肝癌，主要是肝细胞癌（HCC），是全球第三大导致癌症死亡的原因。有研究提出抗抑郁药物可能对癌症具有凋亡作用，但没有研究调查抗抑郁药物使用与HCC预后之间的关联。为了调查抗抑郁药物使用与HCC患者的死亡风险之间的关系，我们进行了这项基于人群的队列研究，分析的对象是台湾国家健康保险研究数据库，该数据库覆盖了台湾99%的人口并包含全面的医疗信息。通过诊断HCC的患者在1999年至2017年间的新发病例，我们于2023年6月进行分析。所有的HCC患者都进行了随访，以衡量总体和癌症特异性的死亡率。为了检查抗抑郁药物使用的时机是否影响与死亡的关联，我们研究了HCC诊断前和诊断后的抗抑郁药物使用情况。通过Cox比例风险回归分析，我们估计了抗抑郁药物使用与总体死亡率和癌症特异性死亡率之间的风险比（HR）和95%的可信区间（CI）。这项研究共涉及308,938名参与者，主要是年长者（131,991人，占42.7%的老年人≥65岁）和男性比例较高（202,589人，占65.6%）。HCC诊断前的抗抑郁药物使用与总体死亡率下降的风险无关（调整后HR 1.10，95% CI 1.08-1.12），也与癌症特异性死亡率下降的风险无关（调整后HR 1.06，95% CI 0.96-1.17）。然而，HCC诊断后的抗抑郁药物使用与总体死亡率下降的风险降低相关（调整后HR 0.69，95% CI 0.68-0.70），也与癌症特异性死亡率下降的风险降低相关（调整后HR 0.63，95% CI 0.59-0.68）。无论抗抑郁药物的类别还是合并症包括乙肝病毒或丙肝病毒感染、肝硬化和酒精使用障碍的亚组分析，观察到的关联性都是一致的。基于这项全国范围的队列研究，可以认为诊断后的抗抑郁药物使用可能与HCC患者的较低死亡率相关。进一步的随机临床试验评估应该被考虑。

Liver cancer, primarily hepatocellular carcinoma (HCC), is the third leading cause of cancer deaths worldwide. Although some studies have proposed that antidepressants may have apoptotic effects on cancer, no study has examined the association between antidepressant use and HCC prognosis.To investigate the association between antidepressant use and mortality risk in patients with HCC.This population-based cohort study analyzed Taiwan's National Health Insurance Research Database, which covers 99% of Taiwan's population and includes comprehensive medical information. Patients with a new diagnosis of HCC between 1999 and 2017 were identified. Analysis took place in June 2023.All patients with HCC were followed up until 2018 to measure overall and cancer-specific mortality. To examine whether the timing of antidepressant use influenced the association with mortality, antidepressant use was examined before and after HCC diagnosis. Cox proportional hazards regression was performed to estimate hazard ratios (HRs) and the 95% CIs for the association between antidepressant use and overall mortality and cancer-specific mortality.The study cohort comprised 308 938 participants, primarily consisting of older individuals (131 991 [42.7%] were aged ≥65 years) with a higher proportion of male individuals (202 589 [65.6%]). Antidepressant use before the diagnosis of HCC was not associated with lower risks of overall mortality (adjusted HR, 1.10; 95% CI, 1.08-1.12) and cancer-specific mortality (adjusted HR, 1.06; 95% CI, 0.96-1.17). However, antidepressant use after a diagnosis of HCC was associated with a lower risk of overall mortality (adjusted HR, 0.69; 95% CI, 0.68-0.70) and cancer-specific mortality (adjusted HR, 0.63; 95% CI, 0.59-0.68). The observed associations were consistent across subgroups with different antidepressant classes and comorbidities, including hepatitis B virus or hepatitis C virus infection, liver cirrhosis, and alcohol use disorders.Based on this nationwide cohort study, postdiagnosis antidepressant use may be associated with lower mortality in patients with HCC. Further randomized clinical trial evaluation should be considered.