Accumulating evidence has supported that mild elevated total bilirubin exerts antioxidant and anti-inflammatory properties in multiple metabolic diseases. We aimed to explore the association of circulating total bilirubin concentration with non-alcoholic fatty liver disease (NAFLD) risk and all-cause mortality and examine the potential nonlinear relationships between them. We used nationally representative data from the National Health and Nutrition Examination Survey (NHANES). NAFLD was assessed using the fatty liver index (FLI) and United States fatty liver index (USFLI), respectively. A total of 35 912 and 17 329 participants were included in FLI-NAFLD (case with NAFLD was diagnosed by FLI) and USFLI-NAFLD (case with NAFLD was diagnosed by USFLI) groups, respectively. The mean age of total population was 46.25 years, and 48.51% were male. Compared to participants with lowest quintile of total bilirubin concentration, those with highest quintile had lower risk of NAFLD in both FLI-NAFLD (OR: 0.48, 95% CI: 0.40, 0.59) and USFLI-NAFLD (OR: 0.55, 95% CI: 0.43, 0.70) groups. Compared to participants with lowest quintile of total bilirubin concentration, the association between total bilirubin concentration and all-cause mortality was not significant among those with highest quintile of total bilirubin concentration (HR: 0.89, 95% CI: 0.66, 1.20). The restricted spline curves showed the nonlinear U-shaped association of total bilirubin concentration with NAFLD risk and all-cause mortality. The segmented linear regression analysis showed negative associations between total bilirubin concentration and risk of NAFLD in both FLI-NAFLD (OR: 0.94, 95% CI: 0.93, 0.95) and USFLI-NAFLD (OR: 0.95, 95% CI: 0.93, 0.96) groups when total bilirubin concentration was below the turning point (FLI-NAFLD: 18.81 μmol/L; USFLI-NAFLD: 15.39 μmol/L) and these associations were not significant when total bilirubin concentration was higher than the turning point. Furthermore, all-cause mortality decreased (OR: 0.97, 95%CI: 0.95, 1.00) with increased total bilirubin concentration up to the turning point (11.97 μmol/L), and then all-cause mortality increased with increasing total bilirubin concentration (OR: 1.03, 95%CI: 1.02, 1.04). We found that higher circulating total bilirubin concentration within the physiological range was associated with decreased risk of NAFLD and all-cause mortality among NAFLD patients.

中文翻译：

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循环总胆红素浓度与非酒精性脂肪肝和全因死亡率风险的非线性关联

越来越多的证据表明，总胆红素轻度升高在多种代谢疾病中具有抗氧化和抗炎特性。我们的目的是探讨循环总胆红素浓度与非酒精性脂肪肝疾病 (NAFLD) 风险和全因死亡率的关系，并检查它们之间潜在的非线性关系。我们使用了来自国家健康和营养检查调查 (NHANES) 的全国代表性数据。 NAFLD 分别使用脂肪肝指数 (FLI) 和美国脂肪肝指数 (USFLI) 进行评估。 FLI-NAFLD（NAFLD 病例由 FLI 诊断）和 USFLI-NAFLD（NAFLD 病例由 USFLI 诊断）组分别包括 35 912 名和 17 329 名参与者。总人口平均年龄46.25岁，其中男性占48.51%。与总胆红素浓度最低五分位数的参与者相比，五分位数最高的参与者在 FLI-NAFLD（OR：0.48，95% CI：0.40，0.59）和 USFLI-NAFLD（OR：0.55，95% CI）中发生 NAFLD 的风险较低：0.43，0.70）组。与总胆红素浓度最低五分位数的参与者相比，总胆红素浓度最高五分位数的参与者中总胆红素浓度与全因死亡率之间的相关性并不显着（HR：0.89，95％CI：0.66，1.20）。受限样条曲线显示总胆红素浓度与 NAFLD 风险和全因死亡率呈非线性 U 形关联。分段线性回归分析显示，FLI-NAFLD（OR：0.94，95% CI：0.93，0.95）和 USFLI-NAFLD（OR：0.95，95% CI：0.93，0.96）中总胆红素浓度与 NAFLD 风险呈负相关。 ）当总胆红素浓度低于转折点时（FLI-NAFLD：18.81 μmol/L；USFLI-NAFLD：15.39 μmol/L）组，当总胆红素浓度高于转折点时，这些关联不显着。此外，随着总胆红素浓度增加到转折点（11.97 μmol/L），全因死亡率下降（OR：0.97，95％CI：0.95，1.00），然后随着总胆红素浓度增加，全因死亡率增加（或：1.03，95%CI：1.02，1.04）。我们发现，生理范围内较高的循环总胆红素浓度与 NAFLD 患者的 NAFLD 风险和全因死亡率降低相关。