S1313 Diagnostic Performance of FIB-4, APRI, and NFS to Estimate Liver Fibrosis in Hepatic Sarcoidosis

Abstract

Introduction: Sarcoidosis is a multi-system granulomatous disease that can affect any organ system. Most patients have some degree of hepatic involvement, which can lead to significant liver fibrosis and cirrhosis in some patients. Liver biopsy is the gold standard for assessing the severity of fibrosis but is invasive, associated with risks, and costly. Non-invasive tests (NITs) using easy-to-obtain clinical variables could be used in sarcoidosis to (1) identify patients at low risk of fibrosis who could avoid unnecessary liver biopsies and (2) detect patients at high risk of fibrosis who should avoid methotrexate, a potentially hepatotoxic medication and the most frequently prescribed steroid-sparing agent in sarcoidosis. While NITs have been studied in other chronic liver diseases, they have not yet been validated in hepatic sarcoidosis. Methods: We included patients with biopsy-proven hepatic sarcoidosis diagnosed from 2014-2021. Liver pathology reports were reviewed, and subjects were categorized based on fibrosis stage using the METAVIR scoring system (F0-F4). Labs collected closest to biopsy date within a +/-6-month window were used to calculate three NITs: AST to Platelet Ratio Index (APRI), Fibrosis-4 score (FIB-4), and NAFLD Fibrosis Score (NFS). Area under the receiver operating characteristic (AUROC) curves and logistic regression were used to determine optimal NIT thresholds and their predictive accuracy. Two thresholds were then selected for their ability to rule in advanced fibrosis (F3-F4) and rule out advanced fibrosis (≤F2) with optimized accuracy. The performance of previously validated cut-offs was also examined. Results: The cohort consisted of 45 subjects, including 8 (18%) with advanced fibrosis on liver biopsy. Patients had a median age of 48 years (IQR 40-54), and the cohort overall was 56% female and 69% Black. Median aspartate aminotransferase (AST) was 60 (34-79) U/L, alanine aminotransferase (ALT) was 54 (34-81) U/L, alkaline phosphatase was 177 (97-431) U/L, albumin was 3.9 (3.6-4.2) g/L, and platelet count was 248 (220-280) 10^9/L. The AUROCs for APRI, FIB-4, and NFS were 0.594, 0.728, 0.761. Test characteristics of optimal and validated cut-offs are shown in Table. Conclusion: In this cohort of patients with hepatic sarcoidosis, FIB-4 and NFS were able to discriminate advanced fibrosis with an acceptable level of accuracy. External validation of these cut-offs for identifying fibrosis will be needed. Table 1. - Thresholds and Test Characteristics for Non-Invasive tests for Determining Advanced Fibrosis. A high threshold (optimized for a specificity of ≥85%) and low threshold (optimized for a sensitivity of ≥85%) were selected to stratify patients as high versus low risk of advanced fibrosis with optimal accuracy. Abbreviations: NIT (Non-invasive test); APRI (AST to Platelet Ratio Index); FIB-4 (Fibrosis-4 score); NFS (NAFLD Fibrosis Score). NIT Fibrosis Stage Optimal Thresholds Sensitivity (%) Specificity (%) Validated Thresholds Sensitivity (%) Specificity (%) AUROC APRI F3-F4 ≥1.1789 25 89 ≥1.5 0 92 0.594 ≤ F2 ≤0.3303 88 19 ≤1 38 78 FIB-4 F3-F4 ≥2.3605 38 89 ≥2.67 38 92 0.728 ≤ F2 ≤0.7779 88 19 ≤1.3 75 54 NFS F3-F4 ≥0.928 32 90 ≥0.676 50 92 0.761 ≤ F2 ≤-2.3224 88 35 ≤-1.455 75 43