O-22 DIFFERENTIAL MUTATION PATTERN ASSOCIATED WITH HEPATITIS B E ANTIGEN SEROCONVERSION BETWEEN SUBGENOTYPE F1b CLUSTERS: POTENTIAL ROLE IN PATHOGENESIS

Introduction and Objectives: Two clusters of the subgenotype F1b (basal and cosmopolitan) have recently been described. The basal cluster has been associated with the early occurrence of hepatocellular carcinoma in chronically infected patients from Alaska and Peru. In Argentina, where the cosmopolitan cluster is the most prevalent, this relationship has not been observed. In the course of chronic hepatitis B infection, mutations occur in different regions. In particular, mutations in the basal core promoter (BCP) and the preC/C regions are associated with HBe-antigen (HBeAg) seroconversion, an event related to the severity of chronic HBV infection. This study aimed to determine the HBeAg status and to characterize the molecular mutation patterns associated with HBeAg seroconversion in both subgenotype F1b clusters. Materials and Methods: Serum samples from 68 patients with subgenotype F1b chronic hepatitis B infection were analyzed. The BCP and pC/C regions were amplified and sequenced. Results: Twenty-one samples belonged to the basal cluster and 47 to the cosmopolitan cluster. No differences in age or gender were observed between the cases of both clusters. The basal cluster samples showed a lower frequency of positivity for HBeAg (38.1 vs. 57.4 %). In HBeAg negative samples, the basal cluster showed significantly higher rates of A1762T/G1764A (92.3 vs. 50.0, p:0.013) and G1896A (92.3 vs. 20.0, <0.001) mutations in relation to the cosmopolitan cluster. Conclusions: The disparity observed in HBeAg positivity frequency suggests that the basal cluster would be associated with earlier HBeAg seroconversion than the cosmopolitan cluster. The frequency of mutations associated with a worse clinical outcome was significantly higher in the basal cluster samples.Overall, this study provides new insights into the role of viral variants in the pathogenesis of chronic HBV infection and contributes to identifying molecular determinants associated with the pathogenesis of chronic HBV infection.