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Background and aims <p>Gout frequently co-occurs with steatotic liver disease, but its direct hepatotoxic effect beyond obesity remains contentious. We aimed to elucidate the independent association between gout and hepatic fibro-inflammation, particularly in subclinical cases with normal alanine aminotransferase (ALT).</p> Methods <p>This multi-cohort study integrated a UK Biobank discovery cohort (N = 21,334) using MRI iron-corrected T1 (cT1) mapping, and a multicenter clinical validation cohort (N = 512) using Transient Elastography (FibroScan) to measure liver stiffness (LSM). Multivariable regression and causal mediation analyses dissected “obesity-dependent” versus “independent” pathways.</p> Results <p>Gout patients exhibited significantly elevated liver fibro-inflammation and steatosis across both cohorts. After full adjustment for metabolic confounders, gout was independently associated with liver injury in the UK Biobank (<i>β-cT1</i> = 6.41&#xa0;ms, <i>p</i> = 0.025) and clinical cohort (<i>β-LSM</i> = 1.21&#xa0;kPa, <i>p</i> &lt; 0.001). This association consistently persisted in non-obese patients with normal ALT (&lt; 40&#xa0;U/L), indicating occult injury. Mediation analysis revealed a “Double Hit” mechanism: 51.3% of the effect was obesity-mediated, while 48.7% was independent of body mass index.</p> Conclusion <p>Gout is an independent factor associated with subclinical hepatic fibro-inflammation, even in non-obese, normo-enzymatic patients. This challenges reliance on ALT screening alone, warranting the integration of sensitive liver health assessments into routine gout management.</p> Graphical abstract <p></p>

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Gout is independently associated with occult hepatic fibro-inflammation independent of obesity: a multi-cohort study using MRI-cT1 and elastography

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月25日

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  • Yixian Mei,
  • Weiqi Cai,
  • Qiming Huang,
  • Qingduo Chen,
  • Yongxu Lin,
  • Yaqing Chen,
  • Chenyu Xin,
  • Cunyu Lu,
  • Zheshu Chen,
  • Xiaoping Chen,
  • Jian Ding,
  • Qiuyuan Liu,
  • Dan Li

摘要

Background and aims

Gout frequently co-occurs with steatotic liver disease, but its direct hepatotoxic effect beyond obesity remains contentious. We aimed to elucidate the independent association between gout and hepatic fibro-inflammation, particularly in subclinical cases with normal alanine aminotransferase (ALT).

Methods

This multi-cohort study integrated a UK Biobank discovery cohort (N = 21,334) using MRI iron-corrected T1 (cT1) mapping, and a multicenter clinical validation cohort (N = 512) using Transient Elastography (FibroScan) to measure liver stiffness (LSM). Multivariable regression and causal mediation analyses dissected “obesity-dependent” versus “independent” pathways.

Results

Gout patients exhibited significantly elevated liver fibro-inflammation and steatosis across both cohorts. After full adjustment for metabolic confounders, gout was independently associated with liver injury in the UK Biobank (β-cT1 = 6.41 ms, p = 0.025) and clinical cohort (β-LSM = 1.21 kPa, p < 0.001). This association consistently persisted in non-obese patients with normal ALT (< 40 U/L), indicating occult injury. Mediation analysis revealed a “Double Hit” mechanism: 51.3% of the effect was obesity-mediated, while 48.7% was independent of body mass index.

Conclusion

Gout is an independent factor associated with subclinical hepatic fibro-inflammation, even in non-obese, normo-enzymatic patients. This challenges reliance on ALT screening alone, warranting the integration of sensitive liver health assessments into routine gout management.

Graphical abstract