Subclinical Liver Fibrosis and Associated Risk Factors and Clinical Outcomes in CKD: The CRIC Study

Background: Metabolic abnormalities associated with CKD may lead to liver fibrosis. We studied the incidence, risk factors, ASCVD, and mortality associated with subclinical liver fibrosis in CKD patients. Methods: This analysis included 3,485 CKD patients from the Chronic Renal Insufficiency Cohort (CRIC) Study, excluding those with missing values. The mean follow-up was 8.2 years. The validated FIB-4 index (age × AST / (PLT × √ALT) evaluated subclinical liver fibrosis (defined as a FIB-4 >3.25). CVD and death events were adjudicated by two physicians. Cox proportional hazards models with backward selection examined risk factors for incident liver fibrosis, including CVD risk factors, eGFR, uACR, and biomarkers (inflammation, mineral bone disorder, fibrosis, and NT-proBNP). The models also assessed the link of FIB-4 with ASCVD and all-cause mortality. Results: The average age was 62 for those with FIB-4 > 3.25 and 57 for those with FIB-4 ≤ 3.25. The age-adjusted incidence was 14.0 per 1000 person-years (17.5 for men and 10.1 for women). Multivariable-adjusted hazard ratios (HR) and 95% CI for liver fibrosis and risk factors are shown in Table. HR (95% CI) for one SD higher FIB-4 were 1.06 (1.02, 1.11) for ASCVD and 1.07 (1.03, 1.10) for all-cause mortality, adjusted for confounders including eGFR and uACR. Conclusion: This study indicates that age, male, mineral bone disorder, inflammation, fibrotic factors, and volume overload are independently associated with risk of subclinical liver fibrosis. Additionally, liver fibrosis was associated with ASCVD and all-cause mortality. Further studies are needed to assess liver fibrosis and related interventions in CKD. Funding: NIDDK Support - NIDDK Support, NIDDK Support Significant Multivariable-Adjusted Hazard Ratios of Liver Fibrosis Associated with Risk Factors - Multivariable-adjusted Variables Hazard ratio (95% CI) P-value Age, (per SD, 11 years) 1.97 (1.68, 2.31) <.0001 Male 2.15 (1.64, 2.81) <.0001 Alkaline phosphatase (per 1 SD, 33.91, u/L) 1.14(1.01, 1.28) 0.03 Log (TGF-β) (per 1SD, 0.78 ng/mL) 0.86 (0.77, 0.96) 0.006 Log (hsCRP) (per 1SD, 1.25 mg/L) 0.79 (0.69, 0.90) 0.001 Log (IL-6) (per 1SD, 0.89 pg/mL) 1.16 (1.01, 1.33) 0.04 Galectin-3 (per 1SD, 7.09 ng/mL) 1.27 (1.12, 1.44) 0.0002 Log (NT-proBNP) (per 1SD, 1.41 ng/mL) 1.16 (1.01, 1.34) 0.04