慢性乙型肝炎的阿司匹林和他汀類藥物：複雜

StephenW

Aspirin and Statins in Chronic Hepatitis B: It's Complicated

Emily Willingham

November 19, 2020

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For patients with chronic hepatitis B, the protective effects of aspirin against hepatocellular carcinoma (HCC) can vary with cirrhosis status and statin treatment, a pair of new studies finds.

One study showed that although aspirin is linked to a reduction in risk for HCC in these patients, comedication with statins could explain some of that effect. The other showed that cirrhosis dampens the risk-reduction benefit of aspirin.

Currently, there is a link between a reduction in HCC risk and aspirin or statins in patients with chronic hepatitis B, said investigator Won-Mook Choi, MD, PhD, from the University of Ulsan College of Medicine, in Seoul, Republic of Korea.

In one of their analyses, Choi and his colleagues teased out the contribution of each drug, and found that the decrease in HCC risk conferred by statins is similar whether or not patients also take aspirin.

"Only statins showed consistent and significant dose-dependent reductions in the risk of HCC, regardless of study design," said Choi, who presented the findings at The Liver Meeting 2020.

The second study, which looked at the association between aspirin and the risk for HCC in patients with and without cirrhosis, was presented by Heejoon Jang, MD, from the Seoul National University College of Medicine.

Aspirin was shown to be associated with a reduced risk for HCC, but cirrhosis "had a substantial effect on this association," erasing the benefit of aspirin, Jang reported.
Statins and Aspirin

Statins and aspirin are more likely to be prescribed together for patients with chronic hepatitis B but no cirrhosis, said Choi. For that reason, he and his colleagues analyzed data from the Korean National Health Insurance Service database from 2005 to 2015.

In their nested case–control analysis, 17,150 patients with HCC were matched for sex, age, and other factors to 817,675 patients without HCC. All participants had chronic hepatitis B without cirrhosis and had never received antiviral treatment.

The team also analyzed the incidence of HCC in two historic cohorts of patients with chronic hepatitis B but no cirrhosis, one consisting of 673,107 people who took aspirin and the other with 588,045 who took statins.

The nested case–control analysis showed an 11% risk reduction with aspirin use (adjusted odds ratio [OR], 0.89; 95% CI, 0.85 - 0.94) and a 61% risk reduction with statin use (adjusted OR, 0.39; 95% CI, 0.36 - 0.40). There was a dose-response effect with statins, but not with aspirin.

The historic cohort analysis showed a 33% reduction in the risk for HCC with aspirin (adjusted hazard ratio [HR], 0.67; 95% CI, 0.63 - 0.72) and a 67% reduction with statins (adjusted HR, 0.33; 95% CI, 0.30 - 0.37). However, stratified analyses by drug showed a statin benefit with or without aspirin (P < .001 for both), but no aspirin benefit without statins.
Cirrhosis and Aspirin

To assess the interaction between cirrhosis and aspirin, Jang and his colleagues identified 329,635 patients with chronic hepatitis B in the Korean National Health Insurance Service database.
A total of 20,200 had taken aspirin for at least 90 consecutive days, and the rest had never received antiplatelet therapy. Treated and untreated patients were matched for several factors, and HCC incidence was assessed after a median follow-up of 6.7 years.

Among the 2697 patients who developed HCC during follow-up, the cumulative incidence of HCC was significantly lower for those who took aspirin than for those who did not (P < .001). There was a 15% reduction in the risk for HCC in the aspirin group (adjusted HR, 0.85; 95% CI, 0.78 - 0.92).

However, in patients with cirrhosis, the benefit of aspirin disappeared. Patients without cirrhosis still had a 13% reduction in risk for HCC (adjusted HR, 0.87: 95% CI, 0.79 - 0.95). This group also had a slightly elevated risk for major bleeding (adjusted HR, 1.1; 95% CI, 1.03 - 1.28).

The findings from these two studies add to a growing body of literature that shows the promise of statins and aspirin, which are both readily available and relatively safe, said Amit Singal, MD, from the UT Southwestern Medical Center in Dallas, who was not involved with either study.

"The studies are relatively simple but really do tackle an area of immense need in the field," he said. Short of having higher-quality data, however, statins and aspirin aren't quite ready to become bespoke chemotherapies in the clinic, he added, although the results show promise for future randomized trials.

The subgroup analyses that looked at cirrhosis and the interplay of aspirin and statins can help with the planning of such trials, which "is really important for trial design, Singal noted.

He also pointed to studies that, unlike these results, have found a benefit of aspirin in patients with cirrhosis, underscoring the need for randomized trials. However, "each study does provide a data point that can help to inform those trials," he said.

Choi and Jang have disclosed no relevant financial relationships. Singal is a consultant for Genentech, Bayer, Eisai, Exelixis, Bristol-Myers Squibb, Roche, Glycotest, FujiFilm, GRAIL, and Exact Sciences, primarily in relation to HCC treatment and screening, not chemoprevention.

The Liver Meeting Digital Experience 2020: American Association for the Study of Liver Diseases (AASLD): Abstracts 137 and 159. Presented November 16, 2020.

StephenW

慢性乙型肝炎的阿司匹林和他汀類藥物：複雜

艾米麗·威靈厄姆

2020年11月19日

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兩項新的研究發現，對於慢性乙型肝炎患者，阿司匹林對肝細胞癌（HCC）的保護作用可能因肝硬化狀態和他汀類藥物治療而異。

一項研究表明，儘管阿司匹林可降低這些患者的肝癌風險，但他汀類藥物的喜劇可能可以解釋這種作用。另一項研究表明，肝硬化會降低阿司匹林的降低風險的益處。

韓國首爾蔚山大學醫學院的研究人員Won-Mook Choi醫師表示，目前，慢性乙型肝炎患者的HCC風險降低與阿司匹林或他汀類藥物之間存在聯繫。

在他們的一項分析中，Choi和他的同事戲弄了每種藥物的作用，發現無論患者是否也服用阿司匹林，他汀類藥物所致的HCC風險降低都是相似的。

Choi表示：“無論研究設計如何，只有他汀類藥物都能持續且顯著劑量依賴性地降低HCC風險，” Choi說，他在2020年肝臟會議上發表了研究結果。

首爾國立大學醫學院的Heejoon Jang醫師進行了第二項研究，研究了阿司匹林與肝硬化和非肝硬化患者中HCC風險之間的關係。

據Jang報導，阿司匹林顯示出與降低的HCC風險有關，但肝硬化“對該關聯具有實質性影響”，從而消除了阿司匹林的益處。
他汀類藥物和阿司匹林

Choi說，對於慢性乙型肝炎但無肝硬化的患者，他汀類藥物和阿司匹林更有可能一起開處方。因此，他和他的同事分析了韓國國民健康保險服務數據庫2005年至2015年的數據。

在他們的嵌套病例對照分析中，將17150例HCC患者的性別，年齡和其他因素與817675例非HCC患者進行了匹配。所有參與者均患有慢性乙型肝炎而無肝硬化，也從未接受過抗病毒治療。

該小組還分析了兩個歷史性隊列的慢性乙型肝炎但無肝硬化患者的肝癌發生率，其中一個患者包括服用阿司匹林的673107人，另一個服用他汀類藥物的588045人。

巢式病例對照分析顯示，使用阿司匹林可降低11％的風險（調整後的優勢比[OR]為0.89； 95％CI為0.85-0.94），使用他汀類藥物可降低61％的風險（調整後OR為0.39； 95％） CI，0.36-0.40）。他汀類藥物有劑量反應作用，但阿司匹林則無。

歷史隊列分析顯示，使用阿司匹林可將HCC風險降低33％（調整後的危險比[HR]，0.67； 95％CI，0.63-0.72），使用他汀類藥物，可將HCC的風險降低67％（調整後的HR，0.33； 95％CI ，0.30-0.37）。然而，按藥物進行的分層分析顯示，無論有或沒有阿司匹林，他汀類藥物獲益（兩者均P <.001），但沒有他汀類藥物則無阿司匹林益處。
肝硬化和阿司匹林

為了評估肝硬化和阿司匹林之間的相互作用，Jang和他的同事在韓國國民健康保險服務數據庫中確定了329635例慢性乙型肝炎患者。
總共有20,200人至少連續90天服用了阿司匹林，其餘的人從未接受過抗血小板治療。治療和未治療的患者在幾個因素上均匹配，中位隨訪6.7年後評估HCC發生率。

在隨訪期間發生肝癌的2697例患者中，服用阿司匹林的患者的HCC累積發生率明顯低於未服用阿司匹林的患者（P <.001）。阿司匹林組的HCC風險降低了15％（校正後的HR，0.85； 95％CI，0.78-0.92）。

但是，對於肝硬化患者，阿司匹林的益處消失了。沒有肝硬化的患者仍然有13％的HCC風險降低（校正後的HR，0.87：95％CI，0.79-0.95）。該組的大出血風險也略有升高（HR調整後為1.1； 95％CI為1.03-1.28）。

來自達拉斯的UT西南醫學中心的醫學博士阿米特·辛格（Amit Singal）表示，這兩項研究的發現增加了越來越多的文獻，這些文獻顯示了他汀類藥物和阿司匹林的前景，它們既容易獲得，又相對安全。與任何一項研究。

他說：“研究相對簡單，但確實可以解決該領域的巨大需求。”他補充說，他汀類藥物和阿司匹林缺乏高質量的數據，但還沒有準備好在臨床上成為定制的化學療法，儘管結果顯示了未來隨機試驗的希​​望。

Singal指出，研究肝硬化以及阿司匹林和他汀類藥物相互作用的亞組分析可以幫助規劃此類試驗，“對於試驗設計而言，這確實很重要。

他還指出，與這些結果不同的是，研究發現阿司匹林對肝硬化患者有益處，強調需要進行隨機試驗。不過，他說：“每項研究的確提供了一個數據點，可以幫助告知這些試驗。”

崔和張透露沒有相關財務關係。 Singal是Genentech，Bayer，Eisai，Exelixis，Bristol-Myers Squibb，Roche，Glycotest，FujiFilm，GRAIL和Exact Sciences的顧問，主要涉及HCC治療和篩查，而非化學預防。

2020年肝病會議數字體驗：美國肝病研究協會（AASLD）：摘要137和159。發表於2020年11月16日。