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Elevated Uric Acid and Metabolic Dysfunction-Associated Steatotic Liver Disease Progression: Where There's Smoke, is There Fire?

Created on 22 Aug 2026

Authors

Eric E Kelley, Owen M Woodward, Nicholas K H Khoo

Published in

Seminars in liver disease. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

Hyperuricemia and metabolic dysfunction-associated steatotic liver disease share overlapping risk factors, yet the mechanistic contribution of uric acid remains unclear. Generation of uric acid occurs exclusively by xanthine oxidoreductase, a process intrinsically linked to electron transfer and oxidant generation, a relationship that can be viewed through electron accounting. This biochemical coupling makes it difficult to determine whether elevated uric acid drives pathology or reflects broader changes in increased redox/oxidative stress. This review highlights mechanisms of uric acid production, its dual antioxidant and pro-oxidant effects, and regulation of urate transporters. We then discuss how western dietary patterns, adiposity, and insulin resistance reshape uric acid homeostasis and intersect with pathways that promote steatosis, inflammation, and fibrogenesis. In conclusion, by framing uric acid within a liver-centered redox perspective, we consider whether elevated uric acid functions as a biomarker of metabolic stress, a contributor to disease progression, and a potential therapeutic target in metabolic dysfunction-associated steatotic liver disease.

PMID:
42628940
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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