Alanine aminotransferase, HCV RNA levels and pro-inflammatory and pro-fibrogenic cytokines/chemokines during acute hepatitis C virus infection.

Behzad Hajarizadeh,Jordan J Feld,Tanya L Applegate,Elizabeth Keoshkerian,Margaret Hellard,Janaki Amin,Gail V Matthews,Gregory J Dore,Jason Grebely,François Mj Lamoury,Andrew R Lloyd

doi:10.1186/s12985-016-0482-x

Abstract

BackgroundThis study assessed the association of alanine-aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels with pro-inflammatory and pro-fibrogenic cytokines and chemokines during acute HCV infection to provide further insight into the potential HCV immunopathogenesis.MethodsParticipants in the ATAHC study, a prospective study of recent HCV infection, with detectable HCV RNA at the time of HCV detection were included. Plasma levels of 27 cytokines and chemokines were measured and their correlation with ALT and HCV RNA levels were assessed. Log10 transformed cytokines and ALT values were used in the analysis.ResultsAmong 117 individuals, the plasma levels of interferon-gamma inducible protein-10 (IP-10) and macrophage inflammatory protein-1beta (MIP-1β) were positively correlated with ALT levels (IP-10: r = 0.42, P < 0.001; MIP-1β: r = 0.29, P = 0.001) and HCV RNA levels (IP-10: rs = 0.44, P < 0.001; MIP-1β: rs = 0.43, P < 0.001). Using linear regression, after adjusting for sex, age, infection duration, symptomatic infection, HIV co-infection, interferon-lambda rs12979860 genotype, HCV genotype, and assay run, higher ALT levels (β = 0.20; 95 % CI: 0.07, 0.32; P = 0.002) and HCV RNA levels >400,000 IU/mL (vs. <8,500 IU/mL; β = 0.16; 95 % CI: 0.03, 0.28; P = 0.014) were independently associated with higher IP-10 levels. HCV RNA levels >400,000 IU/mL (vs. <8,500 IU/mL; β = 0.16; 95 % CI: 0.01, 0.31; P = 0.036) were associated with higher MIP-1β levels.ConclusionsDuring acute HCV infection, high ALT and HCV RNA levels were associated with increased IP-10 levels, while high HCV RNA levels were also associated with increased MIP-1β levels. These data suggest that IP-10 and MIP-1β may have a role in HCV immuno-pathogenesis starting early in acute HCV infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-016-0482-x) contains supplementary material, which is available to authorized users.

Highlights

This study assessed the association of alanine-aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels with pro-inflammatory and pro-fibrogenic cytokines and chemokines during acute HCV infection to provide further insight into the potential HCV immunopathogenesis
Factors associated with alanine aminotransferase (ALT) and HCV RNA levels Factors associated with ALT levels (Additional file 1: Table S2) and HCV RNA levels were assessed
Older age, symptomatic HCV, HIV co-infection, estimated duration of infection

Summary

Introduction

This study assessed the association of alanine-aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels with pro-inflammatory and pro-fibrogenic cytokines and chemokines during acute HCV infection to provide further insight into the potential HCV immunopathogenesis. Several studies have demonstrated that while elevation of alanine aminotransferase (ALT) is an important predictor of the development and progression of liver fibrosis in chronic HCV infection, HCV RNA levels have limited role in this regard (reviewed in [4, 5]). This supports a hypothesis suggesting a more important role of intra-hepatic inflammation in development and progression of liver fibrosis than direct HCV cytotoxicity in HCV infection. Further investigation of the factors associated with ALT levels in acute HCV infection may provide a better understanding of immunopathogenesis of HCV infection

Methods

Results

Conclusion