他汀类药物可降低无肝炎的HBV组的HCC风险

StephenW

[email protected]
       
2:51 AM (20 hours ago)
       
to nataphcv, HCV/HIV, [email protected], Natap
www.natap.org

Statins Tied to Lower HCC Risk in HBV Group Without Cirrhosis

AASLD The Liver Meeting Digital Experience, November 13-16, 2020

Mark Mascolini

A nationwide Korean case-control study linked aspirin and statin use to a lower risk of hepatocellular carcinoma (HCC) in antiviral-naive people with chronic HBV but without cirrhosis [1]. But further analysis cast doubt on the association of aspirin use with lower HCC risk, while the statin association with lower risk stayed strong.

Although aspirin and statins often get prescribed together, say University of Ulsan researchers who conducted this study, no work has assessed the combined impact of these antiinflammatory agents on HCC risk. The investigators suggested clinicians seem more likely to prescribe aspirin and statins for people with treated HBV but without cirrhosis, who have a lower HCC risk, than for people with cirrhosis, whose HCC risk runs higher.

To get a better understanding of the individual and combined impact of aspirin and statins on HCC development, a Korean team conducted a nationwide case-control study and then comparisons within historical cohorts. Study groups came from more than 834,000 people with data in the Korean National Health Insurance Service between 2005 and 2015.

For the case-control study the researchers defined cases as people admitted to the hospital with a first diagnosis of HCC. Randomly selected controls were people without HCC matched to cases in a 1-to-4 ratio for age, sex, cohort entry year, follow-up duration, and biennial general health exam status. The index date was the first diagnosis of chronic HBV infection according to ICD-10 code. To explore associations between aspirin and statins and HCC risk, the researchers used conditional logistic regression adjusted for age, sex, socioeconomic status, diabetes, hypertension, and concomitant medications.

To create historical cohorts, the researchers excluded people who took aspirin or a statin in the 2 years before the index date and used aspirin and statins irregularly during the period of the case-control study. The final aspirin historical cohort had 673,107 people and the statin historical cohort had 588,045. Follow-up ran from the index date to HCC diagnosis, death, liver transplant, antiviral therapy, or December 31, 2017.

The matched case-control analysis had 15,645 cases and 62,580 controls, 76% of them men, with ages averaging 53.7 years (cases) and 53.4 years (controls). About one quarter of cases and controls had diabetes, and about 44% had hypertension. Proportions of cases and controls taking aspirin were 19% and 24% and taking a statin 15% and 29%.

Compared with people who never used aspirin, those who ever used it had about 10% lower odds of HCC (adjusted odds ratio [aOR] 0.89, 95% confidence interval [CI] 0.85 to 0.94). The statin impact was greater: Compared with never-users, people who ever used statins had a 60% lower chance of HCC (aOR 0.39, 95% CI 0.36 to 0.40).

Compared with people who never used aspirin or a statin, HCC odds proved lower for those who used aspirin but not a statin (aOR 0.87, 95% CI 0.82 to 0.93) and lower still for those who used a statin but not aspirin (aOR 0.37, 95% CI 0.35 to 0.40). The odds ratio for this statin-only group was similar to the group that used both aspirin and a statin (aOR 0.34, 95% CI 0.32 to 0.37). Compared with no statin use, each higher cumulative statin dose further lowered odds of HCC. But taking more aspirin did not drive-down HCC risk in a dose-dependent manner.

The aspirin historical cohort had 59,672 cases and the same number of propensity score-matched controls. The statin historical cohort had 46,870 cases and the same number of propensity score-matched controls. In an unadjusted analysis of the aspirin historical cohort, aspirin-treated people had a higher risk of HCC than aspirin-untreated people (hazard ratio [HR] 1.16, 95% CI 1.09 to 1.23, P < 0.001). In a multivariable adjusted model, aspirin-treated people ran a lower HCC risk than aspirin-untreated people (HR 0.67, 95% CI 0.63 to 0.72, P < 0.001). In the unadjusted analysis of the statin historical cohort, statin takers had a 50% lower risk of HCC than statin-untreated people (HR 0.50, 95% CI 0.45 to 0.55, P < 0.001). In a multivariable adjusted model, statin-treated people had a two-thirds lower HCC risk than statin-untreated people (HR 0.33, 95% CI 0.30 to 0.27, P < 0.001).

Further analysis of the aspirin historical cohort determined that aspirin-untreated people treated with a statin (versus statin-untreated) had an HCC risk reduction similar to aspirin-treated people treated with a statin (versus statin-untreated): HRs 0.31 and 0.38 (P < 0.001 for both comparisons). In contrast, analysis of the statin historical cohort determined that statin-untreated people treated with aspirin (versus aspirin-untreated) and statin-treated people also treated with aspirin (versus aspirin-untreated) did not have a lower HCC risk: HRs 1.00 (P = 0.97) and 0.98 (P = 0.84). These results suggest that statins drive the HCC risk reduction with aspirin, but aspirin prophylaxis has no impact on HCC risk reduction with a statin.

The researchers concluded that statins, but not aspirin, “showed consistent and significant dose-dependent reductions in risk of HCC regardless of study design.” Because aspirin was not associated with lower HCC risk in stratified analyses, it appears that “the benefit of aspirin may have been confounded by statin use.”

Reference
1. Choi WM, Kim HJ, Ko MJ, et al. Association of aspirin and statin use with hepatocellular carcinoma risk in treatment-naïve non-cirrhotic patients with chronic hepatitis B. AASLD The Liver Meeting Digital Experience, November 13-16, 2020. Abstract 137.

StephenW

[email protected]

2:51 AM（20小时前）

致nataphcv，HCV / HIV，Natapindustry @ natap.org，Natap
www.natap.org

他汀类药物可降低无肝炎的HBV组的HCC风险

AASLD肝脏会议数字体验，2020年11月13日至16日

马克·马斯科利尼

韩国一项全国性病例对照研究将阿司匹林和他汀类药物的使用与患有慢性乙肝但无肝硬化的抗病毒天真的人的肝细胞癌（HCC）风险降低相关[1]。但是进一步的分析令人怀疑阿司匹林的使用与较低的HCC风险之间的关联，而他汀类药物与较低的HCC风险之间的关联仍然很强。

进行这项研究的蔚山大学研究人员说，尽管阿司匹林和他汀类药物经常一起开处方，但尚无任何工作评估这些抗炎药对HCC风险的综合影响。研究人员认为，与具有较高肝癌风险的肝硬化患者相比，临床医生似乎更愿意为患有乙肝病毒治疗但没有肝硬化的肝癌患者开具阿司匹林和他汀类药物。

为了更好地了解阿司匹林和他汀类药物对肝癌发展的个体和综合影响，一个韩国团队进行了一项全国病例对照研究，然后在历史人群中进行了比较。在2005年至2015年之间，来自834,000多人的研究小组获得了大韩民国国民健康保险服务的数据。

对于病例对照研究，研究人员将病例定义为首次诊断为HCC的入院患者。随机选择的对照组是没有HCC的患者，其年龄，性别，队列进入年份，随访时间和两年期一般健康检查状况的比例为1-4。根据ICD-10规范，索引日期是对慢性HBV感染的首次诊断。为了探索阿司匹林和他汀类药物与HCC风险之间的关系，研究人员使用了针对年龄，性别，社会经济状况，糖尿病，高血压和伴随用药进行调整的条件逻辑回归。

为了建立历史队列，研究人员排除了在索引日期之前的两年内服用阿司匹林或他汀类药物并且在病例对照研究期间不规律地使用阿司匹林和他汀类药物的人。最终的阿司匹林历史队列有673107人，而他汀类药物历史队列有588045人。随访时间从索引日期到HCC诊断，死亡，肝移植，抗病毒治疗或2017年12月31日。

匹配的病例对照分析有15645例病例和62580例对照，其中76％为男性，平均年龄为53.7岁（病例）和53.4岁（对照）。约四分之一的病例和对照患有糖尿病，约44％患有高血压。服用阿司匹林的病例和对照的比例分别为19％和24％，服用他汀类药物的比例为15％和29％。

与从未使用过阿司匹林的人相比，曾经使用过阿司匹林的人的HCC机率要低大约10％（调整后的机率[aOR]为0.89，95％的置信区间[CI]为0.85至0.94）。他汀类药物的影响更大：与从未使用过他汀类药物的人相比，曾经使用他汀类药物的人患HCC的机率降低了60％（aOR 0.39，95％CI 0.36至0.40）。

与从未使用过阿司匹林或他汀类药物的人相比，使用过阿司匹林但未使用他汀类药物的人的HCC几率更低（aOR 0.87，95％CI 0.82至0.93），而未使用过他汀类药物但未使用阿司匹林的人的HCC几率更低（aOR 0.37 ，95％CI 0.35至0.40）。仅使用他汀类药物的组的比值比与同时使用阿司匹林和他汀类药物的组的比值比（aOR 0.34，95％CI 0.32至0.37）。与不使用他汀类药物相比，每次服用更高的他汀类药物累积剂量都进一步降低了HCC发生几率。但是，服用更多的阿司匹林并不能以剂量依赖的方式降低肝癌的风险。

阿司匹林的历史队列有59,672例病例，并且倾向评分匹配的对照组人数相同。他汀类药物的历史队列有46,870例病例，并且倾向评分匹配对照的数量相同。在对阿司匹林历史队列的未经调整的分析中，接受阿司匹林治疗的人比未经阿司匹林治疗的人有更高的HCC风险（危险比[HR] 1.16，95％CI 1.09至1.23，P <0.001）。在多变量校正模型中，接受阿司匹林治疗的人比未经阿司匹林治疗的人发生HCC的风险更低（HR 0.67，95％CI 0.63至0.72，P <0.001）。在未经调整的他汀类药物历史人群分析中，他汀类药物服用者的肝癌风险比未经他汀类药物治疗的人低50％（HR 0.50，95％CI 0.45至0.55，P <0.001）。在多变量校正模型中，接受他汀类药物治疗的人的HCC风险比未经他汀类药物治疗的人低三分之二（HR 0.33，95％CI 0.30至0.27，P <0.001）。
对阿司匹林历史队列的进一步分析确定，用他汀类药物治疗的未接受阿司匹林治疗的人（未使用他汀类药物治疗）的HCC风险降低与接受他汀类药物治疗的阿司匹林治疗者（未使用他汀治疗的疾病）相似：HR 0.31和0.38（两次比较的P <0.001）。相比之下，对他汀类药物历史人群的分析确定，接受阿司匹林治疗的未接受他汀类药物治疗的人（未接受阿司匹林治疗的患者）和接受阿司匹林治疗的人（未经阿司匹林治疗的患者）也没有更低的HCC风险：HRs 1.00（ P = 0.97）和0.98（P = 0.84）。这些结果表明，他汀类药物可降低阿司匹林的HCC风险，但阿司匹林的预防对他汀类药物可降低HCC的风险没有影响。

研究人员得出结论，无论研究设计如何，他汀类药物（而非阿司匹林）均显示出HCC风险的剂量依赖性一致且显着降低。因为在分层分析中阿司匹林与较低的HCC风险无关，因此看来“使用他汀可能会混淆阿司匹林的益处。”

参考
1. Choi WM，Kim HJ，Ko MJ等。阿司匹林和他汀类药物的使用与初治的非肝硬化慢性乙型肝炎患者的肝细胞癌风险相关。AASLD肝脏会议数字体验，2020年11月13日至16日。摘要137。