Elevated liver fibrosis index FIB-4 is associated with poor clinical outcomes in patients with sepsis, an observational cohort study

Abstract

Background: No study for investigating the association between sub-clinical hepatic fibrosis and the outcomes of sepsis was performed before. Therefore, the purpose is to explore the association of liver fibrosis indexes with the outcomes of septic patients without overt chronic liver disease. Methods: We performed a cohort study using data extracted from the Medical Information Mart for Intensive Care Ⅲ database (v1.4). The patient records of additional external validation were obtained from the First Affiliated Hospital of Wenzhou Medical University. Aspartate aminotransferase-platelet ratio index (APRI), fibrosis-4 (FIB-4) score and non-alcoholic fatty liver disease fibrosis score (NFS) were calculated with previous formulas. The primary outcome was 28-day mortality. The secondary outcomes were 90-day mortality, in-hospital mortality and renal replacement therapy (RRT). We assessed the associations of three indexes with primary and secondary outcomes using logistic regression analysis. Furthermore, we performed multivariable analysis, sensitivity analysis and additional external validation to verify the true strength of the results.Results: In the FIB-4-sepsis cohort (N = 1560), there was a statistically significant stepwise increase from Quartile 1 to Quartile 4 in the risk of 28-day mortality (Quartile 1: reference; Quartile 2: OR = 1.570, P = 0.061, 95%CI = 0.980–2.515; Quartile 3: OR = 2.363, P < 0.001, 95%CI = 1.512–3.692; Quartile 4: OR = 2.933, P < 0.001, 95%CI = 1.895–4.538). Similarly, the increased trends could also be found in all secondary outcomes for the FIB-4-sepsis cohort. However, no significant trends were observed in the APRI-sepsis and NFS-sepsis cohorts. The results of multivariable logistic regression analysis, Kaplan-Meier analysis, Cox regression analysis and additional external validation showed good consistency.Conclusions: FIB-4 index was associated with 28-day mortality, 90-day mortality, in-hospital mortality and RRT in the septic patients without overt chronic liver disease. In other words, the high stage of sub-clinical hepatic fibrosis represented by FIB-4 could reflect the poor outcomes of patients with sepsis.