet therapy in the prevention and management of HCC.
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 established HCC is not well studied. METHODS: Outcomes of patients with cirrhosis diagnosed with HCC between 1995 and 2013 (derivation cohort) and 2000-2016 (validation cohort) who were not eligible for surgical treatment and did not receive antiplatelet therapy were retrospectively studied. Thrombocytopenia was defined as platelet count < 150 g/L. High mean platelet volume (MPV) was defined as ≥median value of the respective cohort (derivation cohort: ≥11 fL; validation cohort: ≥10.6 fL). RESULTS: Among 626 patients with unresectable HCC, thrombocytopenia was present in 378 (60.4%) and was associated with favorable 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), and 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 ≥11 fL: 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], 0.80 [0.65-0.98]; p = 0.029). These results were confirmed in an independent external validation cohort of 525 patients with cirrhosis and HCC. Again, patients with thrombocytopenia and high MPV had significantly longer OS (15.3 [11.7-18.9] vs. 9.3 [7.4-11.2] months; p < 0.001). CONCLUSIONS: Thrombocytopenia and higher MPV are associated with better outcome in patients with advanced HCC. These findings may prompt further clinical research on additive antiplatelet therapy in the prevention and management of HCC.
Entities:
Keywords:
Cirrhosis; Hepatocellular carcinoma; Mean platelet volume; Survival; Thrombocytopenia
Authors: Matteo Iannacone; Giovanni Sitia; Masanori Isogawa; Patrizia Marchese; Maria G Castro; Pedro R Lowenstein; Francis V Chisari; Zaverio M Ruggeri; Luca G Guidotti Journal: Nat Med Date: 2005-10-30 Impact factor: 53.440
Authors: Anna S Lok; Leonard B Seeff; Timothy R Morgan; Adrian M di Bisceglie; Richard K Sterling; Teresa M Curto; Gregory T Everson; Karen L Lindsay; William M Lee; Herbert L Bonkovsky; Jules L Dienstag; Marc G Ghany; Chihiro Morishima; Zachary D Goodman Journal: Gastroenterology Date: 2008-09-18 Impact factor: 22.682
Authors: Thomas Reiberger; Bernhard Angermayr; Philipp Schwabl; Natascha Rohr-Udilova; Markus Mitterhauser; Alfred Gangl; Markus Peck-Radosavljevic Journal: J Hepatol Date: 2009-08-04 Impact factor: 25.083
Authors: Bernhard Scheiner; Gregor Ulbrich; Mattias Mandorfer; Thomas Reiberger; Christian Müller; Fredrik Waneck; Michael Trauner; Claus Kölblinger; Arnulf Ferlitsch; Wolfgang Sieghart; Markus Peck-Radosavljevic; Matthias Pinter Journal: United European Gastroenterol J Date: 2019-03-21 Impact factor: 4.623