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Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents

  • Author Footnotes
    † These authors have contributed equally as joint first authors.
    Antonella Mosca
    Footnotes
    † These authors have contributed equally as joint first authors.
    Affiliations
    Hepatometabolic Unit – Bambino Gesù Children’s Hospital, Rome, Italy
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  • Author Footnotes
    † These authors have contributed equally as joint first authors.
    Valerio Nobili
    Correspondence
    Corresponding author. Address: HepatoMetabolic Unit “Bambino Gesù” Children’s Hospital, Rome 00165, Italy. Fax: +39 06 68593889.
    Footnotes
    † These authors have contributed equally as joint first authors.
    Affiliations
    Hepatometabolic Unit – Bambino Gesù Children’s Hospital, Rome, Italy

    Histopathology Unit, Bambino Gesù Hospital, IRCCS, Rome, Italy
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  • Rita De Vito
    Affiliations
    Histopathology Unit, Bambino Gesù Hospital, IRCCS, Rome, Italy
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  • Annalisa Crudele
    Affiliations
    Liver Research Unit – Bambino Gesù Children’s Hospital, Rome, Italy
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  • Eleonora Scorletti
    Affiliations
    Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom

    NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, United Kingdom
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  • Alberto Villani
    Affiliations
    Paediatrics and Infectious Disease, Bambino Gesù Children Hospital, IRCCS, Rome, Italy
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  • Anna Alisi
    Affiliations
    Liver Research Unit – Bambino Gesù Children’s Hospital, Rome, Italy
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  • Christopher D. Byrne
    Affiliations
    Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom

    NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, United Kingdom
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  • Author Footnotes
    † These authors have contributed equally as joint first authors.
Published:February 14, 2017DOI:https://doi.org/10.1016/j.jhep.2016.12.025

      Background & Aims

      Recent research has suggested that dietary fructose intake may increase serum uric acid (UA) concentrations. Both UA concentration and fructose consumption maybe also increase in NAFLD. It is not known whether dietary fructose consumption and UA concentration are independently associated with non-alcoholic steatohepatitis (NASH). Our aim was to investigate the factors associated with NASH in children and adolescents with proven NAFLD, and to test whether UA concentrations and fructose consumption are independently associated with NASH.

      Methods

      Obese children with NAFLD were studied (n = 271). NASH was diagnosed by a NAFLD activity score ⩾5 and the fatty liver inhibition of progression (FLIP) algorithm. Fructose consumption (g/day) was assessed by food frequency questionnaire, and UA (mg/dl) was measured in serum. Binary logistic regression with adjustment for covariates and potential confounders was undertaken to test factors independently associated with NASH.

      Results

      NASH occurred in 37.6% of patients. Hyperuricaemia (UA ⩾5.9 mg/dl) was present in 47% of patients with NASH compared with 29.7% of non-NASH patients (p = 0.003). Both UA concentration (OR = 2.488, 95% CI: 1.87–2.83, p = 0.004) and fructose consumption (OR = 1.612, 95% CI 1.25–1.86, p = 0.001) were independently associated with NASH, after adjustment for multiple (and all) measured confounders. Fructose consumption was independently associated with hyperuricaemia (OR = 2.021, 95% CI: 1.66–2.78, p = 0.01). These data were confirmed using the FLIP algorithm.

      Conclusions

      Both dietary fructose consumption and serum UA concentrations are independently associated with NASH. Fructose consumption was the only factor independently associated with serum UA concentration.

      Lay summary

      Currently, it is not known whether dietary fructose consumption and uric acid (UA) concentration are linked with non-alcoholic steatohepatitis (NASH) in children and adolescents. Our aim was to test whether UA concentrations and fructose consumption are independently associated with NASH in children and adolescents with proven non-alcoholic fatty liver disease (NAFLD). We show that both dietary fructose consumption and serum UA concentrations are independently associated with NASH and fructose consumption was independently linked with high serum UA concentrations.

      Graphical abstract

      Keywords

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      Linked Article

      • Fructose, uric acid, and zonal differences in NASH
        Journal of HepatologyVol. 67Issue 5
        • Preview
          We read with interest the article by Mosca et al. on the association between fructose consumption, uric acid concentration, and paediatric non-alcoholic steatohepatitis (NASH).1 The authors used a well characterised cohort of patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), in whom they measured serum uric acid concentrations and estimated fructose intake using a dietary questionnaire. Fructose intake and uric acid concentrations were higher in patients with definite NASH, which was defined as a NAFLD Activity Score (NAS) of ⩾5 and was confirmed using the FLIP algorithm.
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      • Energy drinks and adolescents – A hepatic health hazard?
        Journal of HepatologyVol. 68Issue 4
        • Preview
          We read with great interest the paper entitled “Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents”, published by Mosca et al. in the Journal of Hepatology, 2017.1
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      • Reply to: “Energy drinks and adolescents – A hepatic health hazard?”
        Journal of HepatologyVol. 68Issue 4
        • Preview
          We read with interest the letter by Robin et al. referring to our paper entitled “Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents”.1,2 In their letter, the authors report the case of a 17-year-old-boy who developed NASH due to his unhealthy lifestyle and his consumption of energy drinks (EDs). Robin et al. also highlight that other components of the diet, such as niacin, xanthine, taurine and B vitamins, could contribute to liver damage.
        • Full-Text
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      • Reply to: “Fructose, uric acid and zonal differences in NASH”
        Journal of HepatologyVol. 67Issue 5
        • Preview
          We read with interest the letter by Mann & Armstrong, referring to our article entitled “Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents”.1,2 The liver has a unique dual blood supply, receiving both arterial blood and blood from the portal vein. This phenomenon and the liver cellular architecture results in hepatocytes being exposed to differential oxygen tensions and varying concentrations of dietary nutrients, according to their position across the liver lobule.
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