Gene Expression changes in Liver Tissue from Fulminant Hepatitis E

Abstract

Background and Aim: It is unclear whether liver injury in acute hepatitis E is due to virus-induced cytolysis or the host immune response. We therefore studied host gene expression and enumerated immune cells in liver tissues from fulminant hepatitis FHE (FH-E) patients, in comparison with healthy livers and those from fulminant hepatitis B (FH-B) patients. Methods: Microarray-based expression profiling was done on post-mortem liver tissue from 5 FH-E and 6 FH-B patients, and normal liver tissue from 6 persons. Differential expression was defined as ≥2.0-fold change with Benjamini-Hochberg false discovery rate below 0.05. CD4+, CD8+ and CD56+ cells were counted using immunohistochemistry. Results: Compared to normal, the livers from FH-E and FH-B showed differential expression of 3377 (up-regulated 1703, down-regulated 1674) and 2572 (up 1164, down 1408) entities, respectively. This included 2142 (up 896, down 1246) entities that were common between the two sets; most of these belonged to metabolic, hemostatic and complement pathways. An analysis of 1235 (up 807, down 428) entities with differential expression in FH-E but not in FH-B showed activation of several immune response pathways, particularly those involving cytotoxic T cells. CD8+ T cells showed similar increase in both FH-E (median 53.4 per arbitrary unit area [range 31.2-99.9]) and FH-B (49.3 [19.3-51]; P = 0.005) compared to controls (6.9 [3.1-14.9]). Conclusion: Liver tissue from FH-E patients showed increased expression of genes belonging to cytotoxic T cell effector pathways, accompanied by CD8+ T cell infiltration. This suggests that CD8+ T cells play a role in the pathogenesis of hepatitis E.