Hyperbilirubinemia as a Predictor of Appendiceal Perforation: A Systematic Review and Diagnostic Test Meta-Analysis

Abstract

Background Misdiagnosis of the severity of acute appendicitis may lead to perforation and can consequently result in increased morbidity and mortality. In this study, the role of hyperbilirubinemia as a predictor of perforation is assessed by performing a meta-analysis of diagnostic accuracy. Methods A systematic search of the literature published over the past 20 years was performed using the EMBASE, PubMed, Cochrane library, and Google Scholar databases. Results Low values of sensitivity, specificity, and diagnostic odds ratio (DOR) were detected: 0.21 (95% confidence interval (CI): 0.13 - 0.30, standard error (SE) = 0.43), 0.27 (95% CI: 0.15 - 0.43, SE = 0.73), and 0.10 (95% CI: 0.3 - 0.28, SE = 0.05), respectively. The positive likelihood ratio (PLR) was low (0.29 (95% CI: 0.27 - 0.91, SE = 0.76)), whereas the negative likelihood ratio (NLR) was high (2.88 (95% CI: 1.66 - 5.14, SE = 0.10)). The hierarchical summary receiver operating characteristic curve was positioned towards the lower right corner, and the area under the curve was 0.19, both indicating a low level of overall accuracy and discrimination. Compared with the PLR, the negative inverse likelihood ratio (1/LR - ) indicated that a positive result has a greater impact on the odds of disease than does a negative result. Conclusions Hyperbilirubinemia alone is not a reliable tool to predict perforation. Future studies should investigate whether the combined predictive values of bilirubin, C-reactive protein (CRP), and white blood cells are a more effective diagnostic tool.

Bilirubin, Interleukin 6 (IL 6) and Lipopolysaccharide �Binding Protein (LBP) � Biomarkers of Sepsis in Appendicular Peritonitis

“…They described the rate of appendicular perforation as being 3 times higher for patients with hyperbilirubinemia compared to normal bilirubin levels. Diagnostic accuracy of hyperbilirubinemia in predicting perforated appendicitis was demostrated by several clinical studie [15][16][17][18][19]. More important, in the present study, hyperbilirubinemia proved to be an important biomarker for intraperitoneal sepsis diagnosis and monitoring.…”

The Diagnostic Differentiation Challenge in Acute Appendicitis: How to Distinguish between Uncomplicated and Complicated Appendicitis in Adults

“…Biomarkers have the potential to provide noninvasive objective criteria without any adverse effects on the patient [ 13 ]. Serum bilirubin has been suggested as a possible marker of perforation, as hyperbilirubinemia commonly occurs in patients with septic conditions [ 14 , 15 ]. Bacteremia can cause endotoxemia leading to impaired excretion of bilirubin from the bile canaliculi [ 15 ].…”

“…However, hyperbilirubinemia alone has a low overall accuracy to diagnose a complicated appendicitis with anticipated perforation. In cases where elevated bilirubin occurs, the patient is more likely to be diagnosed with complicated appendicitis [ 14 ], and normal bilirubin supports the presence of an uncomplicated appendicitis [ 15 ]. More research is needed to evaluate whether measurement of serum bilirubin should be integrated into the diagnostic tools when it comes to appendicitis.…”

High C-Reactive Protein level as a predictor for appendiceal perforation

“…All of these scores have been proven useful in predicting AA, but none of them evaluate the risk of perforation. [5] USG and CT are the most preferred imaging modalities. In a meta-analysis, Al-Khayal et al [12] stated that USG had a sensitivity of 83.7% and specificity of 95.9% in cases suspected to have AA.…”

“…However, these two techniques have a low sensitivity in detecting perforated AA. [5] On the other hand, despite the higher specificity and sensitivity values, the downside of CT is exposure to ionized radiation. In a study by Smith-Bindman et al, [14] it was demonstrated that there was an increase in the rate of cancer associated with CTrelated radiation, particularly among young people.…”