The term non-alcoholic fatty liver disease (NAFLD) has been replaced by metabolic dysfunction-associated steatotic liver disease (MASLD) which provides an accurate reflection of its strong association with metabolic disorders such as hypertension, type 2 diabetes mellitus, obesity, and dyslipidemia. ^{1, 2} This nomenclature change, endorsed by major liver associations, aims to eliminate stigmatizing language and emphasize metabolic dysfunction as a core driver of this condition. ³ The MASLD includes a range from uncomplicated steatosis to metabolic dysfunction-associated steatohepatitis (MASH) that, in certain cases may advance to cirrhosis and hepatocellular carcinoma (HCC). ^{4, 5, 6}

The final product of purine metabolism, uric acid, is widely known as a potential contributor to MASLD etiologies. Chang, et al. conducted research indicating a robust positive correlation between serum uric acid levels and the likelihood of developing MASLD in a Chinese adult demographic. ⁷ In addition to its involvement in disease initiation, uric acid also had correlations with the severity of liver fibrosis. Experimental investigations indicate that uric acid can exacerbate liver fibrosis by increasing the quantity of hepatic stellate cells (HSCs), upregulating inflammatory mediators, and enhancing collagen I expression. ^{8, 9} Clinical studies, such as that by Yen et al., have reinforced this by showing a significant link between hyperuricemia and liver fibrosis in MALSD/NAFLD patients, suggesting that uric acid may exacerbate inflammation and accelerate HSC activation, particularly in the presence of other metabolic components. ¹⁰

Due to its straightforward measurement and affordability, serum uric acid may act as an important biomarker for risk stratification in MASLD. The present study aimed to determine the correlation between blood uric acid concentrations and the liver fibrosis extent in MASLD patients, with the goal of contributing to a simple, non-invasive strategy for identifying those at higher risk of disease progression.

This study was designed to examine the association between serum uric acid levels and the presence of liver fibrosis among MASLD patients. The findings indicated a statistically significant association, whereby patients with hyperuricemia exhibited approximately a twofold increased risk of significant liver fibrosis (F2–F4) compared with normal serum uric acid patients. This finding reinforces the growing body of evidence that uric acid is more than just a byproduct of metabolism but an active participant in the pathophysiology of MASLD progression. ^{19, 20, 21, 22}

The prevalence of significant fibrosis (43.8%) and hyperuricemia (50.8%) in our study population was substantial, reflecting the heavy burden of metabolic comorbidities. ²³ The high rates of obesity (71.9%) and dyslipidemia (57.8%) in our sample are consistent with the known metabolic underpinnings of MASLD and serve as a predisposing background for both hyperuricemia and liver injury. ^{21, 22, 24}

Our findings align with several large-scale epidemiological and experimental studies. The research by Liu et al., involving nearly 500,000 participants from the UK Biobank, found that gout patients had significantly higher MASLD risks. ²² They proposed a mechanistic model in which hyperuricemia contributes to gut dysbiosis, thereby increasing the permeability of the intestine, which will facilitate the endotoxins’ translocation to the liver. This initiates an inflammatory cascade through the NLRP3 inflammasome in Kupffer cells, triggering the release of pro-inflammatory cytokines (TNF-α and IL-1β), which then activate hepatic stellate cells (HSCs) and facilitate fibrogenesis. ²² This mechanistic pathway provides a strong biological basis for the statistical association observed in our study.

Further experimental evidence from Sari et al. in a mouse model showed that uric acid administration directly increased liver enzymes, inflammatory mediators (TLR4, MCP-1, CD68), HSC proliferation, and collagen I expression, all hallmarks of fibrosis. Crucially, the administration of allopurinol, a xanthine oxidase inhibitor, reversed these effects, underscoring the causal role of uric acid in this process. ²⁵ The national-level data from the NHANES study by Duan et al. also supports our results, showing that higher serum uric acid levels were associated with both liver fibrosis and steatosis, as measured by VCTE, after adjusting for multiple confounders. ^{26, 27} Research conducted on Asian populations, including a study by Lee et al. utilizing Korean NHANES data, substantiates this association, indicating that hyperuricemia correlates with heightened liver enzyme levels and an augmented risk of advanced fibrosis NAFLD patients. ²⁸

The estimated odds ratio of 2.04 observed in this study is clinically significant. This finding indicates that serum uric acid measurement, as a cost-effective and practical test, also has the potential to be a practical initial examination for liver fibrosis risk stratification in patients with MASLD. Those found to be hyperuricemic could be prioritized for further, more definitive non-invasive fibrosis assessments like transient elastography, enabling earlier detection and intervention.

However, it is crucial to acknowledge what the literature is debating. Studies have found that the association of serum uric acid levels with liver fibrosis attenuates or becomes non-significant after comprehensive adjustment for metabolic confounders, such as BMI and insulin resistance. ^{29, 30} This has led some researchers to suggest that hyperuricemia is merely a marker of underlying metabolic syndrome rather than an independent risk factor for fibrosis. While our study did not perform multivariate analysis to control for these factors, the consistency of our bivariate findings with studies that have performed such adjustments lends credence to the hypothesis of an independent role, or at the very least, a significant contributory one within the metabolic milieu.

This study found a significant positive association between elevated serum uric acid levels (hyperuricemia) and advanced liver fibrosis in patients with MASLD. The risk of significant liver fibrosis was two-fold higher among hyperuricemic patients than those who had normal uric acid levels. These findings highlighted that serum uric acid may represent a cost-effective, practical, and accessible biomarker for preliminary risk stratification in MASLD, facilitating the identification of patients who may require further fibrosis assessment. Future prospective cohort studies incorporating long-term follow-up and multivariate analyses are warranted to clarify the independent contribution of uric acid to fibrosis progression and to explore the potency of uric acid-lowering interventions to prevent or delay liver disease progression in this high-risk population.

The Research Ethics Committee of the Faculty of Medicine, Hasanuddin University, granted approval for this study, as evidenced by the ethical approval letter number No. 148/UN4.6.4.5.31/PP36/2025, dated January 27th 2025.

The data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).