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

Turtushikh Damba; Arno R. Bourgonje; Amaal E. Abdulle; Andreas Pasch; Svenja Sydor; Eline H. van den Berg; Ron T. Gansevoort; Stephan J. L. Bakker; Hans Blokzijl; Robin P. F. Dullaart; Harry van Goor; Han Moshage

doi:10.1111/liv.14562

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

Turtushikh Damba, Arno R. Bourgonje, Amaal E. Abdulle, Andreas Pasch, Svenja Sydor, Eline H. van den Berg, Ron T. Gansevoort, Stephan J. L. Bakker, Hans Blokzijl, Robin P. F. Dullaart, Harry van Goor, Han Moshage^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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 language	English
Pages (from-to)	2148-2159
Number of pages	12
Journal	Liver International
Volume	40
Issue number	9
DOIs	https://doi.org/10.1111/liv.14562
Publication status	Published - 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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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. (2020). Oxidative stress is associated with suspected non-alcoholic fatty liver disease and all-cause mortality in the general population. Liver International, 40(9), 2148-2159. https://doi.org/10.1111/liv.14562

@article{fbde2b50a2ac4c799fc0f1907e37bc2a,

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

abstract = "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.",

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

author = "Turtushikh Damba and Bourgonje, {Arno R.} and Abdulle, {Amaal E.} and Andreas Pasch and Svenja Sydor and {van den Berg}, {Eline H.} and Gansevoort, {Ron T.} and Bakker, {Stephan J. L.} and Hans Blokzijl and Dullaart, {Robin P. F.} and {van Goor}, Harry and Han Moshage",

year = "2020",

month = jun,

day = "28",

doi = "10.1111/liv.14562",

language = "English",

volume = "40",

pages = "2148--2159",

journal = "Liver International",

issn = "1478-3231",

publisher = "Wiley",

number = "9",

}

Damba, T, Bourgonje, AR , Abdulle, AE, Pasch, A, Sydor, S, van den Berg, EH, Gansevoort, RT , Bakker, SJL , Blokzijl, H , Dullaart, RPF , van Goor, H & Moshage, H 2020, 'Oxidative stress is associated with suspected non-alcoholic fatty liver disease and all-cause mortality in the general population', Liver International, vol. 40, no. 9, pp. 2148-2159. https://doi.org/10.1111/liv.14562

TY - JOUR

T1 - Oxidative stress is associated with suspected non-alcoholic fatty liver disease and all-cause mortality in the general population

AU - Damba, Turtushikh

AU - Bourgonje, Arno R.

AU - Abdulle, Amaal E.

AU - Pasch, Andreas

AU - Sydor, Svenja

AU - van den Berg, Eline H.

AU - Gansevoort, Ron T.

AU - Bakker, Stephan J. L.

AU - Blokzijl, Hans

AU - Dullaart, Robin P. F.

AU - van Goor, Harry

AU - Moshage, Han

PY - 2020/6/28

Y1 - 2020/6/28

N2 - 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.

AB - 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.

KW - fatty liver index FLI

KW - free thiols

KW - NAFLD

KW - oxidative stress

KW - DENSITY-LIPOPROTEIN CHOLESTEROL

KW - HYDROGEN-SULFIDE

KW - RISK-FACTORS

KW - HOMEOSTASIS

KW - ALBUMIN

KW - MARKERS

KW - PLASMA

KW - THIOLS

U2 - 10.1111/liv.14562

DO - 10.1111/liv.14562

M3 - Article

SN - 1478-3231

VL - 40

SP - 2148

EP - 2159

JO - Liver International

JF - Liver International

IS - 9

ER -

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

Abstract

Keywords

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