Nam Joon Yeul, Lee Jeong-Hoon, Kim Hwi Young, Kim Jieun E, Lee Dong Hyeon, Chang Young, Cho Hyeki, Yoo Jeong-Ju, Lee Minjong, Cho Young Youn, Cho Yuri, Cho EunJu, Yu Su Jong, Kim Yoon Jun, Yoon Jung-Hwan
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Department of Internal Medicine and Liver Center, Ewha Womans University School of Medicine Seoul, Korea.
PLoS One. 2017 Jan 18;12(1):e0166188. doi: 10.1371/journal.pone.0166188. eCollection 2017.
BACKGROUND/AIMS: Regular surveillance for hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients is essential to detect HCC earlier and to improve prognosis. This study investigated whether prescription of oral medication contributes to adherence to surveillance, early tumor detection, and overall survival (OS).
A total of 401 CHB patients who were newly diagnosed with HCC were included: 134 patients received no medication (group 1), 151 received hepatoprotective agents such as ursodeoxycholic acid and silymarin (group 2), and 116 received antiviral agents (group 3) at two years before HCC diagnosis. The primary endpoint was OS, and secondary endpoints were compliance to regular surveillance and HCC status at diagnosis.
Compared to group 1, both group 2 and 3 had higher rates of good compliance to regular surveillance (defined as participation in >80% of imaging intervals being ≤6 months) (58.2%, 90.1%, and 97.4%, respectively; P<0.001), more HCC diagnosed at a very early stage (20.9%, 32.5%, and 36.2%; P = 0.019) and smaller tumor size (2.8±2.4cm, 1.9±1.1cm, and 1.8±0.9cm; P<0.001). Finally, compared to group 1, both group 2 (hazard ratio, 0.63; 95% confidence interval, 0.41-0.97; P = 0.035) and group 3 (hazard ratio, 0.40; 95% confidence interval, 0.22-0.71; P = 0.002) had significantly longer OS. In mediation analysis, prolonged OS is resulted considerably from indirect effect mediated by shorter imaging interval (>100% in group 2 and 14.5% in group 3) rather than direct effect of medication itself.
Prescription of oral medication improves compliance to surveillance and enables early detection of HCC, which is associated with enhanced survival.
背景/目的：对慢性乙型肝炎（CHB）患者进行肝细胞癌（HCC）的定期监测对于早期发现HCC及改善预后至关重要。本研究调查了口服药物治疗是否有助于提高监测依从性、早期肿瘤检测率及总生存期（OS）。
共纳入401例新诊断为HCC的CHB患者：134例患者未接受药物治疗（第1组），151例在HCC诊断前两年接受了熊去氧胆酸和水飞蓟宾等保肝药物治疗（第2组），116例接受了抗病毒药物治疗（第3组）。主要终点为OS，次要终点为定期监测的依从性及诊断时的HCC状态。
与第1组相比，第2组和第3组定期监测的良好依从率（定义为参与超过80%的成像间隔≤6个月）更高（分别为58.2%、90.1%和97.4%；P<0.001），极早期诊断的HCC更多（分别为20.9%、32.5%和36.2%；P = 0.019），肿瘤大小更小（分别为2.8±2.4cm、1.9±1.1cm和1.8±0.9cm；P<0.001）。最后，与第1组相比，第2组（风险比，0.63；95%置信区间，0.41 - 0.97；P = 0.035）和第3组（风险比，0.40；95%置信区间，0.22 - 0.71；P = 0.002）的OS均显著更长。在中介分析中，OS延长很大程度上是由较短的成像间隔介导的间接效应所致（第2组>100%，第3组14.5%），而非药物本身的直接效应。
口服药物治疗可提高监测依从性并实现HCC的早期检测，这与生存期延长相关。
