# Serum biomarkers for predicting Crohn’s disease activity: The role of bilirubin, uric acid, and the C-reactive protein/albumin ratio

**Authors:** Ting Xu, Tingting Yao, Yating Chen, Fan Xu, Chunxia Lu

PMC · DOI: 10.1371/journal.pone.0333855 · PLOS One · 2026-03-04

## TL;DR

The study identifies serum biomarkers like bilirubin and the C-reactive protein/albumin ratio that may help track Crohn’s disease activity without invasive procedures.

## Contribution

The novel contribution is identifying the C-reactive protein/albumin ratio as a strong predictor of Crohn’s disease activity and a potential marker for remission.

## Key findings

- The C-reactive protein/albumin ratio showed the highest accuracy in predicting disease activity (AUC = 0.903).
- Post-treatment increases in bilirubin and decreases in C-reactive protein and its ratio were observed in remission.
- Uric acid showed no significant association with disease activity.

## Abstract

Crohn’s disease is a chronic, progressive inflammatory condition of the gastrointestinal tract that requires long-term assessment of disease activity. There is a growing need for convenient serum biomarkers to reduce the need for invasive endoscopic evaluations. Our study aims to explore the predictive value of serum biomarkers, specifically total bilirubin, uric acid, and the C-reactive protein/albumin ratio, for disease activity in Crohn’s disease.

We conducted a retrospective study at the Second Hospital of Anhui Medical University (China), consisting of 170 patients with Crohn’s disease and 100 healthy controls. Clinical characteristics and laboratory biomarkers were collected and analyzed. Among the patients, 77 active Crohn’s disease patients who had complete follow-up data were included in a longitudinal analysis to assess biomarker dynamics.

Compared to healthy controls, Crohn’s disease patients exhibited lower bilirubin and albumin levels, but higher C-reactive protein and C-reactive protein/albumin ratio, trends that intensified with disease progression. Following therapy, albumin, C-reactive protein and C-reactive protein/albumin ratio changed significantly in both remission and active groups, whereas a significant increase in total bilirubin was exclusive to the remission group. Receiver operating characteristic analysis indicated that C-reactive protein/albumin ratio had the highest discriminatory power for disease activity (area under the curve [AUC]= 0.903), outperforming C-reactive protein alone (AUC = 0.894), albumin (AUC = 0.719) and total bilirubin (AUC = 0.648). Regarding uric acid, no significant associations were identified overall, apart from a single weak correlation in Spearman’s analysis.

Our findings support a potential serological remission hypothesis for Crohn’s disease, characterized by a post-treatment rise in total bilirubin, together with a decrease in C-reactive protein to approximately 5.3 mg/L and the C-reactive protein/albumin ratio to about 0.136. This hypothesis warrants prospective validation.

## Linked entities

- **Proteins:** LOC100189571 (uncharacterized LOC100189571)
- **Chemicals:** bilirubin (PubChem CID 5280352), uric acid (PubChem CID 1175)
- **Diseases:** Crohn’s disease (MONDO:0005011)

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, UOX (urate oxidase (pseudogene)) [NCBI Gene 391051] {aka UOXP, URICASE}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, CDAN1 (codanin 1) [NCBI Gene 146059] {aka CDA1, CDAI, CDAN1A, DLT, PRO1295}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}
- **Diseases:** diarrhea (MESH:D003967), autoimmune diseases (MESH:D001327), renal or hepatic dysfunction (MESH:D008107), inflammation (MESH:D007249), perianal disease (MESH:D000694), malignancy (MESH:D009369), liver dysfunction (MESH:D017093), heart disease (MESH:D006331), bacterial (MESH:D001424), IBD (MESH:D015212), ulcerative colitis (MESH:D003093), tissue injury (MESH:D017695), necrosis (MESH:D009336), malnutrition (MESH:D044342), viral infections (MESH:D014777), erosions (MESH:D014077), ulcers (MESH:D014456), infection (MESH:D007239), protein-losing enteropathy (MESH:D011504), CD (MESH:D003424), upper gastrointestinal disease (MESH:D005767)
- **Chemicals:** infliximab (MESH:D000069285), ustekinumab (MESH:D000069549), 5-ASA (MESH:D019804), azathioprine (MESH:D001379), Bilirubin (MESH:D001663), bromocresol green (MESH:D001961), Uric acid (MESH:D014527), purine (MESH:C030985), prednisone (MESH:D011241), creatinine (MESH:D003404), ROS (MESH:D017382), diazonium salt (-), vedolizumab (MESH:C543529), heme (MESH:D006418), Cr (MESH:D002857)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

43 references — full list in the complete paper: https://tomesphere.com/paper/PMC12959708/full.md

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Source: https://tomesphere.com/paper/PMC12959708