Massimo Colombo讨论为什么应该向患有HCC风险的患者推荐小剂量

StephenW

Massimo Colombo on Why It May Be Time to Recommend Low-Dose Aspirin for Patients At Risk of HCC
Mounting research indicates risk reduction for vulnerable patients at risk, with no increased risk of bleeding
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    by Diana Swift
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With global rates of hepatocellular carcinoma (HCC) surging, Italian researchers including hepatologist Massimo Colombo, MD, of Humanitas Research Hospital in Rozzano, scanned the recent evidence and, based on their review, made a case for low-dose aspirin as an option for mitigating risk of HCC. Recent research has suggested that aspirin at <160 mg/day could be chemoprotective against HCC development and liver-related mortality in chronic hepatitis B and C patients, without increased risk of bleeding. The Italian review was published recently in Gastroenterology.

Colombo discussed the findings in the following interview.

What was the context in which your group undertook this look at aspirin and HCC?

Colombo:
Despite articulated public health interventions to contain world population exposure to risk factors for HCC, such as hepatitis B and C viruses, as well as increased access to effective hepatitis therapy with unprecedented cure rates, the incidence of this tumor is soaring globally.

In the United States, HCC is the fastest-increasing cause of cancer-related death, with a disproportionate burden in racial/ethnic minorities and people of low socioeconomic status. All in all, this advocates for additional approaches of prevention. Chemoprevention by low-dose aspirin is emerging as an attractive option.

What has the research to date shown about the impact of aspirin on various cancers?

Colombo:
Cohort and population studies have highlighted a reduction in both incidence and mortality for colorectal cancer and in incidence for hepatobiliary cancer, HCC, and, in the context of Lynch syndrome, for endometrial, ovarian, pancreatic, brain, small bowel, gall bladder, ureter, stomach, and kidney cancers. In the Nurses' Health Study, aspirin use after diagnosis of breast cancer was also associated with a reduction in death risk.

Did any of the findings in your current review come as a surprise?

Colombo:
While chemoprevention of HCC by aspirin was expected, following both experimental and epidemiological investigations, what we didn't fully expect was the finding of a reduction in liver-related mortality with low-dose aspirin in such a low-age population of patients 45 years or younger versus the reduction found for the 10-year older average age of Mediterranean patients. Also, quite surprising was the absence of increased bleeding risk.

Could you talk about the probable mechanisms of the protective action of aspirin?

Colombo:
Low-dose aspirin inactivates the immune pathological mechanisms of viral hepatitis that cause inflammation, regeneration, and transformation of liver cells. It suppresses the formation of platelet aggregates and the intrahepatic accumulation of pathogenic CD8+ T cells and other platelet-derived products potentially supporting tumor growth. These include platelet-derived growth factor, vascular endothelial growth factor, insulin-like growth factor, hepatocyte growth factor, and epidermal growth factor, as well as small molecules stimulating hepatocellular proliferation such as serotonin.

What effect would higher or longer doses have?

Colombo:
A dose-response relationship of aspirin in HCC chemoprevention has been highlighted in only a few studies. In the recent New England Journal of Medicine study by Simon et al., there was a duration-risk relationship, and the prevention of metastatic cancer has more often been reported in trials using high-dose aspirin at 300 mg daily.

Have any gastroenterological societies officially embraced low-dose aspirin for risk reduction?

Colombo:
Based on the preliminary 5-year data from the U.K.'s CAPP2 trial, the National Institute for Health and Care Excellence recommended offering aspirin for the prevention of bowel cancer in adults with Lynch syndrome. And the U.S. Preventive Services Task Force recommends initiating low-dose aspirin for the primary prevention of colorectal cancer in adults ages 50 to 59 years who are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years. The recommendation is conditional for persons ages 60 to 70 years, and aspirin is not recommended for patients older than 70 and younger than 50.

So what's the next step?

Colombo:
We need to do randomized controlled trials.

You can read a summary of the article here, and about the clinical implications of the study here.

No specific funding for this review was disclosed.

Colombo reported ties to Gilead Sciences, MSD, Roche, Bayer, Intercept, Wasserman, Target HCC, Exelixis, and Galapagos.

Co-author Guidotti reported relationships with Genenta Science, Epsilen Bio, and Gilead Sciences. La Vecchia disclosed ties to Teofarma.

    Primary Source
    Gastroenterology
    Source Reference: Guidotti LG, et al "Is it time to recommend low-dose aspirin treatment for the prevention of hepatocellular carcinoma?" Gastroenterology 2020; DOI: 10.1053/j.gastro.2020.09.007.

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StephenW

Massimo Colombo讨论为什么应该向患有HCC风险的患者推荐小剂量阿司匹林
越来越多的研究表明，对于处于危险中的脆弱患者，其风险有所降低，而出血的风险并未增加

    通过戴安娜·斯威夫特
    撰稿人

    此阅览室是MedPageToday®和Med Med Today之间的合作

随着全球肝细胞癌（HCC）比率的飙升，包括Rozzano Humanitas研究医院的肝病学家Massimo Colombo，MD在内的意大利研究人员对最近的证据进行了扫描，并根据他们的评论为低剂量阿司匹林提供了理由降低肝癌的风险。最近的研究表明，阿司匹林<160 mg / day可能对慢性乙型和丙型肝炎患者的HCC发生和肝脏相关的死亡具有化学保护作用，而不会增加出血的风险。意大利评论最近发表在胃肠病学上。

科伦坡在随后的采访中讨论了调查结果。

您的小组在什么情况下对阿司匹林和HCC进行了研究？

科伦坡：
尽管有明确的公共卫生干预措施可以遏制世界人口接触诸如乙型和丙型肝炎病毒之类的肝癌危险因素，以及以空前的治愈率获得有效的肝炎治疗的机会有所增加，但这种肿瘤的发病率在全球范围内仍在不断上升。

在美国，HCC是与癌症相关的死亡增长最快的原因，在种族/族裔少数群体和社会经济地位低下的人群中负担不成比例。总而言之，这提倡采取其他预防措施。低剂量阿司匹林的化学预防正在成为一种有吸引力的选择。

迄今为止，有关阿司匹林对各种癌症的影响的研究表明了什么？

科伦坡：
队列研究和人群研究强调了结直肠癌和肝胆癌，HCC的发病率和死亡率均降低，在Lynch综合征的情况下，子宫内膜，卵巢，胰腺，脑，小肠，胆囊，输尿管的发病率和死亡率均降低，胃癌和肾癌。在护士健康研究中，乳腺癌诊断后使用阿司匹林还可以降低死亡风险。

您当前评论中的任何发现是否令人惊讶？

科伦坡：
尽管经过实验和流行病学调查均预期使用阿司匹林对HCC进行化学预防，但我们并未完全期望发现在如此低年龄的45岁患者中，低剂量阿司匹林可降低肝脏相关死亡率或与地中海患者10岁平均年龄的减少相比更年轻。同样，令人惊讶的是没有增加的出血风险。

您能否谈谈阿司匹林保护作用的可能机制？

科伦坡：
小剂量阿司匹林可灭活引起肝细胞炎症，再生和转化的病毒性肝炎的免疫病理机制。它抑制血小板聚集体的形成以及致病性CD8 + T细胞和其他血小板衍生产物在肝内的积累，这些潜在支持肿瘤的生长。这些包括血小板衍生的生长因子，血管内皮生长因子，胰岛素样生长因子，肝细胞生长因子和表皮生长因子，以及刺激肝细胞增殖的小分子，例如血清素。

更高或更长的剂量会有什么作用？

科伦坡：
仅在少数研究中强调了阿司匹林在肝癌化学预防中的剂量反应关系。在西蒙等人最近进行的《新英格兰医学杂志》研究中，存在持续时间-风险关系，并且在每天使用300毫克大剂量阿司匹林的试验中，转移癌症的预防更为常见。

是否有任何胃肠病学学会正式采用低剂量阿司匹林来降低风险？

科伦坡：
根据英国CAPP2试验的5年初步数据，美国国立卫生与医疗保健研究院建议提供阿司匹林预防Lynch综合征成年人的肠癌。美国预防服务工作队建议在低年龄段50至59岁的成年人中启动低剂量阿司匹林用于大肠癌的预防，这些成年人的出血风险没有增加，预期寿命至少为10年，并且愿意每天服用小剂量阿司匹林至少10年。该建议是有条件的，适用于60至70岁的人群，不建议阿司匹林用于70岁以上和50岁以下的患者。
那么下一步是什么？

科伦坡：
我们需要进行随机对照试验。

您可以在此处阅读该文章的摘要，并在此处阅读该研究的临床意义。

没有透露此次审查的具体资金。

科伦坡报告了与吉利德科学，默沙东，罗氏，拜耳，Intercept，Wasserman，Target HCC，Exelixis和加拉帕戈斯的关系。

合著者Guidotti报告了与Genenta Science，Epsilen Bio和Gilead Sciences的关系。 La Vecchia透露了与Teofarma的关系。

     主要资源
     消化内科
     来源参考：Guidotti LG等人“现在是时候建议使用小剂量阿司匹林治疗预防肝细胞癌了吗？” 胃肠病学2020; DOI：10.1053 / j.gastro.2020.09.007。

StephenW

小心，咨询您的医生.