956 Kasr Alainy Fibrosis Index (KAFI) - A Novel Score Based on Micro RNAs for Diagnosis of Significant Fibrosis: A Biopsy Controlled Study

Abstract

INTRODUCTION: Precise identification of HCV induced liver fibrosis is needed for tailoring therapy, monitoring fibrosis regression after sustained virologic response and management of complications. Few studies investigated the role of MicroRNAs in predicting liver fibrosis. The current study evaluated the diagnostic accuracy of circulating miRNAs; miR-122, miR-192, miR-855, miR-375, miR-224, and miR-221 in prediction of hepatic fibrosis and to validate their usefulness against other commonly used noninvasive fibrosis scores using liver biopsy as the gold standard. METHODS: Seventy patients with chronic HCV, enrolled from Theodor Bilhariz research institute were included in this study. They were subjected to routine laboratory investigations, HCV-RNA, serum miR-122, 192, 885, 375, 224 and 221 by PCR, ultrasound guided liver biopsy and calculation of the following scores: Fibrosis Index (Fi), Fibro-Alfa , Hui index , aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), Biotechnology Research Center (BRC) score, aspartate to platelet ratio index (APRI), Fibro-Q , Gotebörg University Cirrhosis Index) (GUCI) and FIB-4 score. RESULTS: There was no statistically significant difference in laboratory parameters except for miR-122 which was significantly lower in patients with significant and advanced fibrosis (P < 0.0001 and P = 0.007, respectively). Univariate analysis identified miR-122, bilirubin and miR-855 as independent predictors of significant fibrosis. The AUC were 0.78, 0.67and 0.63, respectively (Figure 1a,c). Multivariate analysis selected the best overall formula combining miR-122, bilirubin and miR-855 as a novel noninvasive score for predicting significant liver fibrosis. KAFI Score = 4.558 – (miR-122 × 0.089 + miR-855 × 0.051 + bilirubin × 0.366), where 4.558 is a numeric constant. The area under the ROC curve (AUC) of this score for identifying significant fibrosis was 0.83 (Figure 1d). A cut-off of 0.41 had 77% sensitivity, 75% specificity, 65% positive predictive value, 85 % negative predictive value and 76% efficiency for predicting significant liver fibrosis. The AUCs of FI, Fibro- Alfa, Hui, AAR, BRC, APRI, Fibro-Q, GUCI and FIB 4 were 0.46, 0.53, 0.54, 0.60, 0.61, 0.62, 0.62, 0.62 and 0.67; respectively for predicting significant fibrosis. KAFI score yielded AUC 0.83 for predicting significant fibrosis and 0.80 for predicting advanced fibrosis. CONCLUSION: KAFI score is better than the current scores in discriminating hepatic-fibrosis in chronic hepatitis C patients