From the Division of Gastroenterology and Hepatology (T.G.S., R.T.C., A.T.C.) and the Clinical and Translational Epidemiology Unit (T.G.S., A.T.C.), Department of Medicine, Massachusetts General Hospital, Harvard Medical School (T.G.S., R.T.C., A.T.C.), Broad Institute (R.T.C., A.T.C.), and the Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health (A.T.C.) - all in Boston; the Department of Infectious Diseases, School of Medical Sciences, Faculty of Medicine and Health (A.-S.D.), and the Department of Pediatrics (J.F.L.), Örebro University Hospital, Örebro, and the Department of Infectious Diseases, Karolinska University Hospital (S.A.), the Department of Medicine Huddinge (S.A.), and the Department of Medical Epidemiology and Biostatistics (J.F.L.), Karolinska Institutet, Stockholm - all in Sweden; and the Department of Medicine, Columbia University College of Physicians and Surgeons, New York (J.F.L.).
N Engl J Med. 2020 Mar 12;382(11):1018-1028. doi: 10.1056/NEJMoa1912035.
More information is needed about the long-term effects of low-dose aspirin (≤160 mg) on incident hepatocellular carcinoma, liver-related mortality, and gastrointestinal bleeding in persons with chronic hepatitis B or hepatitis C virus infection.
Using nationwide Swedish registries, we identified all adults who received a diagnosis of chronic hepatitis B or hepatitis C from 2005 through 2015 and who did not have a history of aspirin use (50,275 patients). Patients who were starting to take low-dose aspirin (14,205 patients) were identified by their first filled prescriptions for 90 or more consecutive doses of aspirin. We constructed a propensity score and applied inverse probability of treatment weighting to balance baseline characteristics between groups. Using Cox proportional-hazards regression modeling, we estimated the risk of hepatocellular carcinoma and liver-related mortality, accounting for competing events.
With a median of 7.9 years of follow-up, the estimated cumulative incidence of hepatocellular carcinoma was 4.0% among aspirin users and 8.3% among nonusers of aspirin (difference, -4.3 percentage points; 95% confidence interval [CI], -5.0 to -3.6; adjusted hazard ratio, 0.69; 95% CI, 0.62 to 0.76). This inverse association appeared to be duration-dependent; as compared with short-term use (3 months to <1 year), the adjusted hazard ratios were 0.90 (95% CI, 0.76 to 1.06) for 1 to less than 3 years of use, 0.66 (95% CI, 0.56 to 0.78) for 3 to less than 5 years of use, and 0.57 (95% CI, 0.42 to 0.70) for 5 or more years of use. Ten-year liver-related mortality was 11.0% among aspirin users and 17.9% among nonusers (difference, -6.9 percentage points [95% CI, -8.1 to -5.7]; adjusted hazard ratio, 0.73 [95% CI, 0.67 to 0.81]). However, the 10-year risk of gastrointestinal bleeding did not differ significantly between users and nonusers of aspirin (7.8% and 6.9%, respectively; difference, 0.9 percentage points; 95% CI, -0.6 to 2.4).
In a nationwide study of patients with chronic viral hepatitis in Sweden, use of low-dose aspirin was associated with a significantly lower risk of hepatocellular carcinoma and lower liver-related mortality than no use of aspirin, without a significantly higher risk of gastrointestinal bleeding. (Funded by the National Institutes of Health and others.).
我们需要更多关于低剂量阿司匹林（≤160mg）对慢性乙型肝炎或丙型肝炎病毒感染患者的肝细胞癌、肝脏相关死亡率和胃肠道出血的长期影响的信息。
利用全国性的瑞典登记处，我们确定了所有在 2005 年至 2015 年期间被诊断为慢性乙型肝炎或丙型肝炎且无阿司匹林使用史的成年人（50275 例）。通过他们首次服用连续 90 剂或以上的阿司匹林处方，确定开始服用低剂量阿司匹林的患者（14205 例）。我们构建了一个倾向评分，并应用逆概率治疗加权来平衡组间的基线特征。使用 Cox 比例风险回归模型，我们估计了肝细胞癌和肝脏相关死亡率的风险，同时考虑了竞争事件。
中位随访 7.9 年，阿司匹林使用者的肝细胞癌累积发生率估计为 4.0%，而非阿司匹林使用者为 8.3%（差异为-4.3 个百分点；95%置信区间[CI]为-5.0 至-3.6；调整后的危险比为 0.69；95%CI 为 0.62 至 0.76）。这种负相关似乎与持续时间有关；与短期使用（3 个月至<1 年）相比，使用 1 至<3 年、3 至<5 年和 5 年以上的调整后的危险比分别为 0.90（95%CI 为 0.76 至 1.06）、0.66（95%CI 为 0.56 至 0.78）和 0.57（95%CI 为 0.42 至 0.70）。阿司匹林使用者的 10 年肝脏相关死亡率为 11.0%，而非使用者为 17.9%（差异为-6.9 个百分点[95%CI 为-8.1 至-5.7]；调整后的危险比为 0.73[95%CI 为 0.67 至 0.81]）。然而，阿司匹林使用者和非使用者的 10 年胃肠道出血风险差异无统计学意义（分别为 7.8%和 6.9%；差异为 0.9 个百分点；95%CI 为 0.6 至 2.4）。
在瑞典的一项全国性慢性病毒性肝炎患者研究中，与不使用阿司匹林相比，低剂量阿司匹林的使用与肝细胞癌风险显著降低和肝脏相关死亡率降低相关，而胃肠道出血风险无显著增加。（由美国国立卫生研究院等资助）。
