Oxidative stress is associated with suspected non-alcoholic fatty liver disease and all-cause mortality in the general population
Oxidative stress is associated with suspected non-alcoholic fatty liver disease and all-cause mortality in the general population
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DOI：
10.1111/liv.14562
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发表时间：
2020-06-28
影响因子：
6.7
通讯作者：
Moshage, Han
中科院分区：
文献类型：
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作者：
Damba, Turtushikh;Bourgonje, Arno R.;Moshage, Han
背景与目的非酒精性脂肪性肝病（NAFLD）以脂质过度积聚、炎症和氧化还原平衡失调为特征。我们假设，全身游离巯基水平，作为全身氧化应激的代表，与NAFLD相关。方法在来自预防肾和血管终末期疾病（PREVEND）队列研究（n = 5562）的参与者中测定蛋白质校正的血清游离巯基浓度。疑似NAFLD由脂肪肝指数（FLI >= 60）和肝脂肪变性指数（HSI > 36）定义。结果FLI ≥ 60的受试者（n = 1651）的蛋白质校正血清游离巯基显著降低。在多变量logistic回归分析中，蛋白质校正的血清游离巯基与NAFLD相关（FLI >= 60）（或每浓度加倍：0.78 [95%CI 0.64-0.96]，P = 0.016），即使调整了潜在的混杂因素，包括收缩压、糖尿病、当前吸烟，使用酒精和总胆固醇（OR 0.80 [95% CI 0.65-0.99]，P = .04）。在对高敏C反应蛋白进行额外调整后，这种关联失去了意义（OR 0.94 [95% CI 0.73-1.21]，P = 0.65）。分层分析显示，蛋白质校正的血清游离巯基浓度与性别（P <0.02）、高血压（P <0.001）和高胆固醇血症（P <0.003）的疑似NAFLD之间存在显著差异。在NAFLD受试者（FLI >= 60）中，蛋白质校正的血清游离巯基水平与全因死亡风险显著相关（HR 0.27 [95%CI 0.17-0.45]，P <0.001）。结论蛋白质调整的血清游离巯基水平降低，并与疑似NAFLD受试者的全因死亡率显著相关。游离巯基的定量可能是一种有前途的微创策略，可以改善一般人群中NAFLD的检测和相关的全因死亡风险。
Background & Aims Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation, inflammation and an imbalanced redox homeostasis. We hypothesized that systemic free thiol levels, as a proxy of systemic oxidative stress, are associated with NAFLD. Methods Protein-adjusted serum free thiol concentrations were determined in participants from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort study (n = 5562). Suspected NAFLD was defined by the Fatty Liver Index (FLI >= 60) and Hepatic Steatosis Index (HSI > 36). Results Protein-adjusted serum free thiols were significantly reduced in subjects with FLI >= 60 (n = 1651). In multivariable logistic regression analyses, protein-adjusted serum free thiols were associated with NAFLD (FLI >= 60) (OR per doubling of concentration: 0.78 [95% CI 0.64-0.96],P = .016) even when adjusted for potential confounding factors, including systolic blood pressure, diabetes, current smoking, use of alcohol and total cholesterol (OR 0.80 [95% CI 0.65-0.99],P = .04). This association lost its significance (OR 0.94 [95% CI 0.73-1.21],P = .65) after additional adjustment for high-sensitive C-reactive protein. Stratified analyses showed significantly differential associations of protein-adjusted serum free thiol concentrations with suspected NAFLD for gender (P < .02), hypertension (P < .001) and hypercholesterolemia (P < .003). Longitudinally, protein-adjusted serum free thiols were significantly associated with the risk of all-cause mortality in subjects with NAFLD (FLI >= 60) (HR 0.27 [95% CI 0.17-0.45],P < .001). Conclusion Protein-adjusted serum free thiol levels are reduced and significantly associated with all-cause mortality in subjects with suspected NAFLD. Quantification of free thiols may be a promising, minimally invasive strategy to improve detection of NAFLD and associated risk of all-cause mortality in the general population.