Background and aims

Non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common liver disease worldwide. Modern lifestyles have been linked to this rise in prevalence with changes in rhythmic human behaviour emerging as a possible mechanism. We investigated how shift working patterns and chronotype were associated with hepatic fat fraction and NAFLD in 282,303 UK Biobank participants.

Methods

We stratified participants into day, irregular-shift, and permanent night-shift workers. We then utilised multiple methods of disease identification including (i) Dallas steatosis index (DSI), (ii) ICD10 codes, and (iii) hepatic proton density fat fraction (PDFF) and examined how shift work exposure impacted these variables. We further assessed the relationship of baseline chronotype with liver phenotypes using these same outcome measures.

Results

Compared to day workers, irregular-shift workers were more likely to have a high DSI (OR 1.29 (1.2–1.4)) after adjusting for major covariates with some attenuation after additional adjustment for BMI (OR 1.12 (1.03–1.22)). Likelihood of high DSI was also increased in permanent night-shift workers (OR 1.08 (0.9–1.29)) in the fully adjusted model. Mediator analysis revealed that BMI was a significant mediator of the shift work effect. Compared to participants with intermediate chronotype, those with extreme late chronotype had a higher likelihood of high DSI defined NAFLD (OR 1.45 (1.34–1.56)) and a higher likelihood of NAFLD/NASH by ICD10 code (OR 1.23 (1.09–1.39)). Hepatic PDFF was elevated in irregular shift workers, but not permanent night-shift workers.

Conclusions

Irregular-shift work and extreme late chronotype are associated with pathological liver fat accumulation, suggesting circadian misalignment may have an underlying pathogenic role. These findings have implications for health interventions to mitigate the detrimental effect of shift work.

中文翻译：

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在 282,303 名英国生物样本库参与者中，轮班工作和夜间作息时间与肝脂肪分数和非酒精性脂肪肝相关

背景和目标

非酒精性脂肪肝病（NAFLD）已迅速成为全球最常见的肝病。现代生活方式与这种患病率的上升有关，人类行为节奏的变化成为一种可能的机制。我们调查了 282,303 名英国生物银行参与者的轮班工作模式和时间类型与肝脂肪分数和 NAFLD 的关系。

方法

我们将参与者分为白班工人、不定期轮班工人和长期夜班工人。然后，我们利用多种疾病识别方法，包括 (i) 达拉斯脂肪变性指数 (DSI)、(ii) ICD10 代码和 (iii) 肝质子密度脂肪分数 (PDFF)，并研究了轮班工作暴露如何影响这些变量。我们使用这些相同的结果指标进一步评估了基线时间型与肝脏表型的关系。

结果

与日班工人相比，不规则轮班工人在调整主要协变量后更有可能具有较高的 DSI（OR 1.29 (1.2–1.4)），并且在额外调整 BMI 后出现一些衰减（OR 1.12 (1.03–1.22)）。在完全调整的模型中，长期夜班工人患高 DSI 的可能性也有所增加（OR 1.08 (0.9–1.29)）。中介分析显示，BMI 是轮班工作效应的显着中介变量。与中间时间型的参与者相比，极端晚时间型的参与者患高 DSI 定义的 NAFLD 的可能性更高（OR 1.45 (1.34–1.56)），并且根据 ICD10 代码患 NAFLD/NASH 的可能性更高（OR 1.23 (1.09–1.39)） 。不定期轮班工人的肝脏 PDFF 升高，但夜班工人的肝脏 PDFF 升高。

结论

不规则的轮班工作和极端晚睡与病理性肝脏脂肪堆积有关，表明昼夜节律失调可能具有潜在的致病作用。这些发现对减轻轮班工作有害影响的健康干预措施具有重要意义。