Meguro Makoto, Mizuguchi Toru, Nishidate Toshihiko, Okita Kenji, Ishii Masayuki, Ota Shigenori, Ueki Tomomi, Akizuki Emi, Hirata Koichi
Makoto Meguro, Toru Mizuguchi, Toshihiko Nishidate, Kenji Okita, Masayuki Ishii, Shigenori Ota, Tomomi Ueki, Emi Akizuki, Koichi Hirata, Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan.
World J Gastroenterol. 2015 Apr 28;21(16):4933-45. doi: 10.3748/wjg.v21.i16.4933.
To clarify the utility of using des-γ-carboxy prothrombin (DCP) and α-fetoprotein (AFP) levels to predict the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) and the hepatitis C virus (HCV) infections.
A total of 205 patients with HCC (105 patients with HBV infection 100 patients with HCV infection) who underwent primary hepatectomy between January 2004 and May 2012 were enrolled retrospectively. Preoperative AFP and DCP levels were used to create interactive dot diagrams to predict recurrence within 2 years after hepatectomy, and cutoff levels were calculated. Patients in the HBV and HCV groups were classified into three groups: a group with low AFP and DCP levels (LL group), a group in which one of the two parameters was high and the other was low (HL group), and a group with high AFP and DCP levels (HH group). Liver function parameters, the postoperative recurrence-free survival rate, and postoperative overall survival were compared between groups. The survival curves were compared by log-rank test using the Kaplan-Meier method. Multivariate analysis using a Cox forward stepwise logistic regression model was conducted for a prognosis.
The preoperative AFP cutoff levels for recurrence within 2 years after hepatectomy in the HBV and HCV groups were 529.8 ng/mL and 60 mAU/mL, respectively; for preoperative DCP levels, the cutoff levels were 21.0 ng/mL in the HBV group and 67 mAU/mL in the HCV group. The HBV group was significantly different from the other groups in terms of vascular invasion, major hepatectomy, volume of intraoperative blood loss, and surgical duration. Significant differences were found between the LL group, the HL group, and the HH group in terms of both mean disease-free survival time (MDFST) and mean overall survival time (MOST): 64.81 ± 7.47 vs 36.63 ± 7.62 vs 18.98 ± 6.17 mo (P = 0.001) and 85.30 ± 6.55 vs 59.44 ± 7.87 vs 46.57 ± 11.20 mo (P = 0.018). In contrast, the HCV group exhibited a significant difference in tumor size, vascular invasion, volume of intraoperative blood loss, and surgical duration; however, no significant difference was observed between the three groups in liver function parameters except for albumin levels. In the LL group, the HL group, and the HH group, the MDFST was 50.09 ± 5.90, 31.01 ± 7.21, and 14.81 ± 3.08 mo (log-rank test, P < 0.001), respectively, and the MOST was 79.45 ± 8.30, 58.82 ± 7.56, and 32.87 ± 6.31 mo (log-rank test, P < 0.001), respectively.
In the HBV group, the prognosis was poor when either AFP or DCP levels were high. In the HCV group, the prognosis was good when either or both levels were low; however, the prognosis was poor when both levels were high. High levels of both AFP and DCP were an independent risk factor associated with tumor recurrence in the HBV and HCV groups. The relationship between tumor marker levels and prognosis was characteristic to the type of viral hepatitis.
阐明使用去γ-羧基凝血酶原(DCP)和甲胎蛋白(AFP)水平预测乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)感染患者肝细胞癌(HCC)预后的效用。
回顾性纳入2004年1月至2012年5月间接受原发性肝切除术的205例HCC患者(105例HBV感染患者和100例HCV感染患者)。术前AFP和DCP水平用于绘制交互式点图,以预测肝切除术后2年内的复发情况,并计算临界值。HBV组和HCV组患者分为三组:AFP和DCP水平均低的组(LL组)、两个参数之一高而另一个低的组(HL组)、AFP和DCP水平均高的组(HH组)。比较各组间的肝功能参数、术后无复发生存率和术后总生存期。采用Kaplan-Meier法通过对数秩检验比较生存曲线。使用Cox向前逐步逻辑回归模型进行多因素分析以评估预后。
HBV组和HCV组肝切除术后2年内复发的术前AFP临界值分别为529.8 ng/mL和60 mAU/mL;术前DCP水平方面,HBV组临界值为21.0 ng/mL,HCV组为67 mAU/mL。HBV组在血管侵犯、肝大部切除术、术中失血量和手术时长方面与其他组有显著差异。LL组、HL组和HH组在平均无病生存期(MDFST)和平均总生存期(MOST)方面均存在显著差异:64.81±7.47 vs 36.63±7.62 vs 18.98±6.17个月(P = 0.001)以及85.30±6.55 vs 59.44±7.87 vs 46.57±11.20个月(P = 0.018)。相比之下,HCV组在肿瘤大小、血管侵犯、术中失血量和手术时长方面有显著差异;然而,除白蛋白水平外,三组间肝功能参数无显著差异。在LL组、HL组和HH组中,MDFST分别为50.09±5.90、31.01±7.21和14.81±3.08个月(对数秩检验,P<0.001),MOST分别为79.45±8.30、58.82±7.56和32.87±6.31个月(对数秩检验,P<0.001)。
在HBV组中,AFP或DCP水平高时预后较差。在HCV组中,AFP或DCP水平低时预后良好;然而,两者水平均高时预后较差。AFP和DCP水平高是HBV组和HCV组中与肿瘤复发相关的独立危险因素。肿瘤标志物水平与预后的关系因病毒性肝炎类型而异。