European Journal of Cardiovascular Medicine

Acute appendicitis is the most common cause of acute abdomen requiring surgical intervention worldwide [1]. Despite advancements in diagnostic techniques, appendicitis remains a challenging condition to diagnose accurately due to its varied presentations and the absence of a definitive diagnostic marker [2]. Delayed diagnosis and treatment can lead to serious complications such as appendiceal perforation, which significantly increases patient morbidity and mortality [3].

Incidence of hyperbilirubinemia varies from 10 – 25% depending on the etiology [16,17].  In case of appendicitis, due to bacterial overload there could be issues with the appropriate functioning of Kupffer cells. This can lead to dysfunction or damage to hepatocytes leading to elevated serum bilirubin [18]. Studies shows that hyperbilirubinemia is higher in appendiceal perforation compared to mild infection, contributing to the fact that hyperbilirubinemia positively correlated with the severity of appendicitis [19]. Total bilirubin was found to have a sensitivity of 88% and above in various studies [20].

Traditionally, the diagnosis of acute appendicitis has relied heavily on clinical assessment, supported by imaging techniques such as ultrasound and computed tomography (CT) scans. However, these imaging modalities have limitations, including variability in sensitivity, dependency on operator expertise, and higher costs [4]. Laboratory tests, particularly those evaluating white blood cell (WBC) count and C-reactive protein (CRP) levels, have also been used, but their specificity is often limited [5].

Recent studies have suggested that hyperbilirubinemia, or elevated serum bilirubin levels, may serve as a useful predictor of appendiceal perforation [6-8]. Hyperbilirubinemia in the context of appendicitis is believed to result from bacterial infection and subsequent endotoxemia, which impair bile excretion and hepatic function [9]. This phenomenon has been observed in various bacterial infections, where endotoxins from pathogens such as Escherichia coli and Bacteroides disrupt normal bile metabolism [10].

Several studies have explored the relationship between elevated serum bilirubin levels and the severity of appendicitis. For instance, Vetri et al. [11] and Goudar et al. [12] have demonstrated that patients with perforated appendicitis exhibit significantly higher serum bilirubin levels compared to those with uncomplicated appendicitis. These findings suggest that hyperbilirubinemia could be a valuable adjunct in the diagnostic process, aiding in the early identification of patients at risk for complications.

This study aims to further investigate the correlation between hyperbilirubinemia and appendiceal perforation in patients with acute appendicitis. By analysing the serum bilirubin levels in a cohort of patients diagnosed with appendicitis, we seek to evaluate the potential of bilirubin as a supplemental diagnostic marker. Our goal is to provide evidence that can enhance the accuracy and timeliness of appendicitis diagnosis, ultimately improving patient outcomes and reducing the incidence of complications.

This prospective observational study was conducted at the Department of General Surgery, SS Institute of Medical Sciences and Research Centre, Davangere, from March 2022 to March 2024. The primary aim was to investigate the relationship between elevated serum bilirubin levels and the likelihood of appendiceal perforation in patients diagnosed with acute appendicitis.

Patients diagnosed with acute appendicitis or appendiceal perforation were included in the study. The inclusion criteria were patients aged 16 years and above with a clinical, radiological, and histopathological diagnosis of acute appendicitis or appendiceal perforation. Exclusion criteria comprised patients with known liver diseases such as hepatitis, cirrhosis, or alcoholic liver disease, those with haemolytic anaemia, and patients with abdominal trauma or other conditions that could affect bilirubin levels.

Demographic data, including age and sex, were recorded. Clinical data on signs and symptoms of appendicitis, such as right lower quadrant pain, nausea, vomiting, fever, and leucocytosis, were documented. Blood samples were collected from all patients upon admission to measure total bilirubin (Tb), direct bilirubin (Db), indirect bilirubin (Ib), haemoglobin (Hb), total leukocyte count (TLC), blood urea, and serum creatinine levels.

All patients underwent either laparoscopic or open appendicectomy based on clinical indications. The excised appendices were sent for histopathological examination to confirm the diagnosis of acute appendicitis or appendiceal perforation.

Statistical analysis

The collected data were analysed using statistical software. Descriptive statistics, including mean, median, standard deviation, minimum, and maximum values, were calculated for the various parameters. Group comparisons were made between patients with elevated and normal bilirubin levels using independent samples t-tests to compare mean bilirubin levels between groups. Contingency tables and chi-square tests were employed to assess the association between elevated bilirubin levels and the diagnosis of appendicitis or appendiceal perforation. A p-value of less than 0.05 was considered statistically significant.

Demographic and Clinical Characteristics

The study included a total of 100 patients diagnosed with acute appendicitis or appendiceal perforation. The mean age of the participants was 45.7 years (SD = 16.2), with ages ranging from 16 to 79 years (Table 1). Of the total participants, 41 were female (41%) and 59 were male (59%) (Table 2).

Table 1. Age distribution among study participants

Table 2. Gender distribution among study participants

Laboratory Parameters

The distribution of various laboratory parameters among the study participants is presented in Table 3. The mean haemoglobin (Hb) level was found to be 12.700 g/dL (SD = 1.553), with values ranging from 8.900 to 15.90 g/dL. The total leukocyte count (TLC) showed a mean of 11141.860 cells/µL (SD = 3448.791), with a minimum count of 5632 cells/µL and a maximum count of 20080 cells/µL. The mean total bilirubin (Tb) level was 0.919 mg/dL (SD = 0.388), with levels ranging from 0.300 mg/dL to 1.90 mg/dL. Indirect bilirubin (Ib) levels had a mean of 0.625 mg/dL (SD = 0.261), while direct bilirubin (Db) levels showed a mean of 0.355 mg/dL (SD = 0.690). The mean blood urea level was 23.679 mg/dL (SD = 13.165), and the mean serum creatinine level was 0.818 mg/dL (SD = 0.365).

Table 3. Distribution of lab parameters among study participants

Distribution of Liver Function Tests Among Study Groups

The liver function test results were compared between patients with and without appendicitis (Table 4). Patients with appendicitis (n = 44) had significantly higher mean total bilirubin (Tb) levels (mean = 1.193 mg/dL, SD = 0.362) compared to those without appendicitis (n = 56, mean = 0.704 mg/dL, SD = 0.247), with a p-value of <0.001. Similarly, patients with appendicitis had higher mean indirect bilirubin (Ib) levels (mean = 0.811 mg/dL, SD = 0.235) compared to those without appendicitis (mean = 0.479 mg/dL, SD = 0.172), with a p-value of <0.001. The mean direct bilirubin (Db) levels were also significantly higher in patients with appendicitis (mean = 0.530 mg/dL, SD = 1.013) compared to those without appendicitis (mean = 0.218 mg/dL, SD = 0.110), with a p-value of 0.024.

Table 4. Distribution of liver function test among the study groups

Bilirubin Levels and Appendicitis Status

The distribution of bilirubin levels among the study participants is summarized in Table 5. Out of the total participants, 30% (n = 30) had elevated bilirubin levels (greater than 1.0 mg/dL), while 70% (n = 70) had normal bilirubin levels (1.0 mg/dL or less). The status of appendicitis among the participants is shown in Table 6. Of the total participants, 44% (n = 44) were diagnosed with appendicitis, while 56% (n = 56) were not.

Table 5. Bilirubin level among the study participants

Table 6. Status of appendicitis among the participants

Association Between Bilirubin Levels and Appendicitis

The association between bilirubin levels and the presence of appendicitis was examined (Table 7). Among the participants with elevated bilirubin levels, 63.6% (n = 28) had appendicitis, while only 3.6% (n = 2) without appendicitis had elevated bilirubin levels. Conversely, among those with normal bilirubin levels, 96.4% (n = 54) did not have appendicitis, and 36.4% (n = 16) with normal bilirubin levels had appendicitis. The chi-square test indicated a significant association between elevated bilirubin levels and the presence of appendicitis (χ² = 42.3, df = 1, p < 0.001).

The chi-square tests showed a strong association between elevated bilirubin levels and the diagnosis of appendicitis (χ² = 42.3, df = 1, p < 0.001). This significant association suggests that elevated bilirubin levels can serve as a reliable marker for diagnosing appendicitis and potentially predicting appendiceal perforation.

Table 7. Association between bilirubin level and appendicitis

The present study aimed to investigate the role of elevated serum bilirubin levels as a predictor for acute appendicitis and appendiceal perforation. Our findings demonstrated a significant association between hyperbilirubinemia and the presence of appendicitis, corroborating the results of several previous studies.

Acute appendicitis remains the most common and urgent surgical condition, where timely and accurate diagnosis is critical to prevent complications such as perforation. Traditional diagnostic methods, including clinical assessment and imaging, have their limitations. Laboratory tests, particularly those evaluating inflammatory markers like white blood cell (WBC) count and C-reactive protein (CRP) levels, are commonly used but often lack specificity. Recent studies have highlighted the potential of hyperbilirubinemia as a more specific marker for diagnosing appendicitis and predicting perforation.

The association between elevated serum bilirubin levels and appendicitis is thought to result from bacterial infection and endotoxemia, which impair bile excretion and hepatic function. Escherichia coli and Bacteroides, common pathogens isolated in appendicitis, produce endotoxins that disrupt normal bile metabolism, leading to hyperbilirubinemia. This pathophysiological mechanism supports the use of bilirubin levels as a diagnostic tool in appendicitis.

Vetri et al. [17] and Goudar et al. [18] found that patients with perforated appendicitis had significantly higher bilirubin levels compared to those with uncomplicated appendicitis. Their studies support our findings that elevated bilirubin levels are strongly associated with appendiceal perforation. Moreover, our study's results align with the work of Bakshi et al. [16], who demonstrated the diagnostic value of hyperbilirubinemia in appendicitis, further validating its use as a predictor for appendiceal perforation.

The clinical implications of these findings are significant. Hyperbilirubinemia can serve as a supplemental diagnostic marker, aiding clinicians in the early identification of patients at risk for appendiceal perforation. This is particularly valuable in settings where access to advanced imaging techniques may be limited. By incorporating serum bilirubin measurements into the diagnostic protocol for suspected appendicitis, healthcare providers can improve diagnostic accuracy and expedite appropriate surgical interventions, thereby reducing morbidity and mortality associated with delayed diagnosis.

Elevated serum bilirubin levels are significantly associated with acute appendicitis and can serve as a reliable marker for predicting appendiceal perforation. Patients with appendicitis exhibited higher bilirubin levels compared to those without the condition, supporting the potential diagnostic value of hyperbilirubinemia.

Incorporating serum bilirubin measurements into the diagnostic workup for suspected appendicitis can enhance early detection and improve the accuracy of identifying patients at risk for perforation. Especially in lower resource settings where advanced imaging techniques are not readily available, allowing for more timely and appropriate surgical interventions, ultimately reducing morbidity and mortality associated with delayed diagnosis.

This study has several limitations, including a relatively small sample size and being conducted at a single center, which may limit the generalizability of the findings. Additionally, the study did not include detailed imaging data such as ultrasound or CT scan results, and other inflammatory markers like CRP and WBC count were not analyzed. These factors suggest that further research with larger, multi-center studies and a multi-marker approach is needed to validate and enhance the diagnostic accuracy of serum bilirubin levels in acute appendicitis and appendiceal perforation.

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