阿司匹林可預防乙肝患者的肝癌，但如果肝硬化則不能

StephenW

Aspirin Prevents HCC in People With HBV, But Not if They Have Cirrhosis

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

Mark Mascolini

In a nationwide Korean analysis of people with chronic HBV, those prescribed aspirin ran a lower risk of hepatocellular carcinoma (HCC) and liver mortality [1]. But aspirin did not protect people who already had cirrhosis in this matched comparison of thousands of pairs with or without an aspirin prescription.

Studies exploring the HCC-preventing potential of aspirin in people with viral hepatitis are huge, multilayered, and sometimes contradictory. A nationwide 8-year study of people in Sweden with chronic HBV or HCV linked low-dose aspirin to a significantly lower risk of HCC or liver-related death, with no higher risk of gastrointestinal bleeding [2]. A nationwide Korean case-control study initially found a lower HCC risk with aspirin or statins in HBV patients without cirrhosis [3]. But aspirin’s protective effect disappeared in further analyses, in which statin use appeared to confound the impact of aspirin.

Like the Korean aspirin-statin analysis [3], the Korean aspirin study drew data from people covered in the Korean National Health Insurance Service database, in this case from January 2002 through December 2017 [1]. The researchers included people with chronic HBV infection and excluded those with HCV, HIV, no health exam data, or a cancer diagnosis or major bleeding before the index date. They defined treated people as those prescribed aspirin for at least 90 consecutive days and untreated people as those never prescribed any antiplatelet. The index date was 180 days after the first aspirin prescription for the treated group and the first health exam date for the untreated group.

The researchers matched each aspirin-treated person with one untreated person by age, sex, total cholesterol, serum glucose or history of diabetes, body mass index, blood pressure or history of hypertension, AST, ALT, GTP, liver cirrhosis, decompensated cirrhosis, antiviral agent, metformin, statin,  and anticoagulant.

That exercise yielded 19,003 aspirin-treated people and 19,003 people never prescribed an antiplatelet drug. There were 16,507 pairs without cirrhosis and 2479 pairs with cirrhosis. Because of matching, the overall treated and untreated groups were similar in age (55 and 54), proportions of men (75.4% and 75.8%), and body mass index (25.1 and 25.1 kg/m2). The treated group had a minimally but significantly lower proportion with cirrhosis (13.2% vs 13.3%, P = 0.004) and a small but significantly lower proportion who got antiviral therapy (13.5% vs 13.8%, P = 0.009).

Through a median 6.7 years of follow-up, HCC developed in 2697 people. Those prescribed aspirin had a 15% lower risk of HCC (adjusted hazard ratio [aHR] 0.85, 95% confidence interval [CI] 0.78 to 0.92, P < 0.001). The lower risk with prophylactic aspirin held true in people without cirrhosis (aHR 0.87, 95% CI 0.79 to 0.95, P < 0.001). But limiting the analysis to people with cirrhosis completely wiped out aspirin’s protective effect against HCC (aHR 1.00, 95% CI 0.85 to 1.18, P = 0.51).

In the overall population, aspirin prophylaxis cut the risk of liver-related death 20% (aHR 0.80, 95% CI 0.71 to 0.90, P < 0.001). Again that protective effect held firm in people without cirrhosis (aHR 0.84, 95% CI 0.73 to 0.97, P = 0.001) but not in those with cirrhosis (aHR 0.91, 95% CI 0.72 to 1.1, P = 0.10).

In the whole study group, an aspirin prescription inflated the risk of major bleeding almost 10%, but that association lacked statistical significance (aHR 1.09, 95% CI 0.99 to 1.21, P = 0.15). Aspirin did significantly swell the risk of major bleeding in people without cirrhosis (aHR 1.15, 95% CI 1.03 to 1.28, P = 0.03) but not in those with cirrhosis (aHR 1.05, 95% CI 0.84 to 1.31, P = 0.64).

The researchers concluded that aspirin is associated with a lower risk of HCC in people with chronic HBV infection, but not if they already have cirrhosis. Having cirrhosis also erases the lower risk of liver mortality seen in people taking aspirin.

References
1. Jang H, Lee YB, Moon H, et al. Association of aspirin with hepatocellular carcinoma in patients with chronic hepatitis B with or without cirrhosis. AASLD The Liver Meeting Digital Experience, November 13-16, 2020. Abstract 159.
2. Simon TG, Duberg AS, Aleman S, Chung RT, Chan AT, Ludvigsson JF. Association of aspirin with hepatocellular carcinoma and liver-related mortality. N Engl J Med. 2020;382:1018-1028. doi: 10.1056/NEJMoa1912035.
3. Choi WM, Kim HJ, Ko MJ, et al. Association of aspirin and statin use with hepatocellular carcinoma risk in treatment-naive non-cirrhotic patients with chronic hepatitis B. AASLD The Liver Meeting Digital Experience, November 13-16, 2020. Abstract 137. (Reported separately by NATAP.)

StephenW

阿司匹林可預防乙肝患者的肝癌，但如果肝硬化則不能

AASLD肝臟會議數字體驗，2020年11月13日至16日

馬克·馬斯科利尼

在韓國對慢性乙型肝炎患者的一項全國性分析中，那些服用阿司匹林的人罹患肝細胞癌（HCC）和肝死亡率的風險較低[1]。但在成千上萬對使用或不使用阿司匹林處方的配對中，阿司匹林不能保護已經患有肝硬化的人。

探索阿司匹林在病毒性肝炎患者中預防肝癌的潛力的研究龐大，多層次，有時是相互矛盾的。一項對瑞典患有慢性HBV或HCV的人進行的為期8年的全國性研究將低劑量阿司匹林與明顯降低的HCC或與肝臟相關的死亡風險聯繫起來，沒有更高的胃腸道出血風險[2]。韓國一項全國性病例對照研究最初發現，在沒有肝硬化的HBV患者中，使用阿司匹林或他汀類藥物可降低HCC風險[3]。但是阿司匹林的保護作用在進一步的分析中消失了，在他汀類藥物的使用中似乎混淆了阿司匹林的作用。

像韓國阿司匹林-他汀類藥物分析[3]一樣，韓國阿司匹林研究從2002年1月至2017年12月韓國國民健康保險服務數據庫中的人群中提取數據[1]。研究人員包括患有慢性HBV感染的人，但排除了在索引日期之前患有HCV，HIV，無健康檢查數據，癌症診斷或重大出血的人。他們將接受治療的人定義為至少連續90天服用阿司匹林的人，將未治療的人定義為從未服用過抗血小板藥的人。索引日期是治療組首次服用阿司匹林處方後180天，未治療組首次接受健康檢查日期。

研究人員根據年齡，性別，總膽固醇，血糖或糖尿病史，體重指數，血壓或高血壓病史，AST，ALT，GTP，肝硬化，失代償性肝硬化，將每位接受阿司匹林治療的患者與一個未經治療的患者進行匹配。抗病毒藥，二甲雙胍，他汀類藥物和抗凝劑。

這項運動使19,003名接受阿司匹林治療的人和19,003名從未開過抗血小板藥的人。無肝硬化的有16507對，有肝硬化的有2479對。由於匹配，總體上治療組和未治療組的年齡（55歲和54歲），男性比例（75.4％和75.8％）以及體重指數（25.1和25.1 kg / m2）相似。治療組肝硬化的比例最低，但顯著較低（13.2％vs 13.3％，P = 0.004），接受抗病毒治療的比例很小但顯著較低（13.5％vs 13.8％，P = 0.009）。

通過平均6.7年的隨訪，HCC在2697人中發展。那些服用阿司匹林的人患肝癌的風險降低了15％（調整後的危險比[aHR]為0.85，95％的置信區間[CI]為0.78至0.92，P <0.001）。在沒有肝硬化的人群中，預防性阿司匹林的風險較低（aHR 0.87，95％CI 0.79至0.95，P <0.001）。但是將分析僅限於肝硬化患者完全消除了阿司匹林對肝癌的保護作用（aHR 1.00，95％CI 0.85至1.18，P = 0.51）。

在總的人群中，阿司匹林預防可將與肝有關的死亡風險降低20％（aHR 0.80，95％CI 0.71至0.90，P <0.001）。同樣，該保護作用在沒有肝硬化的患者中保持牢固（aHR 0.84，95％CI 0.73至0.97，P = 0.001），但在患有肝硬化的患者中則沒有（aHR 0.91，95％CI 0.72至1.1，P = 0.10）。

在整個研究組中，阿司匹林處方可增加大出血風險近10％，但這種關聯缺乏統計學意義（aHR 1.09，95％CI 0.99至1.21，P = 0.15）。阿司匹林確實顯著增加了無肝硬化患者的大出血風險（aHR 1.15，95％CI 1.03至1.28，P = 0.03），而對於患有肝硬化的患者則沒有（aHR 1.05，95％CI 0.84至1.31，P = 0.64）。

研究人員得出結論，阿司匹林與慢性HBV感染者的HCC風險較低相關，但如果他們已經患有肝硬化則不相關。肝硬化也消除了服用阿司匹林的人出現肝臟死亡的風險降低。

參考文獻
1. Jang H，Lee YB，Moon H等。阿司匹林與慢性乙型肝炎合併或不合併肝硬化的患者的關聯。 AASLD肝臟會議數字體驗，2020年11月13日至16日。摘要159。
2. Simon TG，Duberg AS，Aleman S，Chung RT，Chan AT，Ludvigsson JF。阿司匹林與肝細胞癌和肝相關死亡率的關聯。 N Engl J Med。 2020; 382：1018-1028。 doi：10.1056 / NEJMoa1912035。
3. Choi WM，Kim HJ，Ko MJ等。在未接受過治療的非肝硬化慢性乙型肝炎患者中，阿司匹林和他汀類藥物的使用與肝癌風險的關聯。AASLD肝臟會議數字體驗，2020年11月13日至16日。摘要137.（由NATAP另行報告）。