Recognition mechanisms of innate immune response help to improve immunotherapeutic strategies in HBeAg-negative chronic hepatitis B (CHB). Toll-like receptor 2 (TLR2) is an important component of innate immunity. In this study, the frequency of precore mutations of the hepatitis B virus (HBV) and serum TLR2 were evaluated in CHB patients. Fifty-one patients with chronic hepatitis B, negative for HBeAg and detectable HBV DNA, were examined for the presence of mutations in pre-core region of HBV genome by direct sequencing. Serum TLR2 was measured by enzyme-linked immunosorbent assay. Interactions of truncated HBeAg and TLR2 proteins were evaluated with molecular docking software. The G1896A pre-core mutation were detected in 29 (57%) which was significantly associated with higher concentration of serum TLR2 in comparison with patients without this mutation (4.8 2.9 versus 3.4 2.2？ng/mL, ). There was also a significant correlation between serum ALT and TLR-2 ( ; ). Docking results illustrated residues within the N-terminus of truncated HBeAg and TLR2, which might facilitate the interaction of these proteins. These findings showed the dominance of G1896A pre-core mutation of HBV variants in this community which was correlated with serum TLR2. Moreover TLR2 is critical for induction of inflammatory cytokines and therefore ALT elevation. 1. Introduction Hepatitis B virus (HBV) infection is an important cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) [1]. The transmission of HBV from infected mothers to neonates causes persistent infection [2]. Chronic infection of HBV is a global health problem. However, the prevalence and genotype distribution of HBV are different among the geographical areas [3]. The majority of chronic hepatitis B patients lose HBe antigen (HBeAg) and develop anti-HBe antibody, which is generally associated with a decrease in serum HBV DNA levels and a gradual accumulation of precore or core promoter mutations [4]. HBeAg-negative chronic hepatitis B is the predominant type of CHB in Mediterranean inhabitants [3]. Two types of precore and core promoter HBV mutations that reduce HBeAg formation are more frequent in regions where patients are predominantly infected with HBV genotype D [4, 5]. Infection with wild-type strains of HBV often induces mild symptoms and responds well to interferon alpha therapy, but patients infected with precore mutant variants may show clinical evidence of elevated or fluctuating ALT and HBV DNA [6]. The reason that precore negative mutants become predominant in some patients during
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