AASLD2018[93]亲脂性他汀类药物与肝细胞癌的风险 癌症和死亡率

StephenW

93
Lipophilic Statins and Risk of Hepatocellular
Carcinoma and Mortality: A Prospective,
Nationwide Population with Chronic Viral
Hepatitis
Tracey G Simon, Massachusetts General Hospital, Ann-Sofi
Duberg, Orebro University Hospital, Soo Aleman, Department
of Infectious Diseases, Karolinska University Hospital,
Hannes Hagström, Center for Digestive Diseases, Division of
Hepatology, Karolinska Institutet, Raymond T. Chung, Liver
Center and Gastrointestinal Division, Massachusetts General
Hospital and Harvard Medical School and Jonas F Ludvigsson,
Medical Epidemiology and Biostatistics, Karolinska Institutet
Background: In the U.S. and Europe, the incidence of
hepatocellular carcinoma (HCC) has tripled over the past
thirty years, and rates of HCC mortality are rising more
rapidly than for any other cancer. A body of epidemiological
evidence now suggests that for patients with chronic
hepatitis B virus (HBV) or hepatitis C virus (HCV), statins
may improve clinical outcomes and reduce HCC risk. Recent
experimental data further suggests that lipophilic statins (i.e.
atorvastatin, simvastatin, fluvastatin and lovastatin) may
prevent hepatocarcinogenesis more potently than hydrophilic
statins (i.e. pravastatin, rosuvastatin). However, in humans,
prospective data regarding the optimal statin type and
dose for effective HCC prevention are limited. Methods:
We conducted a nationwide, propensity score-matched
cohort study of 16,668 patients with confirmed chronic HBV
(n=3,906) or HCV (n=12,762) living in Sweden between
2005-2015, using prospectively-collected and updated data
from validated, nationwide Swedish Registers. Using the
Prescribed Drug Register, we defined lipophilic statin use or
hydrophilic statin use as a filled prescription for ≥30 cumulative
defined daily doses (cDDD) of the relevant statin type, and
data were updated monthly over the study follow-up. All HCC
cases and deaths were confirmed. Using Cox proportional
hazard modeling with time-varying exposures and covariates,
we estimated multivariable-adjusted subdistribution hazard
ratios (aHRs) for HCC and all-cause mortality, accounting
for competing risks. Results: Over a median follow-up of
96 months, we identified 606 cases of incident HCC and
1,664 deaths. Significantly lower HCC risk was observed
with lipophilic statin use, compared to non-use (aHR 0.56,
95% CI 0.33-0.80; number-needed-to-treat=23). This benefit
appeared dose-related: compared to non-users, the aHRs for
HCC were 0.78 (95% CI 0.51-1.09) for 30-299 cDDD, 0.57
(95% CI 0.50-0.65) for 300-599 cDDD, and 0.48 (95% CI 0.34-
0.62) for ≥600 cDDD (Ptrend among users <0.0001). Lipophilic statin
use was also associated with significantly lower risk of death
(aHR 0.73, 95%CI 0.72-0.75), in a dose-dependent manner
(Ptrend among users<0.0001). In contrast, hydrophilic statin use was
not associated with HCC risk reduction (aHR 1.01, 95%CI
0.81-1.88), or with a dose-dependent reduction in mortality
(Ptrend among users=0.52). Similarly, no significant association was
found with incident HCC risk, when non-statin lipid-lowering
medication users and non-users were compared (aHR 1.06,
95% CI 0.86-1.29). Conclusion: In this nationwide population
with chronic viral hepatitis, use of lipophilic but not hydrophilic
statins was associated with dose-dependent reductions in
risk for incident HCC and all-cause mortality. Our findings
support the potential incorporation of lipophilic statins into
HCC primary prevention strategies.

StephenW

个93
亲脂性他汀类药物与肝细胞癌的风险
癌症和死亡率：一个前景，
全国慢性病毒性人群
肝炎
Tracey G Simon，麻省总医院，Ann-Sofi
杜尔格，厄勒布鲁大学医院，Soo Aleman，Department
卡罗林斯卡大学医院传染病研究所，
HannesHagström，消化疾病中心
Hepatology，Karolinska Institutet，Raymond T. Chung，Liver
马萨诸塞州中心和胃肠科
医院和哈佛医学院和Jonas F Ludvigsson，
医学流行病学和生物统计学，卡罗林斯卡学院
背景：在美国和欧洲的发病率
过去，肝细胞癌（HCC）增加了两倍
三十年来，HCC死亡率正在上升
比任何其他癌症都快。一个流行病学的机构
现在的证据表明，对于慢性病患者
乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV），他汀类药物
可以改善临床结果并降低HCC风险。最近
实验数据进一步表明亲脂性他汀类药物（即
阿托伐他汀，辛伐他汀，氟伐他汀和洛伐他汀）可能
预防肝癌的发生比亲水性更强
他汀类药物（即普伐他汀，罗苏伐他汀）。然而，在人类中
关于最佳他汀类型和类似物的前瞻性数据
有效预防HCC的剂量有限。方法：
我们在全国范围内进行了一次倾向性评分
1668例确诊慢性HBV患者的队列研究
（n = 3,906）或HCV（n = 12,762）居住在瑞典之间
2005 - 2015年，使用前瞻性收集和更新的数据
来自经过验证的全国性瑞典登记册。使用
规定的药物注册，我们定义亲脂他汀的使用或
亲水性他汀类药物作为填充处方使用≥30累积
定义相关他汀类型的每日剂量（cDDD），和
每月通过研究随访更新数据。所有HCC
案件和死亡得到确认。使用Cox比例
具有时变暴露和协变量的危险模型，
我们估计了多变量调整的子分布危害
HCC的比率（aHRs）和全因死亡率，会计
竞争风险。结果：超过中位数随访
96个月，我们确定了606例HCC事件和
1,664人死亡。观察到显着降低的HCC风险
使用亲脂性他汀类药物，与非使用相比（aHR 0.56，
95％CI 0.33-0.80;数需要性治疗= 23）。这个好处
与剂量相关：与非使用者相比，aHRs为
HCC为0.78（95％CI 0.51-1.09），30-299cDDD，0.57
（95％CI 0.50-0.65）300-599 cDDD和0.48（95％CI 0.34-）
0.62）≥600cDDD（用户之间的Ptrend <0.0001）。亲脂性他汀类药物
使用也与显着降低的死亡风险有关
（aHR 0.73,95％CI 0.72-0.75），呈剂量依赖性
（用户之间的Ptrend <0.0001）。相反，使用亲水性他汀类药物
与HCC风险降低无关（aHR 1.01,95％CI
0.81-1.88），或具有剂量依赖性的死亡率降低
（用户之间的Ptrend = 0.52）。同样，没有重要的关联
发现HCC事件风险，非他汀类药物降脂时
药物使用者和非使用者进行了比较（aHR 1.06，
95％CI 0.86-1.29）。结论：在这个全国范围内的人口
与慢性病毒性肝炎，使用亲脂但不亲水
他汀类药物与剂量依赖性降低有关
发生HCC和全因死亡的风险。我们的发现
支持将亲脂性他汀类药物纳入其中
HCC一级预防策略。