恩替卡韦与替诺福韦治疗慢性乙型肝炎患者肝细胞癌的风险

StephenW

JAMA Oncol. 2018 Sep 27. doi: 10.1001/jamaoncol.2018.4070. [Epub ahead of print]
Risk of Hepatocellular Carcinoma in Patients Treated With Entecavir vs Tenofovir for Chronic Hepatitis B: A Korean Nationwide Cohort Study.
Choi J1, Kim HJ2, Lee J2, Cho S2, Ko MJ2, Lim YS1,2.
Author information

1
    Liver Center, Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
2
    Division for Healthcare Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Republic of Korea.

Abstract
Importance:

Entecavir and tenofovir disoproxil fumarate have comparable efficacy in achieving surrogate end points, including virologic response, and are equally recommended as first-line treatments for patients with chronic hepatitis B (CHB). However, it is unclear whether treatment with these drugs is associated with equivalent clinical outcomes, especially development of hepatocellular carcinoma (HCC).
Objective:

To compare entecavir and tenofovir in terms of the risk of HCC and death or liver transplant in patients with CHB infection.
Design, Setting, and Participants:

A nationwide historical population cohort study involving treatment-naive adult patients with CHB who started treatment with entecavir (n = 11 464) or tenofovir disoproxil fumarate (n = 12 692) between January 1, 2012, and December 31, 2014, using data from the Korean National Health Insurance Service database. As validation, a hospital cohort of patients with CHB treated with entecavir (n = 1560) or tenofovir (n = 1141) in a tertiary referral center between January 1, 2010, and December 31, 2016, were analyzed. Nationwide cohort data were retrieved from January 1, 2010, to December 31, 2016, and hospital cohort data from January 1, 2010, to October 31, 2017.
Main Outcomes and Measures:

Cumulative incidence rates of HCC and death and transplant rates.
Results:

Among the population cohort of 24 156, the mean (SD) age was 48.9 (9.8) years, and 15 120 patients (62.6%) were male. Among the hospital cohort of 2701, the mean (SD) age was 48.8 (10.5) years and 1657 patients (61.3%) were male. In the population cohort, the annual incidence rate of HCC was significantly lower in the tenofovir group (0.64 per 100 person-years [PY]) than in the entecavir group (1.06 per 100 PY). By multivariable-adjusted analysis, tenofovir therapy was associated with a significantly lower risk of HCC (hazard ratio [HR], 0.61; 95% CI, 0.54-0.70) and all-cause mortality or transplant (HR, 0.77; 95% CI, 0.65-0.92) compared with entecavir. The tenofovir group also showed a significantly lower risk of HCC in the 10 923-pair propensity score-matched population cohort (HR, 0.62; 95% CI, 0.54-0.70) and 869-pair propensity score-matched hospital cohort (HR, 0.68; 95% CI, 0.46-0.99) compared with the entecavir group.
Conclusions and Relevance:

This study suggests that tenofovir treatment was associated with a significantly lower risk of HCC compared with entecavir treatment in a population-based cohort of adults with CHB; these findings were validated in a hospital cohort. Given the poor prognosis of patients with HCC, these findings may have considerable clinical implications in prevention of this cancer in patients with CHB infection.

PMID:
    30267080
DOI:
    10.1001/jamaoncol.2018.4070

StephenW

JAMA Oncol。 2018年9月27日doi：10.1001 / jamaoncol.2018.4070。 [提前打印]
恩替卡韦与替诺福韦治疗慢性乙型肝炎患者肝细胞癌的风险：韩国全国队列研究。
Choi J1，Kim HJ2，Lee J2，Cho S2，Ko MJ2，Lim YS1,2。
作者信息

1
    韩国首尔蔚山医学院牙山医学中心消化内科肝脏中心。
2
    韩国首尔国家循证医疗合作机构医疗技术评估研究处。

抽象
重要性：

恩替卡韦和替诺福韦地索普西富马酸盐在实现替代终点方面具有相当的疗效，包括病毒学应答，同样推荐用于慢性乙型肝炎（CHB）患者的一线治疗。然而，尚不清楚用这些药物治疗是否与等效的临床结果相关，尤其是肝细胞癌（HCC）的发展。
目的：

比较恩替卡韦和替诺福韦在CHB感染患者中HCC和死亡或肝移植的风险。
设计，设置和参与者：

2012年1月1日至2014年12月31日期间，一项全国性的历史人群队列研究，包括治疗初始成人CHB患者，他们开始使用恩替卡韦（n = 11464）或替诺福韦地索普西富马酸盐（n = 12692）治疗，使用的数据来自韩国国民健康保险服务数据库。作为验证，分析了2010年1月1日至2016年12月31日期间在三级转诊中心接受恩替卡韦（n = 1560）或替诺福韦（n = 1141）治疗的CHB患者的医院队列。从2010年1月1日至2016年12月31日，以及2010年1月1日至2017年10月31日期间的医院队列数据检索全国范围的队列数据。
主要成果和措施：

HCC的累积发病率和死亡率和移植率。
结果：

在24156人群中，平均（SD）年龄为48.9（9.8）岁，15120名患者（62.6％）为男性。在2701名医院队列中，平均（SD）年龄为48.8（10.5）岁，1657名患者（61.3％）为男性。在人群中，替诺福韦组的HCC年发病率（0.64 / 100人年[PY]）明显低于恩替卡韦组（1.06 / 100 PY）。通过多变量校正分析，替诺福韦治疗与HCC风险显着降低（风险比[HR]，0.61; 95％CI，0.54-0.70）和全因死亡率或移植（HR，0.77; 95％CI， 0.65-0.92）与恩替卡韦相比。替诺福韦组在10923对倾向评分匹配的人群组（HR，0.62; 95％CI，0.54-0.70）和869对倾向评分匹配的医院队列中显示出显着较低的HCC风险（HR，0.68）与恩替卡韦组相比，95％CI，0.46-0.99）。
结论和相关性：

本研究表明，在基于人群的CHB成人队列中，与恩替卡韦治疗相比，替诺福韦治疗与HCC风险显着降低相关;这些发现在医院队列中得到了验证。鉴于HCC患者预后不良，这些发现可能对CHB感染患者预防这种癌症具有相当大的临床意义。

结论：
    30267080
DOI：
    10.1001 / jamaoncol.2018.4070