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Oxidative stress is associated with suspected non-alcoholic fatty liver disease and all-cause mortality in the general population

Damba, T., Bourgonje, A. R., Abdulle, A. E., Pasch, A., Sydor, S., van den Berg, E. H., Gansevoort, R. T., Bakker, S. J. L., Blokzijl, H., Dullaart, R. P. F., van Goor, H. & Moshage, H., 28-Jun-2020, In : Liver International. 40, 9, p. 2148-2159 12 p.

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)2148-2159
Number of pages12
JournalLiver International
Volume40
Issue number9
Publication statusPublished - 28-Jun-2020

    Keywords

  • fatty liver index FLI, free thiols, NAFLD, oxidative stress, DENSITY-LIPOPROTEIN CHOLESTEROL, HYDROGEN-SULFIDE, RISK-FACTORS, HOMEOSTASIS, ALBUMIN, MARKERS, PLASMA, THIOLS

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