Hepatitis B virus X gene mutation with predominance A1762T+G1764A double mutation on chronic liver disease patients in Surabaya, Indonesia

Background: HBV infection is a major problem worldwide, especially in developing countries including Indonesia. Mutations in the HBV gene X are commonly found in patients with CLD, especially in cirrhosis and hepatocellular carcinoma. Mutations in the X gene can cause loss of stability, increased transactivation function, and decreased anti-apoptotic ability of HBx protein. Aim: The aim of this study was to detect HBV X gene mutations in CLD patients in Surabaya. Methods: This was a cross sectional research taking samples at Dr. Soetomo General Hospital, Surabaya, Indonesia. This study used nested PCR by targeting HBV X gene. Samples showing positive HBV DNA PCR results were followed by sequencing and X gene mutation analysis by comparing sequencing results with reference strains. Results: In this study, 30 samples of CLD patients with positive HBsAg in Dr. Soetomo Surabaya were obtained. From the results of the multiple alignments, 12/30 samples (40%) had mutations on HBV X region which overlapped with Core Promoter region. There were 3 types of substitution mutations on HBV X gene (C1632T, T1753A/C/G, A1762T, and G1764A) with the dominant mutation types were A1762T and G1764A mutations, in which both mutations were found together as double mutation. Conclusion: X gene mutations were found in 40% CLD patients in Surabaya with the dominant mutation was in the form of double mutation A1762T and G1764A in 30% CLD patients in this study. The mutation was found mostly in advance stage of CLD.