Tada Toshifumi, Kumada Takashi, Toyoda Hidenori, Kiriyama Seiki, Tanikawa Makoto, Hisanaga Yasuhiro, Kanamori Akira, Kitabatake Shusuke, Yama Tsuyoki, Tanaka Junko
Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.
Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
Hepatol Res. 2017 Sep;47(10):1021-1031. doi: 10.1111/hepr.12839. Epub 2016 Dec 19.
The rate of hepatocellular carcinoma (HCC) development is reportedly lower in patients with chronic hepatitis C virus (HCV) who have achieved a sustained virological response (SVR) than in patients who were unresponsive to therapy. However, the development of HCC is sometimes observed in patients with SVR. Therefore, we clarified the predictive power of clinical factors for HCC incidence in patients with SVR using receiver operating characteristic (ROC) curve analysis that takes time dependence into account.
A total of 571 patients with HCV who achieved SVR with interferon-based therapy were enrolled. Univariate and multivariate Cox proportional hazards models and time-dependent ROC curves were used to analyze clinical factors associated with the development of HCC.
Twenty-four patients developed HCC during the follow-up period (median duration, 9.0 years). The 5-, 10-, 15-, and 20-year cumulative incidence rates for HCC were 1.7%, 4.8%, 5.8%, and 6.6%, respectively. Multivariate Cox proportional hazards models showed that older age (hazard ratio [HR], 3.648), male sex (HR, 7.560), lower platelet count at 24 weeks after the end of treatment (SVR24) (HR, 3.939), and higher α-fetoprotein (AFP) at SVR24 (HR, 3.630) were independently associated with HCC development. In addition, time-dependent ROC analysis showed that, compared to platelet count at SVR24, AFP at SVR24 had higher predictive power for HCC incidence approximately 7 years after SVR.
Elevated AFP at SVR24 is a risk factor for HCC in patients with HCV, even those who achieve SVR. α-Fetoprotein is a good predictor of HCC development.
据报道，获得持续病毒学应答（SVR）的慢性丙型肝炎病毒（HCV）患者肝细胞癌（HCC）的发生率低于治疗无应答患者。然而，有时在获得SVR的患者中也会观察到HCC的发生。因此，我们使用考虑时间依赖性的受试者工作特征（ROC）曲线分析，阐明了临床因素对获得SVR患者HCC发生率的预测能力。
共纳入571例接受基于干扰素治疗并获得SVR的HCV患者。采用单因素和多因素Cox比例风险模型以及时间依赖性ROC曲线分析与HCC发生相关的临床因素。
24例患者在随访期间发生HCC（中位随访时间为9.0年）。HCC的5年、10年、15年和20年累积发生率分别为1.7%、4.8%、5.8%和6.6%。多因素Cox比例风险模型显示，年龄较大（风险比[HR]，3.648）、男性（HR，7.560）、治疗结束后24周（SVR24）血小板计数较低（HR，3.939）以及SVR24时甲胎蛋白（AFP）水平较高（HR，3.630）与HCC发生独立相关。此外，时间依赖性ROC分析显示，与SVR24时的血小板计数相比，SVR24时的AFP对SVR后约7年HCC发生率具有更高的预测能力。
SVR24时AFP升高是HCV患者发生HCC的危险因素，即使是那些获得SVR的患者。甲胎蛋白是HCC发生的良好预测指标。
