Resting signal transducer and activator of transcription (stat) profile in liver biopsies of patients with chronic hepatitis B

AIM: To determine the characteristics of resting STAT proteins in patients with chronic hepatitis B and to study the relationship between these proteins and ALT levels, Hepatitis B Virus(HBV) DNA levels and liver histology.BACKGROUND: Increasing evidence demonstrates that activated phosphralayted-STAT proteins can regulate many pathways important in virus-host interaction.Recently it has been found that some resting unphosphorylated-STAT(u-STAT) proteins also play important roles in mediating gene expression instead of waiting as latent intracytoplasmic signalling mediators. We therefore studied the u-STATs profile and their relationships with some clinical significant determinants in the chronic hepatitis B patients.METHODS: A total of 35 (28 HBeAg negative, 7 HBeAg positive) unselected consecuitive treatment naive patients chronically infected with HBV underwent liver biopsy.Liver tissue biopsies were examined for the presence of unphosphorylated STAT1, STAT2, STAT3, STAT4, STAT5B, STAT6 expression using immunohistochemical staining. The associations between the immunostaining and viral loads and ALT levels and liver histology (Ishac scorring) were analyzed.RESULTS: Of the 35 liver biopsies examined (19 male, 16 female), 57%, 23%, 46%, 66%, 35%, 86% was positive for u-STAT1, u-STAT2, u-STAT3, u-STAT4, u-STAT5B, u-STAT6, respectively. Both of the expression of u-STAT1 and u-STAT2 were negative in the 29% of liver tissues. The absence of u-STAT4, the presence of u-STAT6 and the pattern of both absence of u-STAT1 and u-STAT2 showed significant correlations with ALT levels. The expression of u-STAT6 was associated with HBV DNA levels. In addition u-STAT2, u-STAT3 and u-STAT4 showed significant relation with necroinflammatory stage.CONCLUSION: This study showed that like activated part, resting part of the STATs had also involved in chronic hepatitis B. Understanding of STAT expression profiles may make contribution to further studies of chronic hepatitis B pathogenesis.