Toyoda Hidenori, Kumada Takashi, Tada Toshifumi, Yama Tsuyoki, Mizuno Kazuyuki, Sone Yasuhiro, Maeda Atsuyuki, Kaneoka Yuji, Akita Tomoyuki, Tanaka Junko
Department ofGastroenterology, Ogaki Municipal Hospital, Ogaki, Japan.
Department ofRadiology, Ogaki Municipal Hospital, Ogaki, Japan.
Cancer Sci. 2017 Dec;108(12):2438-2444. doi: 10.1111/cas.13406. Epub 2017 Oct 20.
The aim of the present study was to evaluate the prognostic significance of serum markers that reflect tumor progression, liver function, or liver fibrosis in patients with hepatocellular carcinoma (HCC), focusing on how their impact changes over time after diagnosis. Alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), albumin-bilirubin (ALBI) score, aspartate aminotransferase to platelet ratio index (APRI), and FIB-4 index were measured at the time of initial non-recurrent HCC diagnosis in 1669 patients between 1997 and 2016. Survival rates after diagnosis were compared after stratifying patients by these markers. Time-dependent receiver-operating characteristics (ROC) analysis was carried out to assess how these markers predict patient survival or death. Serum AFP and DCP levels, ALBI score, and APRI and FIB-4 index were strongly correlated with HCC progression, liver function, and degree of liver fibrosis, respectively. Survival rates after diagnosis were significantly different when patients were stratified by these markers. In the time-dependent ROC analysis, AFP and DCP had a high prognostic impact within 3 years of diagnosis but the impact decreased thereafter. In contrast, APRI and FIB-4 index had higher prognostic impact 10 years after diagnosis. ALBI score had a high prognostic impact throughout the study period. Time-dependent ROC analysis clearly showed changes in the prognostic importance of serum markers based on the duration after diagnosis. Whereas the prognostic impact of tumor progression markers was strong in the short term, liver fibrosis markers had higher prognostic impact long after diagnosis. Liver function had constant prognostic impact on patient survival after diagnosis.
本研究的目的是评估反映肿瘤进展、肝功能或肝纤维化的血清标志物在肝细胞癌（HCC）患者中的预后意义，重点关注诊断后其影响如何随时间变化。在1997年至2016年间对1669例初诊为非复发性HCC的患者测定了甲胎蛋白（AFP）、异常凝血酶原（DCP）、白蛋白-胆红素（ALBI）评分、天冬氨酸转氨酶与血小板比值指数（APRI）以及FIB-4指数。根据这些标志物对患者进行分层后，比较诊断后的生存率。进行时间依赖性受试者工作特征（ROC）分析，以评估这些标志物如何预测患者的生存或死亡。血清AFP和DCP水平、ALBI评分以及APRI和FIB-4指数分别与HCC进展、肝功能和肝纤维化程度密切相关。根据这些标志物对患者进行分层时，诊断后的生存率有显著差异。在时间依赖性ROC分析中，AFP和DCP在诊断后3年内具有较高的预后影响，但此后影响降低。相反，APRI和FIB-4指数在诊断后10年具有较高的预后影响。ALBI评分在整个研究期间都具有较高的预后影响。时间依赖性ROC分析清楚地显示了血清标志物的预后重要性随诊断后时间的变化。肿瘤进展标志物的预后影响在短期内较强，而肝纤维化标志物在诊断后很长时间具有较高的预后影响。肝功能对诊断后患者生存具有持续的预后影响。
