輪班工作與肝癌及代謝功能障礙相關脂肪肝 (MASLD)之關聯: 使用英國生物銀行的回顧性世代研

Abstract

背景 : 輪班工作是導致晝夜節律失調、代謝功能異常及多種慢性疾病的重要危險因子。部分研究指出輪班工作可能與代謝功能障礙相關脂肪性肝病（Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD）的發生有關，但其實際危害程度可能仍被低估。此外，目前輪班工作與致肝癌風險的證據仍然不足。本研究旨在探討輪班工作與新發肝癌及 MASLD 風險之間的關聯。 研究方法 : 本研究利用英國生物銀行（UK Biobank）資料進行回溯性世代研究（retrospective cohort study）。納入於招募時為受僱或自營作業，且具備完整輪班工作資料的參與者。輪班工作暴露狀況來自參與者自行填寫的問卷，將參與者區分為輪班工作者與非輪班工作者。新發肝癌與 MASLD 個案透過連結電子健康紀錄進行確認，包括基層醫療紀錄（primary care records）、住院醫療紀錄及癌症登錄資料。研究採用 Cox 比例風險迴歸模型（Cox proportional hazards regression model）評估風險比（Hazard Ratio, HR）及其 95% 信賴區間（Confidence Interval, CI），並調整人口學、社會經濟、生活型態及代謝相關因素等共變項。 研究結果 : 在納入分析的 285,397 名參與者中，17.3%（n = 49,352）從事輪班工作。在長達 16 年的追蹤期間內，共發現 4,819 例新發 MASLD 個案及 609 例新發肝癌個案，其發生率分別為每 10 萬人年 128.35 例及 16.02 例。在完整校正模型中，輪班工作者罹患 MASLD 的風險較非輪班工作者增加 16%（HR = 1.16，95% CI：1.06–1.28）。相較之下，輪班工作與新發肝癌之間未觀察到具有統計顯著性的關聯（HR = 1.13，95% CI：0.84–1.51)。 結論 : 本研究發現，輪班工作與新發 MASLD 風險顯著增加有關；然而目前並無足夠證據支持輪班工作與肝癌發生風險增加有關。研究結果顯示，非傳統工作時程可能透過干擾晝夜節律而對肝臟健康造成不利影響。未來仍需進行具有更詳細輪班工作暴露評估及更長追蹤期間的研究，以進一步釐清輪班工作與肝癌風險之間的關係。

Background: Shift work has been an emerging risk factor contributing to circadian disruption, metabolic dysfunction, and several chronic diseases. Some research has pointed toward a potential link between shift work and the onset of metabolic dysfunction-associated steatotic liver disease (MASLD), while the real hazards might be underestimated. In addition, the carcinogenic risks of shift work remain poorly understood. This study aimed to investigate the association between shift work and the risk of incident liver cancer and MASLD Methods: We utilized the UK Biobank to perform a retrospective cohort study. Participants reporting being in paid or self-employment at the time of recruitment and having available information on shift work status were included. Shift work exposure was self-reported and categorized as shift worker and non-shift worker. Incident liver cancer and MASLD cases were ascertained through linked electronic health records, including primary care records, hospital inpatient care records, and cancer registry data. Hazard ratios (HR) along with 95% confidence intervals (CI) were estimated using Cox proportional hazards regression models, and covariates related to demographic, socioeconomic, lifestyle, and metabolic factors were adjusted for. Results: Of the 285,397 employed participants included in the analysis, 17.3% (n = 49,352) were engaged in shift work. Over a 16-year follow-up period, 4,819 incident cases of MASLD and 609 incident cases of liver cancer were identified, corresponding to incidence rates of 128.35 and 16.02 per 100,000 person-years, respectively. In fully adjusted models, we found strong evidence that shift work was associated with a 16% higher risk of MASLD (HR: 1.16, 95% CI: 1.06–1.28). In contrast, no significant association was observed between shift work and incident liver cancer (HR: 1.13, 95% CI: 0.84–1.51). Conclusion: Our study found that shift work was associated with a significantly increased risk of incident MASLD; however, evidence supporting an increased risk of liver cancer was not statistically strong. These results indicate that non-traditional work schedules might negatively impact liver health, potentially through circadian disruption. Further studies with detailed shift work exposure assessments and longer follow-up are needed to clarify the relationship between shift work and liver cancer risk.