# Hyperbilirubinemia as a Marker for Complicated Acute Appendicitis: A Systematic Review

**Authors:** Alicja Czyszczon, Bartosz Maczkowski, Aneta Tkaczyk, Marek Drozdz, Wiktoria Boral, Szymon Mikler, Magdalena Mandyna, Aleksandra Przelaskowska, Jan Pulinski

PMC · DOI: 10.7759/cureus.93197 · 2025-09-25

## TL;DR

High bilirubin levels may indicate severe appendicitis, helping doctors identify dangerous cases when combined with other tests.

## Contribution

This review shows hyperbilirubinemia is a specific marker for complicated appendicitis, especially perforation.

## Key findings

- Hyperbilirubinemia is associated with perforated appendicitis.
- Bilirubin has higher specificity than traditional markers like CRP or leukocytosis.
- Bilirubin should be used alongside clinical and imaging data, not alone.

## Abstract

Acute appendicitis (AA) is one of the most common causes of acute abdomen requiring urgent surgical intervention, and early recognition of complicated forms, such as perforation or gangrene, is crucial to reducing mortality and complications. In recent years, bilirubin has gained attention as a potential biomarker of disease severity. The aim of this systematic literature review was to evaluate the diagnostic usefulness of total bilirubin concentration as a marker of complications in AA, with particular emphasis on perforation, and to analyze its effectiveness in differentiating uncomplicated and complicated forms. A systematic search of PubMed, ScienceDirect, and Google Scholar was performed to identify studies exploring the relationship between bilirubin levels and the severity of AA. The literature indicates a correlation between hyperbilirubinemia and perforated appendicitis. Bilirubin has higher diagnostic specificity compared to classical inflammatory markers such as leukocytosis or C-reactive protein (CRP), especially when combined with clinical assessment and imaging studies. Both retrospective and prospective studies suggest that elevated bilirubin significantly increases the risk of complicated disease. Based on the evidence synthesized in this review, hyperbilirubinemia appears to be associated with complicated forms of AA, particularly perforation. While it demonstrates higher specificity than classical inflammatory markers, the available studies emphasize that it should not be used as a stand-alone diagnostic marker. Instead, bilirubin may be considered a supportive parameter, particularly when interpreted together with clinical evaluation and imaging findings.

## Linked entities

- **Chemicals:** bilirubin (PubChem CID 5280352)
- **Diseases:** acute appendicitis (MONDO:0005649)

## Full-text entities

- **Genes:** CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}
- **Diseases:** inflammatory (MESH:D007249), AA (MESH:D001064), acute abdomen (MESH:D000006), Hyperbilirubinemia (MESH:D006932), perforation (MESH:D057112), gangrene (MESH:D005734), leukocytosis (MESH:D007964)
- **Chemicals:** Bilirubin (MESH:D001663)

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12553480/full.md

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Source: https://tomesphere.com/paper/PMC12553480