Study the Cross-talk Between Hepatitis B Virus Infection and Interferon Regulatory Factors in Liver Transplant Patients

Abstract

Background: Interferon regulatory factors (IRFs) as immunoregulatory molecules have a determinative antiviral role in liver transplantation outcomes and graft rejection. Hepatitis B virus (HBV) and its antigen derivatives also choose some strategies to escape from innate immune responses. Objectives: The current study aimed at evaluating inflammatory cross-talks between pattern recognition receptors (PRRs) signaling components such as IRF3 and IRF7 with HBV infection in mRNA levels in patients undergoing liver transplantation. Methods: The 46 HBV infected liver recipients were divided into rejection experienced (20) and not experienced (26) groups and a healthy control group was also considered. Peripheral mononuclear cells (PBMCs) were isolated form each studied patient on the days 1, 4, and 7 in post-transplant period. After RNA extraction and cDNA synthesis from each collected sample, the expression levels of IRF3 and IRF7 genes were evaluated using in-house SYBER Green based the real-time polymerase chain reaction (PCR) protocols. Results: The overexpression of mRNA levels of IRF3 (3.37 folds) and IRF7 (1.74 folds) on the day 1 were found in patients experiencing rejection, compared with non-rejected ones, based on initial ischemia/reperfusion (I/R) injuries. But, the mRNA levels of IRF3 (0.53 folds) and IRF7 (0.74 folds) on the day 4 were downregulated in patients with rejected transplantation, compared with non-rejected ones. Finally, reducing the expression of IRF3 (0.54 fold) on the day 7 and upregulation of IRF7 (2.38 fold) on the day 7 were found in rejected liver recipients, compared with non-rejected ones in post-transplant period. Conclusions: Downregulation of IRF3 expression in patients with HBV infection, who experienced rejection episodes in the first week post-liver transplantation indicated that they may be at higher risk for acute rejection; the hypothesis, which should be investigated in further studies.