Abstract
Histone acetylation has been demonstrated to serve a pivotal role in numerous inflammatory diseases. The present study examined histone acetylation in patients with chronic hepatitis B (CHB) and CHB with liver failure by detecting histone deacetylase (HDAC) activity. Mice with acute liver failure (ALF) were treated with the HDAC inhibitor entinostat (MS275) and alterations in HDAC activity and pro‑inflammatory cytokine expression levels were detected. The effect of HDAC1 silencing on LPS-treated RAW264.7 murine macrophages was examined using specific small interfering RNA sequences, and the acetylation level of the non‑histone nuclear factor‑κB (NF‑κB) p65 subunit was additionally examined. The results demonstrated that serum levels of alanine aminotransferase, aspartate aminotransferase and total bilirubin, and the expression levels of pro‑inflammatory cytokines, were significantly increased in patients with CHB. Aberrant histone acetylation and HDAC activity were identified in patients with CHB, with their levels associating with disease severity. MS275 treatment may decrease HDAC activity and inhibit the production of cytokines; however, acetylation levels of H3 and H4 were enhanced. Acetylation levels of NF‑κB p65 were decreased in lipopolysaccharide‑treated cells and ALF mice, and were promoted by MS275 treatment and HDAC1 silencing. In conclusion, alterations in HDAC activity and expression levels demonstrated a greater effect on inflammation compared with histone acetylation; therefore, the underlying mechanisms may be associated with the acetylation of non-histones. These results provide a potential novel therapeutic strategy for the treatment of CHB.