Novel X gene point mutations in chronic hepatitis B and HBV related cirrhotic patients

HBx is a multifunctional modulator viral protein with key roles in various biological processes such as signal transduction, transcription, proliferation, and cell apoptosis. Also, HBx has an important role in the progression of cirrhosis and hepatocellular carcinoma (HCC). This study aimed to determine mutations in X gene, enhancer II (EnhII), and basal core promoter (BCP) of genotype D of Hepatitis B Virus (HBV) in cirrhotic and chronic HBV patients.

This cross-sectional study was performed on 68 cases with chronic HBV (cHBV) and 50 cases with HBV related cirrhosis. Serum samples were obtained for genomic DNA extraction. Semi-nested PCR was used to amplify the HBx region. Point mutations in the HBx region were detected by sequencing.

Novel mutations were detected, including C1491G, C1500T, G1613T, and G1658T in the N-terminal of the X gene. The frequency of C1481T/G1479A, T1498C, C1500T, G1512A, A1635T, C1678T, A1727T, and A1762T/ G1764A/ C1773T was significantly higher in cirrhotic patients compared to chronically HBV infected ones. A higher rate of A1635T, C1678T, A1727T, A1762T, G1764A, and C1773T was observed in cirrhotic patients.

Our findings showed that the frequency of mutations in the basal-core promoter, enhancer II, and regulatory region of the HBx gene was more seen in cirrhotic patients than in chronic HBV cases. Novel mutations were detected in the HBx gene, causing amino acid substitutions; however, the clinical impact of these novel mutations is yet to be cleared.