Abstract: OBJECTIVE To investigate the clinical utility of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), Clara cell protein 16 (CC-16) and deoxycholic acid (DCA), either individually or in combination, in early identification of acute cholangitis (AC) complicated with septic lung injury. METHODS From Jan. 2022 to Dec. 2024, a total of 67 hospitalized AC patients and 30 healthy controls were prospectively enrolled from Xuzhou Central Hospital. Subjects were divided into three groups: Group A (AC patients with septic lung injury, n=32), Group B (AC patients without septic lung injury, n=35) and Group C (subjects without acute cholangitis or other infectious diseases, n=30). The relationship between the expression levels of sTREM-1, CC-16 and DCA and the occurrence of septic lung injury and disease severity in patients with AC were monitored and analyzed. Receiver operating characteristic (ROC) curves were employed to evaluate the clinical predictive value of these markers for AC complicated with septic lung injury. RESULTS The serum levels of sTREM-1, CC-16 and DCA increased sequentially in Group C, Group B and Group A (P<0.05). The three markers showed positive correlations with Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores (P<0.05). In patients with septic lung injury, serum levels of sTREM-1, CC-16 and DCA were significantly higher on days 1, 3 and 5 after admission compared to those without septic lung injury (P<0.05). The combined detection of sTREM-1, CC-16 and DCA yielded higher area under the curve (AUC) values on days 1, 3 and 5 than individual markers, outperforming CRP and PCT (P<0.05). The highest AUC (0.984, 95% CI: 0.858-0.986) was observed on day 5. CONCLUSIONS Combined detection of serum sTREM-1, CC-16 and DCA enables early and accurate prediction of AC complicated with septic lung injury, providing a basis for individualized intervention and treatment.