The Fibrosis-4 Index Predicts Ceftriaxone-Associated Gallstone Formation: Risk Stratification Using the Fibrosis-4 Index in a Clinical Cohort.

BACKGROUND

Ceftriaxone is widely used because of its broad antimicrobial spectrum and convenient dosing; however, high biliary excretion can lead to calcium-ceftriaxone precipitation and gallstone-like formations. Although exposure-related risk factors have been described, the effect of hepatic fibrosis on ceftriaxone-associated gallstone formations remains unclear.

AIMS: To clarify the role of hepatic fibrosis in ceftriaxone-related gallstone formation.

METHODS

We conducted a retrospective study on adult patients who received intravenous ceftriaxone and underwent abdominal computed tomography at a tertiary hospital between October 2021 and July 2025. The primary outcome was newly detected gallstone formations during or after ceftriaxone therapy. Clinical variables, including treatment duration, cumulative dose, and fibrosis-4 index, were analyzed. Decision tree, Kaplan-Meier, Cox proportional hazards, and receiver operating characteristic analyses were performed.

RESULTS

Among the 320 eligible patients, 98 (30.6%) developed newly detected gallstones. Patients with gallstones had longer treatment duration (10 vs. 6 days, p < 0.001), higher cumulative dose (22 vs. 10 g, p < 0.001), and higher fibrosis-4 scores (2.86 vs. 1.68, p < 0.001). Decision tree analysis identified fibrosis-4 (cutoff: 2.56) as the primary stratifying variable modifying exposure-related thresholds. Kaplan-Meier analysis showed earlier gallstone development in patients with fibrosis-4 ≥ 2.56. In multivariable Cox analysis, fibrosis-4 ≥ 2.56 was independently associated with gallstone formation. The incorporation of fibrosis-4 improved model discrimination.

CONCLUSIONS

Elevated FIB-4 levels were independently associated with CRO-related gallstone formation. The FIB-4 index may facilitate risk stratification during CRO therapy, although the observed association should not be interpreted as direct evidence of hepatic fibrosis.