亲脂性他汀类药物与慢性病毒性肝炎患者肝细胞癌和死亡的

StephenW

Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis: Results From a Nationwide Swedish Population

Tracey G. Simon, MD, MPH; Ann-Sofi Duberg, MD, PhD; Soo Aleman, MD, PhD; Hannes Hagstrom, MD, PhD; Long H. Nguyen, MD, MPH; Hamed Khalili, MD, MPH; Raymond T Chung, MD; Jonas F. Ludvigsson, MD, PhD

Abstract
Background:

Whether statin type influences hepatocellular carcinoma (HCC) incidence or mortality in chronic hepatitis B or C virus infection is unknown.
Objective:

To assess the relationship between lipophilic or hydrophilic statin use and HCC incidence and mortality in a nationwide population with viral hepatitis.
Design:

Prospective propensity score (PS)–matched cohort.
Setting:

Swedish registers, 2005 to 2013.
Participants:

A PS-matched cohort of 16 668 adults (8334 who initiated statin use [6554 lipophilic and 1780 hydrophilic] and 8334 nonusers) among 63 279 eligible adults.
Measurements:

Time to incident HCC, ascertained from validated registers. Statin use was defined from filled prescriptions as 30 or more cumulative defined daily doses (cDDDs).
Results:

Compared with matched nonusers, 10-year HCC risk was significant lower among lipophilic statin users (8.1% vs. 3.3%; absolute risk difference [RD], −4.8 percentage points [95% CI, −6.2 to −3.3 percentage points]; Adjusted subdistribution hazard ratio [aHR], 0.56 [CI, 0.41 to 0.79]) but not hydrophilic statin users (8.0% vs. 6.8%; RD, −1.2 percentage points [CI, −2.6 to 0.4 percentage points]; aHR, 0.95 [CI, 0.86 to 1.08). The inverse association between lipophilic statins and HCC risk seems to be dose-dependent. Compared with nonusers, 10-year HCC risk was lowest with 600 or more lipophilic statin cDDDs (8.4% vs. 2.5%; RD, −5.9 percentage points [CI, −7.6 to −4.2 percentage points]; aHR, 0.41 [CI, 0.32 to 0.61]), and 10-year mortality was significantly lower in both lipophilic (15.2% vs. 7.3%; RD , −7.9 percentage points [CI, −9.6 to −6.2 percentage points]) and hydrophilic (16.0% vs. 11.5%; RD, −4.5 percentage points [CI, −6.0 to −3.0 percentage points ]) statin users.
Limitation:

Lack of lipid, fibrosis, or HCC surveillance data.
Conclusion:

In a nationwide viral hepatitis cohort, lipophilic statins were associated with significant reduced HCC incidence and mortality. An association between hydrophilic statins and reduced risk for HCC was not found. Further research is needed to determine whether lipophilic statin therapy is feasible for prevention of HCC.
Primary Funding Source:

None.

StephenW

亲脂性他汀类药物与慢性病毒性肝炎患者肝细胞癌和死亡的风险：来自全国瑞典人群的结果

Tracey G. Simon，医学博士，公共卫生硕士; Ann-Sofi Duberg，医学博士，博士; Soo Aleman，医学博士，博士; Hannes Hagstrom，医学博士，博士; Long H. Nguyen，MD，MPH; Hamed Khalili，医学博士，公共卫生硕士; Raymond T Chung，MD; Jonas F. Ludvigsson，医学博士，博士

抽象
背景：

他汀类药物是否影响肝细胞癌（HCC）发病率或慢性乙型肝炎或丙型肝炎病毒感染的死亡率尚不清楚。
目的：

评估全国性病毒性肝炎人群中亲脂性或亲水性他汀类药物使用与HCC发病率和死亡率之间的关系。
设计：

预期倾向评分（PS）匹配队列。
设置：

瑞典注册，2005年至2013年。
参与者：

在63 279名符合条件的成年人中，有16 668名成人的PS匹配队列（8334名使用他汀类药物[6554亲脂性和1780名亲水性]和8334名非使用者）。
测量：

从验证的寄存器确定HCC事件的时间。他汀类药物的使用定义为填充处方为30或更多累积定义的每日剂量（cDDD）。
结果：

与匹配的非使用者相比，亲脂性他汀类药物使用者的10年HCC风险显着降低（8.1％对3.3％;绝对风险差[RD]，-4.8个百分点[95％CI，-6.2至-3.3个百分点];调整后的子分布风险比[aHR]，0.56 [CI，0.41至0.79]）但不是亲水性他汀类药物使用者（8.0％vs。6.8％; RD，-1.2个百分点[CI，-2.6至0.4个百分点]; aHR，0.95 [CI，0.86至1.08）。亲脂性他汀类药物与HCC风险之间的反向关联似乎是剂量依赖性的。与非使用者相比，10年HCC风险最低，600或更多亲脂性他汀类药物IDDDs（8.4％vs。2.5％; RD，-5.9个百分点[CI，-7.6至-4.2个百分点]; aHR，0.41 [CI， 0.32至0.61]），10年死亡率显着低于亲脂性（15.2％对7.3％; RD，-7.9个百分点[CI，-9.6至-6.2个百分点]）和亲水性（16.0％对比11.5％; RD，-4.5个百分点[CI，-6.0至-3.0个百分点]）他汀类药物使用者。
局限性：

缺乏脂质，纤维化或HCC监测数据。
结论：

在全国范围的病毒性肝炎队列中，亲脂性他汀类药物与HCC发病率和死亡率显着降低有关。未发现亲水性他汀类药物与HCC风险降低之间的关联。需要进一步研究以确定亲脂性他汀类药物治疗是否可用于预防HCC。
主要资金来源：

没有。

StephenW

Lipophilic statins associated with significantly reduced liver cancer incidence and mortality

Embargoed news from Annals of Internal Medicine

American College of Physicians
Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information.

1. Lipophilic statins associated with significantly reduced liver cancer incidence and mortality

Abstract: http://annals.org/aim/article/doi/10.7326/M18-2753

URLs go live when the embargo lifts

Lipophilic statins were associated with significantly reduced hepatocellular carcinoma (HCC) incidence and mortality, but an association between hydrophilic statins and reduced risk for HCC was not found. Further research is needed to determine whether lipophilic statin therapy is feasible for prevention of HCC. Findings from a nationwide cohort study are published in Annals of Internal Medicine.

Approximately 500,000 cases of HCC are diagnosed worldwide each year, related primarily to chronic infection with hepatitis B virus or hepatitis C virus. In the U.S. and Europe, incidence of HCC has tripled since the 1970s and mortality is increasing more rapidly for HCC than for any other cancer. As such, there is an urgent need to identify effective primary prevention strategies. Whether statin type influences hepatocellular carcinoma (HCC) incidence or mortality is unknown.

Researchers from the Karolinska Institutet, Stockholm, Sweden and Harvard University, Boston, US, studied a nationwide Swedish registry of adults with viral hepatitis B or C to assess the relationship between lipophilic or hydrophilic statin use and HCC incidence and mortality. Compared with a matched cohort that did not use statins, lipophilic statin use was associated with substantially lower risk for incident HCC, all-cause death, and liver-related death. The apparent benefits of lipophilic statins were dose and duration-dependent, with the greatest reduction in HCC risk occurring after at least 600 cumulative defined daily doses (the equivalent of taking a moderate-dose statin for approximately 2 years). A similar association with reduced HCC risk was not found with hydrophilic statin use. According to the researchers, these findings confirm prior data linking statins with improved survival and reduced HCC risk in chronic liver disease.

Notes and media contacts: For an embargoed PDF please contact Lauren Evans at [email protected]. To speak with author Jonas F. Ludvigsson, MD, PhD, please contact Andreas Andersson at [email protected] or [email protected].

StephenW

亲脂性他汀类药物与肝癌发病率和死亡率显着降低有关

来自内科医学年鉴的禁播新闻

美国内科医师学会
下面请查看将在下一期“内科医学年鉴”上发表的新文章摘要。摘要无意替代完整的文章作为信息来源。

亲脂性他汀类药物与肝癌发病率和死亡率显着降低有关

摘要：http：//annals.org/aim/article/doi/10.7326/M18-2753

当禁运解除时，网址会上线

亲脂性他汀类药物与肝细胞癌（HCC）发病率和死亡率显着降低相关，但未发现亲水性他汀类药物与HCC风险降低之间存在关联。需要进一步研究以确定亲脂性他汀类药物治疗是否可用于预防HCC。一项全国性队列研究的结果发表在Annals of Internal Medicine上。

全世界每年诊断出大约500,000例HCC，主要与乙型肝炎病毒或丙型肝炎病毒的慢性感染有关。在美国和欧洲，自20世纪70年代以来，HCC的发病率增加了两倍，HCC的死亡率增长速度超过任何其他癌症。因此，迫切需要确定有效的一级预防战略。他汀类药物是否影响肝细胞癌（HCC）的发病率或死亡率尚不清楚。

来自瑞典斯德哥尔摩Karolinska研究所和美国波士顿哈佛大学的研究人员研究了一个全国性的瑞典成人病毒性乙型肝炎或丙型肝炎登记处，以评估亲脂性或亲水性他汀类药物使用与HCC发病率和死亡率之间的关系。与不使用他汀类药物的匹配队列相比，使用亲脂性他汀类药物可显着降低发生HCC，全因死亡和肝脏相关死亡的风险。亲脂性他汀类药物的明显益处是剂量和持续时间依赖性，在至少600次累积定义的每日剂量（相当于服用中等剂量他汀类药物约2年）后发生HCC风险的最大降低。使用亲水性他汀类药物时未发现类似的降低HCC风险的相关性。据研究人员称，这些研究结果证实了先前的数据将他汀类药物与慢性肝病患者的生存率和HCC风险降低联系起来。

笔记和媒体联系人：有关禁运的PDF，请通过[email protected]联系Lauren Evans。若要与作者Jonas F. Ludvigsson，医学博士，博士，请联系Andreas Andersson，电子邮件地址为[email protected]或[email protected]。