A mutation in the interferon regulatory element of HBV may influence the response of interferon treatment in chronic hepatitis B patients

Abstract

Background: A functional interferon regulatory element (IRE) has been found in the EnhI/X promoter region of hepatitis B virus (HBV) genome. The purpose of this study is to compare the gene order of responder and non-responder to interferon therapy in patients with chronic hepatitis B (CHB), so as to evaluate the relationship between IRE mutation and the response to interferon treatment for CHB patients.

Results: Synthetic therapeutic effect is divided into complete response (CR), partial response (PR) and non-response (NR). Among the 62 cases included in this study, 40 cases (64.5%) were in the response group (CR and PR) and 22 (35.5%) cases were in the NR group. Wild type sequence of HBV IRE TTTCACTTTC were found in 35 cases (56.5%), and five different IRE gene sequences. included TTTtACTTTC, TTTCAtTTTC, TTTtAtTTTC, TTTtACTTTt and cTTtACcTTC, were found in 22 cases (35.5%), 1 case (1.6%), 1 case (1.6%), 2 cases (3.2%) and 1 case (1.6%) respectively. There were 41.9%cases (26/62) with forth base C→T mutation, consisted of 32.5% (13/40) cases in response group and 59.1% (13/22) cases in NR group. Among the 35 cases with IRE sequences, there were 67.5% (27/40) cases in response group and 36.4% (8/22) in NR group, and the difference in IRE sequences between two groups was statistic significantly (P = 0.027). The result suggested that there is likely relationship between the forth base mutation (C→T) of IRE region and the response of HBV to Interferon therapy, and this mutation may partially decrease the inhibition effect of interferon on HBV.

Conclusion: The forth base C→T mutation in IRE element of HBV may partially influence the response of Interferon treatment in CHB patients.

Figure 1

PCR products of HBV DNA including IRE region from the serum of patients and control. M: DNA marker DL2000 A: pHBV4.1 plasmid B: pBHB 4 plasmid C: Chronic hepatitis B patient's serum(positive control) D-F:our patient's serums G:PAd/NS3 plasmid H: Serum of normal person I: TE (blank control).

Figure 2

IRE sequences of wild strains and mutation strains. A: wild strain B: forth base point mutation(C→T) C: sixth base point mutation(C→T) D: forth base point mutation(C→T) and sixth base point mutation(C→T) E: forth base point mutation(C→T) and tenth base point mutation(C→T) F: first base point mutation(T→C), forth base point mutation(C→T) and seventh base point mutation(T→C).