Hepatitis B caused by infection with the Hepatitis B Virus (HBV) has been a problem throughout the world, especially in developing countries. In Indonesia, people with hepatitis B have a high incidence rate. The Hepatitis B virus is a DNA virus that is not stable. HBV cannot correct genes as well as DNA viruses in general so that HBV easily mutates. HBV gene has four reading frames, Surface, Polymerase, Core, and X.
Of the four reading frames, the region of the X gene is able to integrate into the host genome and cause changes in the cell signaling pathway in the host body. In various researches conducted overseas, mutations in the HBV X gene region are often found in hepatitis B sufferers with chronic liver disease. Chronic liver disease is divided into three stages, namely chronic hepatitis, liver cirrhosis, and liver cancer. A mutation is defined as a change in the nucleotide arrangement of a virus which has an impact on changes in the protein produced by the virus. The HBV X gene mutation can interfere with the stability of protein X produced by the hepatitis virus. Therefore, the normal function of protein X can be disrupted and transformed to trigger malignancy. A mutation on the X gene region can also affect other regions of HBV frames because the location of X gene overlapped with the other regions of HBV.
The research conducted by Wungu et al. (2019) published in Malaysian Journal of Biochemistry and Molecular Biology aimed at detecting the presence of HBV X gene mutations in patients with chronic liver disease in Surabaya. It was conducted because research on the mutation of X genes in Indonesia, including Surabaya, is still limited. The research took a sample of 30 patients with chronic liver disease with hepatitis B in Dr. Hospital. Soetomo, Surabaya, Indonesia. It used advanced molecular techniques in the form of nested PCR- direct sequencing, which was done at Universitas Airlangga Laboratory of Hepatitis Institute of Tropical Disease (ITD). The genetic composition of the virus known from the procedure is then compared with the normal genetic composition of HBV to find out if there is a mutation.
The results of the research showed that there were 40% or 12 patients out of total samples of patients in Surabaya experiencing mutation in the X gene. It shows the high incidence of hepatitis B mutations in Surabaya. There are three types of X gene mutations in the research, C1632T, T1753A / C / G, A1762T, and G1764A. The types of mutations dominating are A1762T and G1764A as multiple mutations. These mutations are generally found in advanced stages of chronic liver disease.
This multiple mutations has a lot to do with the development of hepatitis B into liver cancer. This HBV strain with multiple mutations is said to have a higher survival advantage than a single mutation. It is indicated by higher HBV replication found in HBV with multiple mutations. This high HBV replication causes an increase in inflammation, replication, and viral invasion. This double mutation is also said to be able to suppress the expression of malignant cell control regulators strongly that it causes uncontrolled cell proliferation.
Research on the mutation of HBV X gene in Indonesia itself is still very limited. The frequency of K130M / V131L multiple mutations in this research was found to be higher than in previous research. The number of mutations in the HBV X gene found in this research made us realize that there is also a possibility that many mutations occur in other HBV regions. There is also a possibility of different mutation patterns in various regions and tribes in Indonesia. A1762T and G1764A as dominant mutations can be further studied as predictors of chronic liver disease with hepatitis B. This allows hepatitis B sufferers to be able to take precautions and treat them earlier before falling into an advanced stage of chronic liver disease.
Author: Citrawati Dyah Kencono Wungu, dr., M.Si
Details of this research available at:
https://msbmb2010.wixsite.com/mjbmb
https://drive.google.com/file/d/1n6xqRy6LfJ2ZNVMW54u5wN01uq5q2Pso/view
Citrawati Dyah Kencono Wungu, Mochamad Amin, S. Eriaty N. Ruslan, Priyo Budi Purwono, Ulfa Kholili, Gwenny Ichsan Prabowo, Ummi Maimunah, Poernomo Boedi Setiawan, Maria Inge Lusida, Soetjipto, Retno Handajani (2019). Hepatitis B Virus X Gene Mutation with Predominance A1762T+G1764A Double Mutation on Chronic Liver Disease Patients in Surabaya, Indonesia. Malaysian Journal of Biochemistry and Molecular Biology, 22(1): 27-31
