Yang Fan, Ma Longteng, Yang Yuan, Liu Wenbin, Zhao Jun, Chen Xi, Wang Mengchao, Zhang Hongwei, Cheng Shuqun, Shen Feng, Wang Hongyang, Zhou Weiping, Cao Guangwen
Department of Epidemiology, Second Military Medical University, Shanghai, China.
Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Front Oncol. 2019 May 21;9:370. doi: 10.3389/fonc.2019.00370. eCollection 2019.
The contribution of hepatitis B virus (HBV) infection to the aggressiveness of primary liver cancer (PLC) remains controversial. We aimed to characterize this in eastern China. We enrolled 8,515 PLC patients whose specimens were reserved at the BioBank of the hepatobiliary hospital (Shanghai, China) during 2007-2016. Of those, 3,124 who received primary radical resection were involved in survival analysis. A nomogram was constructed to predict the survivals using preoperative parameters. Hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular cholangiocarcinoma (CHC) accounted for 94.6, 3.7, and 1.7%, respectively. The rates of HBV infection were 87.5, 49.2, and 80.6%, respectively. HBV infection was significantly associated with 10-year earlier onset, more cirrhosis, higher α-fetoprotein, higher carbohydrate antigen 19-9 (CA19-9), more microvascular invasion (MVI), lower neutrophil-to-lymphocyte ratio (NLR), and lower platelet-to-lymphocyte ratio (PLR) in HCC. HBV infection was also associated with 7-year earlier onset, more cirrhosis, higher α-fetoprotein, more MVI, and lower PLR in ICC. In the multivariate Cox analysis, high circulating HBV DNA, α-fetoprotein, CA19-9, NLR, tumor size, number, encapsulation, Barcelona Clinic Liver Cancer (BCLC) stage, and MVI predicted an unfavorable prognosis in HCC; only CA19-9 and BCLC stage, rather than HBV-related parameters, had prognostic values in ICC. A nomogram constructed with preoperative HBV-related parameters including HBV load, ultrasonic cirrhosis, and α-fetoprotein perform better than the current staging systems in predicting postoperative survival in HCC. HBV promotes the aggressiveness of HCC in Chinese population. The contributions of HBV to ICC and other etiological factors to HCC might be indirect arousing non-resolving inflammation.
乙型肝炎病毒(HBV)感染对原发性肝癌(PLC)侵袭性的影响仍存在争议。我们旨在对中国东部地区的这种情况进行特征描述。我们纳入了2007年至2016年期间在肝胆医院(中国上海)生物样本库中留存标本的8515例PLC患者。其中,3124例接受了原发性根治性切除术的患者参与了生存分析。构建了一个列线图,使用术前参数预测生存率。肝细胞癌(HCC)、肝内胆管癌(ICC)和肝内胆管肝细胞癌(CHC)分别占94.6%、3.7%和1.7%。HBV感染率分别为87.5%、49.2%和80.6%。HBV感染与HCC患者发病早10年、更多肝硬化、更高甲胎蛋白、更高糖类抗原19-9(CA19-9)、更多微血管侵犯(MVI)、更低中性粒细胞与淋巴细胞比值(NLR)以及更低血小板与淋巴细胞比值(PLR)显著相关。HBV感染还与ICC患者发病早7年、更多肝硬化、更高甲胎蛋白、更多MVI以及更低PLR相关。在多因素Cox分析中,高循环HBV DNA、甲胎蛋白、CA19-9、NLR、肿瘤大小、数量、包膜、巴塞罗那临床肝癌(BCLC)分期和MVI预测HCC患者预后不良;在ICC中,只有CA19-9和BCLC分期具有预后价值,而非HBV相关参数。用包括HBV载量、超声肝硬化和甲胎蛋白等术前HBV相关参数构建的列线图在预测HCC术后生存方面比当前分期系统表现更好。HBV促进了中国人群中HCC的侵袭性。HBV对ICC的影响以及其他HCC病因学因素的影响可能是间接的,引发了持续性炎症。