Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung; Department of Medicine, Chung Shan Medical University, Taichung.
Big Data Research Center, School of Medicine, Fu-Jen Catholic University, New Taipei; Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei; Graduate Institute of Clinical Medicine, China Medical University, Taichung; Division of Gastroenterology and Hepatology, E-Da Hospital, Kaohsiung.
Clin Gastroenterol Hepatol. 2018 Jun;16(6):947-954.e4. doi: 10.1016/j.cgh.2017.09.031. Epub 2017 Sep 22.
BACKGROUND & AIMS: Chronic infection with hepatitis B virus (HBV) increases risk of intrahepatic cholangiocarcinoma (ICC), but it is not clear whether antiviral therapy reduces risk. We investigated the association between nucleos(t)ide analogue therapy and ICC risk.
We performed a nationwide long-term cohort study using Taiwan's National Health Insurance Research Database to obtain data on 185,843 patients with chronic HBV infection from October 1, 2003 through December 31, 2012. We excluded patients with confounding disorders such as infection with hepatitis C virus, HIV, or other hepatitis-associated viruses; liver flukes; biliary stone diseases; cholangitis; congenital biliary anomalies; biliary tract surgeries; or cancer. We identified 10,062 patients who received nucleos(t)ide analogue therapy (the treated group), and used propensity scores to match them (1:1) with patients who received hepatoprotectants (the untreated group). Cumulative incidences of and hazard ratios (HRs) for ICC development were analyzed.
The cumulative incidence of ICC was significantly lower in the treated group after 3 years of therapy (1.28%; 95% CI, 0.56-2.01) than in the untreated group (3.14%; 95% CI, 2.02-4.27) and after 5 years of therapy (1.53%; 95% CI, 0.73-2.33 vs 4.32% in untreated group; 95% CI, 2.96-5.6869). In multivariable regression analysis, nucleos(t)ide analogue therapy was independently associated with a reduced risk of ICC (HR, 0.44; 95% CI, 0.25-0.78; P = .005). Older age (HR 1.05 per year; 95% CI, 1.03-1.07) and cirrhosis (HR, 2.80; 95% CI, 1.52-5.1415) were independently associated with an increased risk of ICC. Sensitivity analyses verified the association between nucleos(t)ide analogue therapy and a reduced ICC risk.
A nationwide long-term cohort study in Taiwan showed that nucleos(t)ide analogue therapy for chronic HBV infection is significantly associated with a reduced ICC risk.
乙型肝炎病毒（HBV）慢性感染会增加肝内胆管癌（ICC）的风险，但抗病毒治疗是否能降低风险尚不清楚。我们研究了核苷（酸）类似物治疗与 ICC 风险之间的关系。
我们使用台湾全民健康保险研究数据库进行了一项全国性的长期队列研究，从 2003 年 10 月 1 日至 2012 年 12 月 31 日获得了 185843 例慢性 HBV 感染患者的数据。我们排除了伴有丙型肝炎病毒、HIV 或其他肝炎相关病毒感染、肝吸虫、胆石病、胆管炎、先天性胆管异常、胆道手术或癌症等混杂疾病的患者。我们确定了 10062 例接受核苷（酸）类似物治疗的患者（治疗组），并使用倾向评分对他们进行了 1：1 匹配（未治疗组），匹配的因素为接受保肝药物治疗的患者。分析 ICC 发展的累积发生率和风险比（HRs）。
治疗 3 年后，治疗组 ICC 的累积发生率明显低于未治疗组（1.28%；95%CI，0.56-2.01），治疗 5 年后（1.53%；95%CI，0.73-2.33 vs 未治疗组 4.32%；95%CI，2.96-5.6869）也明显低于未治疗组。多变量回归分析显示，核苷（酸）类似物治疗与 ICC 风险降低独立相关（HR，0.44；95%CI，0.25-0.78；P=0.005）。年龄较大（每年 HR 增加 1.05；95%CI，1.03-1.07）和肝硬化（HR，2.80；95%CI，1.52-5.1415）与 ICC 风险增加独立相关。敏感性分析证实了核苷（酸）类似物治疗与 ICC 风险降低之间的关联。
台湾一项全国性的长期队列研究表明，慢性 HBV 感染的核苷（酸）类似物治疗与 ICC 风险降低显著相关。
