Gout is independently associated with occult hepatic fibro-inflammation independent of obesity: a multi-cohort study...

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).

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.

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.

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.