European Journal of Cardiovascular Medicine

Alcoholic liver disease (ALD) is a significant cause of morbidity and mortality worldwide, with complications such as cirrhosis, hepatic decompensation, and ascites frequently observed in advanced stages [1]. Among these complications, spontaneous bacterial peritonitis (SBP), characterized by an infection of ascitic fluid without an identifiable intra-abdominal source, is a major concern [2]. The presence of ascitic fluid neutrophils is a crucial diagnostic marker for SBP, and a neutrophil count of ≥250 cells/mm³ is considered the threshold for diagnosis [3].

Hyperuricemia is a known consequence of chronic alcohol consumption and liver dysfunction [4]. Serum uric acid (SUA) levels are influenced by hepatic metabolism, renal excretion, and systemic inflammatory responses, all of which are frequently altered in ALD [5]. Increased SUA has been associated with oxidative stress, endothelial dysfunction, and inflammatory activation, which play a role in the progression of liver disease [6]. Given that inflammation is a key mediator in ALD pathogenesis, SUA may serve as a biomarker reflecting systemic and local inflammatory responses, including those in the ascitic fluid [7].

Previous studies have explored the correlation between SUA and various inflammatory markers in liver disease, but limited research exists on its relationship with ascitic fluid neutrophil count [8]. Understanding this correlation may provide insights into the inflammatory dynamics in ALD and its complications, potentially aiding in early risk stratification for SBP and guiding therapeutic interventions [9].

This study aims to evaluate the correlation between ascitic fluid neutrophil count and serum uric acid levels in patients with ALD. By investigating this relationship, we seek to determine whether SUA can serve as a potential marker for ascitic fluid inflammation and bacterial peritonitis in these patients.

This was a prospective observational study conducted in a tertiary care Indian medical center. 80 patients diagnosed with ALD and presenting with ascites were included in the study. The diagnosis of ALD was based on clinical history, laboratory findings, and imaging studies, following the criteria established by the European Association for the Study of the Liver (EASL) [10].

Patients included in the study were adults aged 18 years or older with a confirmed diagnosis of ALD. The presence of ascitic fluid was verified through ultrasound examination. Additionally, participants had not received antibiotic treatment for SBP in the preceding two weeks. Only individuals with complete clinical and laboratory data were considered for inclusion.

Exclusion criteria comprised patients with cirrhosis resulting from etiologies other than alcohol consumption, such as viral hepatitis, autoimmune liver disease, or metabolic liver disorders. Individuals with a history of malignancy, including hepatocellular carcinoma, were excluded. Patients diagnosed with chronic kidney disease, defined by an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m², were also not eligible. Furthermore, those receiving urate-lowering therapy and pregnant or lactating women were excluded from the study.

Demographic and clinical data, including age, sex, history of alcohol consumption, and presence of complications (hepatic encephalopathy, gastrointestinal bleeding), were recorded.

Serum uric acid (SUA) levels were measured using an enzymatic colorimetric method on an automated biochemistry analyzer. The reference range for SUA was considered as 3.4–7.0 mg/dL in males and 2.4–6.0 mg/dL in females [11].

Ascitic fluid was collected via ultrasound-guided paracentesis under aseptic conditions. Ascitic fluid neutrophil count was determined using an automated cell counter. A neutrophil count of ≥250 cells/mm³ was considered indicative of SBP [12]. Protein and albumin levels were measured using colorimetric and bromocresol green methods, respectively. Serum-ascitic albumin gradient (SAAG) was calculated as the difference between serum and ascitic fluid albumin levels.

All statistical analyses were performed using SPSS version 23. Continuous variables were expressed as mean ± standard deviation (SD) or median (interquartile range, IQR), depending on data distribution. Categorical variables were presented as frequencies and percentages. Pearson’s or Spearman’s correlation coefficient was used to assess the relationship between SUA levels and ascitic fluid neutrophil count.

A receiver operating characteristic (ROC) curve analysis was performed to determine the predictive value of SUA for SBP.A p-value <0.05 was considered statistically significant.

A total of 80 patients diagnosed with alcoholic liver disease (ALD) and ascites were included in the study. The mean age of the participants was 52.4 ± 8.6 years, with 86.3% (69/80) being male. The median duration of alcohol consumption was 18 years (IQR: 12–25 years). The clinical characteristics of the study population are summarized in Table 1.

Table 1: Baseline Demographic and Clinical Characteristics of Study Population

The mean serum uric acid (SUA) level in the study cohort was 7.9 ± 2.1 mg/dL, with 58.8% (47/80) of patients exhibiting hyperuricemia (SUA >7.0 mg/dL in males and >6.0 mg/dL in females).** The mean ascitic fluid neutrophil count was 295.6 ± 145.3 cells/mm³.A comparison of biochemical parameters between patients with and without spontaneous bacterial peritonitis (SBP) is shown in Table 2.

Table 2: Comparison of Biochemical Parameters between SBP and Non-SBP Groups

A statistically significant positive correlation was observed between SUA levels and ascitic fluid neutrophil count (r = 0.62, p < 0.001), indicating that patients with higher SUA levels also had increased neutrophil counts in ascitic fluid.To further examine this relationship, patients were divided into two groups based on the SUA cutoff of 8.1 mg/dL, as determined by receiver operating characteristic (ROC) curve analysis. The comparison between these groups is presented in Table 3.

Table 3: Comparison of Ascitic Fluid Neutrophil Count Based on SUA Levels

Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of SUA for SBP. The analysis revealed that SUA had a good predictive value, with an area under the curve (AUC) of 0.81 (95% CI: 0.73–0.89, p < 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of SUA at different cutoff values are summarized in Table 4.

Figure 1: Correlation between Serum Uric Acid and Ascitic Fluid Neutrophil Count

Figure 2: ROC Curve for SUA in Predicting Spontaneous Bacterial Peritonitis (SBP)

This study aimed to evaluate the correlation between serum uric acid (SUA) levels and ascitic fluid neutrophil count in patients with alcoholic liver disease (ALD) and ascites. The results demonstrated a significant positive correlation (r = 0.62, p < 0.001), suggesting that elevated SUA levels may be associated with increased inflammatory activity in ascitic fluid. Furthermore, SUA levels were significantly higher in patients with spontaneous bacterial peritonitis (SBP) compared to those without SBP (8.7 ± 2.3 mg/dL vs. 7.3 ± 1.8 mg/dL, p = 0.003).

Uric acid, a product of purine metabolism, is increasingly recognized as a marker of systemic inflammation and oxidative stress. Hyperuricemia has been associated with the activation of inflammatory pathways, including the NLRP3 inflammasome, which contributes to immune cell activation and cytokine release [13]. In the context of liver disease, SUA levels may reflect the degree of hepatic dysfunction and systemic inflammatory response [14]. Previous studies have suggested that uric acid plays a role in the pathophysiology of cirrhosis-related complications, including renal dysfunction, systemic inflammation, and cardiovascular risk [15]. In patients with decompensated cirrhosis, elevated SUA levels have been linked to worsening hepatic synthetic function and increased mortality risk [16]. Our findings further support the role of SUA as a non-invasive biomarker that correlates with intra-abdominal infection in ALD-related ascites.

SBP is a serious complication in cirrhotic patients with ascites, characterized by bacterial translocation and an exaggerated inflammatory response [10]. The significant association between SUA levels and SBP in our study highlights a potential role for SUA in predicting bacterial peritonitis. In our analysis, SUA ≥8.1 mg/dL was associated with significantly higher ascitic fluid neutrophil counts (398.3 ± 132.5 cells/mm³ vs. 205.6 ± 98.2 cells/mm³, p < 0.001). Additionally, ROC curve analysis demonstrated that SUA had a good predictive value for SBP (AUC = 0.81, 95% CI: 0.73–0.89, p < 0.001), with a sensitivity of 76.5% and specificity of 82.6%. This is in line with prior research indicating that hyperuricemia is associated with bacterial infections in cirrhosis. A study by Lee et al. [17] found that SUA levels were significantly higher in cirrhotic patients with infection-related complications, suggesting that uric acid may serve as an adjunct marker for infection risk assessment. Similarly, another study reported that elevated SUA levels were predictive of sepsis and worse outcomes in critically ill patients with liver disease [18].

The potential mechanisms linking serum uric acid (SUA) and systolic blood pressure (SBP) are likely multifactorial. One key pathway involves oxidative stress and inflammation, as uric acid is known to promote oxidative damage, resulting in endothelial dysfunction and increased vascular permeability, which may facilitate bacterial translocation from the gut [19]. Additionally, hepatic dysfunction plays a crucial role in uric acid metabolism, and impaired liver function in cirrhotic patients may contribute to elevated SUA levels due to reduced clearance [20]. Furthermore, renal dysfunction is another contributing factor, as many patients with cirrhosis develop hepatorenal syndrome, leading to impaired uric acid excretion and subsequent accumulation in the bloodstream [20].

The identification of serum uric acid (SUA) as a potential biomarker for spontaneous bacterial peritonitis (SBP) carries significant clinical implications. SUA, being a readily measurable and cost-effective parameter, could serve as a non-invasive tool for risk stratification in cirrhotic patients, enabling early identification of those at higher risk of SBP. Moreover, patients with elevated SUA levels could be prioritized for early diagnostic paracentesis and empirical antibiotic therapy, potentially improving clinical outcomes. Additionally, individuals with persistently high SUA levels may benefit from prophylactic antibiotic strategies aimed at preventing SBP episodes.

However, this study has several limitations. As a single-center study conducted in a tertiary care hospital with limited resources, the findings may not be generalizable to broader populations. Furthermore, the observational design precludes establishing a causal relationship between SUA and SBP, despite the strong correlation observed. Another limitation is the lack of longitudinal follow-up, preventing assessment of whether SUA levels fluctuate with disease progression or response to treatment. Future research should explore SUA dynamics over time to better understand its role in disease monitoring.

To further substantiate these findings, multi-center prospective studies are required to validate the predictive utility of SUA in SBP diagnosis. Additionally, investigations should assess whether interventions targeting SUA levels, such as urate-lowering therapies, influence infection risk or clinical outcomes in cirrhotic patients. Future studies should also examine the mechanistic pathways linking SUA with gut microbiota alterations and systemic inflammation in liver disease to provide deeper insights into the pathophysiological role of uric acid in cirrhosis-related infections.

This study demonstrated a significant correlation between serum uric acid levels and ascitic fluid neutrophil count in alcoholic liver disease. Patients with spontaneous bacterial peritonitis had significantly higher SUA levels, and SUA ≥8.1 mg/dL emerged as a promising non-invasive marker for SBP prediction. Given its clinical utility and ease of measurement, SUA may serve as an adjunctive biomarker for early risk stratification and diagnosis of SBP in patients with ALD-related ascites.

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