PDF(Pubmed)
Abstract：
BACKGROUND: Paracetamol induces hepatotoxicity and subsequent liver injury, which may increase the risk of liver cancer, but epidemiological evidence remains unclear. We conducted this study to evaluate the association between paracetamol use and the risk of liver cancer.
METHODS: This prospective study included 464,244 participants free of cancer diagnosis from the UK Biobank. Incident liver cancer was identified through linkage to cancer and death registries and the National Health Service Central Register using the International Classification of Diseases (ICD)-10 codes (C22). An overlap-weighted Cox proportional hazards model was utilized to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of liver cancer associated with paracetamol use. The number needed to harm (NNH) was calculated at 10 years of follow-up.
RESULTS: During a median of 12.6 years of follow-up, 627 cases of liver cancer were identified. Paracetamol users had a 28% higher risk of liver cancer than nonusers (HR 1.28, 95% CI 1.06-1.54). This association was robust in several sensitivity analyses and subgroup analyses, and the quantitative bias analysis indicated that the result remains sturdy to unmeasured confounding factors (E-value 1.88, lower 95% CI 1.31). The NNH was 1106.4 at the 10 years of follow-up.
CONCLUSIONS: The regular use of paracetamol was associated with a higher risk of liver cancer. Physicians should be cautious when prescribing paracetamol, and it is recommended to assess the potential risk of liver cancer to personalize the use of paracetamol.
METHODS: This prospective study included 464,244 participants free of cancer diagnosis from the UK Biobank. Incident liver cancer was identified through linkage to cancer and death registries and the National Health Service Central Register using the International Classification of Diseases (ICD)-10 codes (C22). An overlap-weighted Cox proportional hazards model was utilized to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of liver cancer associated with paracetamol use. The number needed to harm (NNH) was calculated at 10 years of follow-up.
RESULTS: During a median of 12.6 years of follow-up, 627 cases of liver cancer were identified. Paracetamol users had a 28% higher risk of liver cancer than nonusers (HR 1.28, 95% CI 1.06-1.54). This association was robust in several sensitivity analyses and subgroup analyses, and the quantitative bias analysis indicated that the result remains sturdy to unmeasured confounding factors (E-value 1.88, lower 95% CI 1.31). The NNH was 1106.4 at the 10 years of follow-up.
CONCLUSIONS: The regular use of paracetamol was associated with a higher risk of liver cancer. Physicians should be cautious when prescribing paracetamol, and it is recommended to assess the potential risk of liver cancer to personalize the use of paracetamol.
摘要：
背景：扑热息痛诱导肝毒性和随后的肝损伤，这可能会增加肝癌的风险，但流行病学证据尚不清楚.我们进行了这项研究，以评估扑热息痛的使用和肝癌的风险之间的关联。
方法：这项前瞻性研究包括464,244名来自英国生物库的无癌症诊断的参与者。通过使用国际疾病分类（ICD）-10代码（C22）与癌症和死亡登记处以及国家卫生服务中央登记处的联系来确定肝癌。重叠加权Cox比例风险模型用于计算与扑热息痛使用相关的肝癌风险的风险比（HR）和95％置信区间（CI）。在10年的随访中计算了伤害所需的数量（NNH）。
结果：在12.6年的中位随访期间，共确诊肝癌627例。扑热息痛使用者患肝癌的风险比非使用者高28％（HR1.28，95％CI1.06-1.54）。这种关联在几个敏感性分析和亚组分析中是稳健的，定量偏倚分析表明，结果与未测量的混杂因素（E值1.88，低于95％CI1.31）仍然坚固。随访10年NNH为1106.4。
结论：定期使用扑热息痛与肝癌的风险更高相关。医生在处方扑热息痛时应该谨慎，建议评估肝癌的潜在风险，以个性化使用扑热息痛。
方法：这项前瞻性研究包括464,244名来自英国生物库的无癌症诊断的参与者。通过使用国际疾病分类（ICD）-10代码（C22）与癌症和死亡登记处以及国家卫生服务中央登记处的联系来确定肝癌。重叠加权Cox比例风险模型用于计算与扑热息痛使用相关的肝癌风险的风险比（HR）和95％置信区间（CI）。在10年的随访中计算了伤害所需的数量（NNH）。
结果：在12.6年的中位随访期间，共确诊肝癌627例。扑热息痛使用者患肝癌的风险比非使用者高28％（HR1.28，95％CI1.06-1.54）。这种关联在几个敏感性分析和亚组分析中是稳健的，定量偏倚分析表明，结果与未测量的混杂因素（E值1.88，低于95％CI1.31）仍然坚固。随访10年NNH为1106.4。
结论：定期使用扑热息痛与肝癌的风险更高相关。医生在处方扑热息痛时应该谨慎，建议评估肝癌的潜在风险，以个性化使用扑热息痛。
