Keywords
MASLD, Uric Acid, Hyperuricemia, Liver Fibrosis, Transient Elastography
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Amiruddin F, Adnan E, Parewangi AL et al. The Relationship Between Uric Acid Level and Liver Fibrosis in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) [version 1; peer review: awaiting peer review]. F1000Research 2026, 15:574 (https://doi.org/10.12688/f1000research.178751.1)
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Research Article
The Relationship Between Uric Acid Level and Liver Fibrosis in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
[version 1; peer review: awaiting peer review]
PUBLISHED 19 Apr 2026
OPEN PEER REVIEW
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Abstract
Corresponding author:
Fitri Amiruddin
Competing interests:
No competing interests were disclosed.
Grant information:
The author(s) declared that no grants were involved in supporting this work.
Copyright:
© 2026 Amiruddin F et al.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
How to cite: Amiruddin F, Adnan E, Parewangi AL et al. The Relationship Between Uric Acid Level and Liver Fibrosis in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) [version 1; peer review: awaiting peer review]. F1000Research 2026, 15:574 (https://doi.org/10.12688/f1000research.178751.1)
First published: 19 Apr 2026, 15:574 (https://doi.org/10.12688/f1000research.178751.1)
Latest published: 19 Apr 2026, 15:574 (https://doi.org/10.12688/f1000research.178751.1)
Introduction
The term non-alcoholic fatty liver disease (NAFLD) has been replaced by metabolic dysfunction-associated steatotic liver disease (MASLD) which provides an accurate reflection of its strong association with metabolic disorders such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.
Methods
Study design and setting
A cross-sectional study was conducted in Dr. Wahidin Sudirohusodo Hospital and its affiliated teaching hospitals in Makassar, Indonesia, from July to December 2025.
Study population
The study population was all MASLD patients who received medical care at the participating hospitals within the designated study period. Patients were enrolled using a consecutive sampling method. The study population was all MASLD patients who received medical care at the participating hospitals within the designated study period. Patients were enrolled using a consecutive sampling method. Participants were provided with verbal briefings regarding data collecting procedures via transient elastography and laboratory examination. After understanding the sample technique orally, agreement was obtained by completing and signing the informed consent form provided before data collection.
Inclusion and exclusion criteria
The inclusion criteria were: (1) adult patients (> 18 years); (2) the MASLD diagnosis was confirmed based on the imaging (ultrasonography, CT scan, or MRI) and/or clinical criteria in accordance with the most recent guidelines, after excluding other etiologies of liver disease, including significant alcohol intake (<20 g/day and <30 g/day for women and men, respectively); (3) available serum uric acid laboratory data; and (4) had undergone a liver fibrosis assessment via transient elastography (FibroScan). Patients with viral hepatitis, evidence of drug-induced hepatotoxicity, receiving urate-lowering therapy, or other established etiologies of chronic liver disease were excluded from the study population.
Operational definitions
• MASLD: The presence of hepatic steatosis (≥5%) on imaging, along with the presence of at least one of five cardiometabolic risk factors: overweight (Asian populations who had body mass index (BMI) of ≥23 kg/m2 (or waist circumference ≥90/80 cm) diabetes mellitus (fasting plasma glucose ≥100 mg/dL or on drug treatment for type 2 diabetes); hypertension (≥130/85 mmHg or on hypertension pharmacotherapy); fasting triglyceride plasma levels of ≥150 mg/dL or on lipid-lowering treatment; and HDL-cholesterol levels were <40 mg/dL and <50 mg/dL for men and women or on lipid-lowering treatment, respectivelu.1,11,12
• Hyperuricemia: Increased serum uric acid level (>7.0 mg/dL and >6.0 mg/dL in men and women, respectively).13,14,15
• Liver fibrosis: Determined by vibration-controlled transient elastography (VCTE/FibroScan). The liver fibrosis was staged as (using liver stiffness measurement (LSM) in kilopascals (kPa))16,17,18:
Data collection procedures
Demographic data (age, gender) were collected for all subjects. The venous blood samples were collected for the assessment of serum uric acid concentrations. All patients underwent liver fibrosis assessment using transient elastography. All study procedures were conducted after informed consent was obtained after a brief explanation of the study from every participant.
Statistical analysis
Statistical Package for the Social Sciences (SPSS) software was used for data analysis. Categorical variables were expressed as frequencies and corresponding percentages. The Chi-square (χ2) test was applied to determine the association between hyperuricemia as an independent variable and the presence of significant liver fibrosis as a dependent variable. A p-value less than 0.05 was statistically significant. We determine the degree of association by calculating the odds ratio (OR), along with its 95% confidence interval (CI).
Results
1. Baseline demographic and clinical data
A total of 128 patients who were diagnosed with MASLD were included in the present study. The mean of participants’ age was 49.8 ± 12 years, ranging from 25 – 77 years old. Most participants were male (67 patients, 52.3%). Hyperuricemia was present in 65 patients (50.8%). Significant liver fibrosis (F2-F4) was found in 56 patients (43.8%). The baseline characteristics were presented in Table 1.
2. The relationship between serum uric acid levels and liver fibrosis
The analysis showed that among patients with hyperuricemia, 34 out of 65 (52.3%) had significant liver fibrosis. Conversely, 22 of 63 participants who had normal serum uric acid levels (34.9%) had significant liver fibrosis. The Chi-square test demonstrated that serum uric acid levels and the severity of liver fibrosis had a significant association (χ2 = 3.93; p = 0.047), as shown in Table 2.
Table 2. Relationship between uric acid levels and liver fibrosis in MASLD patients.
| Variable | Liver fibrosis | OR (95% CI) | p-value | |
|---|---|---|---|---|
| F0-F1 (n, %) | F2-F4 (n, %) | |||
| Normal uric acid | 41 (65.1) | 22 (34.9) | 2.044 (1.004-4.161) | 0.047 |
| Hyperuricemia | 31 (47.7) | 34 (52.3) | ||
The risk estimation indicated that patients with hyperuricemia had 2.04 times higher odds of having significant liver fibrosis compared to participants who have normal uric acid levels (OR = 2.044; 95% CI: 1.004–4.161).
Discussion
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.
Study limitations
There were some limitations in this study. First, the present study was a cross-sectional study that can only assess an association, not causality. Second, the lack of multivariate analysis limited our ability to adequately adjust for potential confounders, including BMI, diabetes mellitus, and hypertension, which are inherently associated with both serum uric acid levels and liver fibrosis. Third, we used non-invasive assessments that cannot replace liver biopsy, the gold standard for fibrosis staging, although non-invasive assessments were critically practiced.
Conclusion
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.
Ethical consideration
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.
Informed consent
The data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).
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how to cite this article
Amiruddin F, Adnan E, Parewangi AL et al. The Relationship Between Uric Acid Level and Liver Fibrosis in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) [version 1; peer review: awaiting peer review]. F1000Research 2026, 15:574 (https://doi.org/10.12688/f1000research.178751.1)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
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