Impact of bilirubin molecular species on mortality in patients with acute on chronic liver failure (ACLF).

Introduction and Objectives

Acute-on-chronic liver failure (ACLF) represents a serious and potentially life-threatening complication in patients with chronic liver disease. This condition is characterized by a rapid deterioration of liver function in patients with pre-existing chronic liver disease. Among the numerous biomarkers used to assess the severity and prognosis of ACLF, serum bilirubin has emerged as a key indicator of liver dysfunction and clinical deterioration. This study aims to analyze the performance of molecular bilirubin species, such as unconjugated (UCB), monoglucuronide (BMG) and diglucuronide bilirubin (BDG), and their impact on mortality in individuals with ACLF.

Materials and Patients

The study included 45 patients with ACLF of various etiologies. The diagnosis was made using the European Association for the Study of the Liver (EASL-CLIF) consortium definition. Clinical and laboratory data were collected to determine severity and assess mortality during the 90 days following enrollment. Bilirubin was extracted from serum samples to measure UCB, BMG, and BDG by liquid chromatography-mass spectrometry (LC-MS). The quantification of bilirubin was performed by monitoring the mass charge (m/z) ratio.

Results

Of the 45 patients, 40% (n=18) were categorized as ACLF grade 1, 35.5% (n=16) as ACLF grade 2, and 17.7% (n=8) as ACLF grade 3. Regarding the molecular species of bilirubin, it was observed that the values of UCB, BMG, and BDG increased according to the severity of ACLF, specifically those of BMG (p=0.019). Additionally, it was observed that individuals who died had higher levels of BDG (4.49 vs. 1.17), BMG (64.30 vs. 28.57), and UCB (21.92 vs. 16.99) with respect to individuals who remained alive.

Conclusions

In conclusion, our findings reveal an association between BDG, BMG and UCB levels and ACLF severity, suggesting that the suggest that molecular bilirubin species could be useful as prognostic markers in patients with ACLF. However, further studies are required to validate these findings and further explore the role of bilirubin in the prognosis and pathophysiology of ACLF.

Ethical statement: All procedures performed were carried out in accordance with the ethical standards of the Ethics Committee of the Clinica Medica Sur Foundation (protocol code 2021-EXT-552) and with the 1964 Declaration of Helsinki and its subsequent amendments, or other comparable ethical standards.

Declaration of interests: None.

Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.