Dna polymerase gen mutations of HBV strains in hepatitis B infection and lamivudine, adefovir, entecavir, telbivudine and tenofovir drug resistance analysis

Hepatitis B virus (HBV) infections, are important public health problem in our country as well as all over the world. Two billion people on earth have encountered with HBV, 400 million of them are HBV carriers. Althought HBV infection is clinically seen as acute, fulminant, chronic hepatitis or chronic carrier, it may also cause liver cirrhosis and hepatocellular carcinoma (HCC). One million people die from the reasons like cirrhosis and HCC associated with HBV each year. 60-80% of HCC cases are associated with HBV in the world. DNA level is an important criterion for evaluation of the regulation of treatment and consideration of antiviral response in patients with HBV. Recently, increased resistance development monitored against nucleotide analogues in treated patients and high cost treatment can be failed. The main reason for the development of the resistance against antiviral agents is the high error rate of HBV polymerase enzyme and becoming dominant of mutant strains as a result of long term drug use and undergoing selection. At this study, HBV DNA level, serological and biochemical test results were evaluated in patients with chronic Hepatitis B and mutations cause to antiviral resistance likely to occur in DNA polymerase gene were researched. This study was carried out in Şahinbey Hospital of Gaziantep University, between Marc 2012- January 2013. Samples were selected among the patients with serum positive HBsAg and HBV DNA as a result of routine tests sent from various polyclinics with HBV pre-diagnosis. A Toplam of 99 patients included in the study that 64 (64.6%) of them were male and 35 (35.4%) of them were female. From the patients, 79.8% were adults and 20.2% were children. The relationship between biochemical parameters (ALT, AST), hepatitis markers (HBsAg, HBeAg) and the levels of HBV DNA were compared. As a result of the study, statistically significant relationship was found between serum HBsAg, HBeAg, transaminases (ALT, AST) and the levels of HBV DNA. In addition, DNA polymerase gene mutations which determine the development of resistance against antiviral drugs were investigated by pyrosequence DNA sequencing method (Pyromark Q24, QIAGEN, Germany). For this purpose, drug resistance mutation analyze was made by sequencing of codons numbered 169, 173, 180, 181, 184, 194, 202, 204, 236 and 250. In only one patient, Lamivudine resistance was detected as a result of mutation occurred in codon 204 and turning of methionine into valine. For the planning of treatment, as well as the detection of levels of HBV DNA, the investigation of resistance developed against antivirals also become important. Therefore, this study is important in terms of the detection of drug resistance in our region. Key words: Hepatitis B, HBV DNA, HBsAg, HBeAg, ALT, AST, pyrosequence analysis, drug resistance