O-17 STUDY OF THE ASSOCIATION BETWEEN SERUM LEVELS OF SYSTEMIC INFLAMMATORY MARKERS AND ADVANCED FIBROSIS STAGE IN INFECTED PATIENTS WITH HEPATITIS DELTA VIRUS GENOTYPE 3

Abstract

Introduction and Objectives: HDV-3 is responsible for outbreaks of fulminant hepatitis in northeastern South America. There are no studies investigating immune responses in relation to liver damage caused by HDV-3. This study aimed to investigate if systemic inflammatory molecules (SIM) are differentially expressed in patients with advanced fibrosis chronically infected with HDV genotype 3. Materials and Methods: 61 patients coinfected with HBV/HDV-3 naive were included in this study. Diagnostic tests to screen for HBV/HDV infections were performed using standard immune serology testing. HDV quantification and genotyping was performed by semi-nested RT-PCR and RFLP methodology. 92 SIMs were measured by Proximity Extension Assay (PEA) technology(Proseek Multiplex Inflammation I assay). Shapiro-Wilk, Student's t test, Mann-Whitney tests and logistic regression analysis were used when appropriate. Results: The median age was 41 years(18-59 years) and all patients were HBeAg negative. Advanced fibrosis or cirrhosis(F3/F4) was diagnosed by histological staging in 17 patients, while 44 presented with minimal or no fibrosis. Advanced necroinflammatory activity correlated positively with serum levels of AST and ALT(p=0.024 and 0.020, respectively). Established non-invasive fibrosis scores (APRI, FIB-4 and AST/ALT ratio) revealed low sensitivities and PPVs with AUROC maximum of 0.586. Among the 92 SIMs analyzed, MCP4 (p = 0.032), CCL19(p = 0.024), EN.RAGE(p = 0.014), SCF(p = 0.01) and IL 18(p = 0.054) showed a positive correlation with the fibrosis stage. A combined score including CCL19 and MCP.4 revealed a sensitivity of 81% and an Odds Ratio of 2.202 for advanced fibrosis. Conclusions: Standard non-invasive fibrosis scores showed poor performance in HDV G3 infection. We here suggest that the determination of CCL19 and MCP.4 may be used to identify patients with advanced fibrosis. Moreover, this study gives novel insights into the immunopathogenesis of HDV G3 infection.