血小板计数和平均血小板体积与肝硬化及不可切除肝细胞癌患者总生存期的相关性
Association of Platelet Count and Mean Platelet Volume with Overall Survival in Patients with Cirrhosis and Unresectable Hepatocellular Carcinoma.
作者信息
Scheiner Bernhard, Kirstein Martha, Popp Sabine, Hucke Florian, Bota Simona, Rohr-Udilova Nataliya, Reiberger Thomas, Müller Christian, Trauner Michael, Peck-Radosavljevic Markus, Vogel Arndt, Sieghart Wolfgang, Pinter Matthias
机构信息
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria.
出版信息
Liver Cancer. 2019 May;8(3):203-217. doi: 10.1159/000489833. Epub 2018 Jun 22.
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 < 0.001), less macrovascular invasion (21.2 vs. 31.0%, = 0.005), and lower BCLC stages (63.0 vs. 73.4% BCLC C/D; = 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; = 0.001; MPV ≥11 fL: 11.7 [9.1-14.2] vs. 6.0 [4.4-7.6] months; < 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]; = 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; < 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.
背景
据报道，血小板会影响肿瘤生物学特性并可能促进转移。传统上，血小板减少作为肝硬化的一个标志，与肝细胞癌（HCC）的发生有关。然而，血小板计数对已确诊HCC患者预后的影响尚未得到充分研究。
方法
对1995年至2013年（推导队列）以及2000年至2016年（验证队列）期间诊断为HCC的肝硬化患者进行回顾性研究，这些患者不符合手术治疗条件且未接受抗血小板治疗。血小板减少定义为血小板计数<150 g/L。高平均血小板体积（MPV）定义为≥各队列的中位数（推导队列：≥11 fL；验证队列：≥10.6 fL）。
结果
在626例不可切除HCC患者中，378例（60.4%）存在血小板减少，且与较好的基线肿瘤特征相关：最大结节直径较小（5.6±3.2 vs. 7.6±4.2 cm）、肝外转移较少（9.5% vs. 20.2%，均<0.001）、大血管侵犯较少（21.2% vs. 31.0%，P = 0.005）以及BCLC分期较低（BCLC C/D期为63.0% vs. 73.4%；P = 0.007），与血小板计数正常的患者相比。单因素分析显示，血小板减少和较大的MPV与较长的总生存期（OS）相关（血小板减少：中位OS[95%CI]，11.5[9.3 - 13.8]个月 vs. 5.5[3.8 - 7.1]个月；P = 0.001；MPV≥11 fL：11.7[9.1 - 14.2]个月 vs. 6.0[4.4 - 7.6]个月；P<0.001）。多因素分析中，血小板减少和较大MPV的联合变量与较长的OS独立相关（HR[95%CI]，0.80[0.65 - 0.98]；P = 0.029）。这些结果在一个由525例肝硬化和HCC患者组成的独立外部验证队列中得到证实。同样，血小板减少和高MPV的患者OS明显更长（15.3[11.7 - 18.9]个月 vs. 9.3[7.4 - 11.2]个月；P<0.001）。
结论
血小板减少和较高的MPV与晚期HCC患者较好的预后相关。这些发现可能促使在HCC的预防和管理中对附加抗血小板治疗进行进一步的临床研究。
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