Division of Gastroenterology and Hepatology, Stanford University, Stanford, California.
Departments of Medicine and Public Health Sciences, Queen's University, Kingston, Ontario, Canada.
Hepatology. 2018 Oct;68(4):1288-1297. doi: 10.1002/hep.30045.
The risk of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) receiving direct acting antivirals (DAAs) has been debated. This study aims to describe the incidence of HCC among patients listed for liver transplantation (LT) in the DAA era. Individuals with cirrhosis listed for LT from January 2003 to December 2015 were identified using the Scientific Registry for Transplant Recipients database. Patients with HCC at listing or HCC exception within 180 days were excluded. Patients were divided into three eras based on listing date: eras 1 (2003-2010), 2 (2011-2013), and 3 (2014-2015). Incidence rates of HCC were calculated by era and compared using incident rate ratios (IRRs). The association between HCC and listing era was evaluated using Cox regression and competing risk analyses, the latter considering death and LT as competing events. Of the 48,158 eligible wait-list registrants, 3112 (6.5%) received HCC exceptions after a median of 493 days. In 20,039 individuals with HCV, the incidence of HCC was 49% higher in era 3 versus era 1 (IRR 1.49, 95% confidence interval [CI] 1.24-1.79). In multivariate analysis, those in era 3 had a higher hazard of HCC compared with era 1 (hazard ratio 1.22, 95% CI 1.01-1.48). However, in multivariable competing risks analysis, with death and LT considered as competing events for de novo HCC, era was no longer associated with HCC (subdistribution hazard ratio 0.83, 95% CI 0.69-1.00).
In this large population-based cohort of LT registrants, the incidence of HCC among HCV patients has increased in the DAA era. Competing risks analysis suggests that this may be explained by changes in rates of LT and wait-list mortality in the HCV population during this time. (Hepatology 2018; 00:000-000).
接受直接作用抗病毒药物(DAA)治疗的丙型肝炎病毒(HCV)患者发生肝细胞癌(HCC)的风险一直存在争议。本研究旨在描述 DAA 时代接受肝移植(LT)患者的 HCC 发生率。使用移植受者科学登记处数据库确定了 2003 年 1 月至 2015 年 12 月期间因肝硬化而列入 LT 名单的个体。排除了在列入名单时或在 180 天内有 HCC 的患者。患者根据列入名单的日期分为三个时期:时期 1(2003-2010 年)、时期 2(2011-2013 年)和时期 3(2014-2015 年)。通过时期计算 HCC 的发生率,并使用发病率比(IRR)进行比较。使用 Cox 回归和竞争风险分析评估 HCC 与列入名单时期的关系,后者将死亡和 LT 视为竞争事件。在 48158 名合格的等待名单登记人中,有 3112 名(6.5%)在中位 493 天后获得 HCC 例外。在 20039 名 HCV 患者中,与时期 1 相比,时期 3 的 HCC 发生率高 49%(IRR 1.49,95%置信区间 [CI] 1.24-1.79)。在多变量分析中,与时期 1 相比,时期 3 的 HCC 发生风险更高(危险比 1.22,95%CI 1.01-1.48)。然而,在多变量竞争风险分析中,将死亡和 LT 视为新发 HCC 的竞争事件时,时期与 HCC 不再相关(亚分布危险比 0.83,95%CI 0.69-1.00)。
在这个基于人群的 LT 登记患者的大型队列中,DAA 时代 HCV 患者的 HCC 发生率有所增加。竞争风险分析表明,这可能是由于在此期间 HCV 人群的 LT 率和等待名单死亡率发生变化所致。(《肝脏病学》2018 年;000-000)。