Publication

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. 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=5,562). 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=1,651). 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 =0.016) 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 =0.04). This association lost its significance (OR 0.94 [95% CI 0.73‐1.21], P =0.65) 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 sex (P <0.02), hypertension (P <0.001) and hypercholesterolemia (P <0.003). 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 <0.001).

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
Number of pages12
JournalLiver International
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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