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Približno 257 milijuna osoba u svijetu boluje od kronične infekcije virusom hepatitisa B, što u slučaju neliječenja dovodi do ciroze jetre ili hepatocelularnog karcinoma. Virus hepatitisa B je DNA virus s reverznom transkriptazom (RT) koja nema egzonukleaznu aktivnost, što rezultira visokom stopom mutacija. Infekcija se najčešće liječi kompeticijskim inhibitorima reverzne transkriptaze koji ometaju replikaciju virusa. Kao posljedica selekcijskog pritiska uzrokovanog terapijom, ali i imunosnim odgovorom, javljaju se mutacije koje mogu dovesti do rezistencije. Cilj ovog istraživanja bio je po prvi puta odrediti genotipove virusa HBV u 30 ispitanika iz Hrvatske te mutacije koje su odgovorne za rezistenciju na inhibitore RT kao i one odgovorne za izbjegavanje imunosnog odgovora. Sangerovim sekvenciranjem interdomene A-B gena za RT te analizom sekvencija u algoritmu Geno2Pheno određeni su genotipovi te tražene mutacije. Od deset HBV genotipova koji su identificirani u svijetu, u Hrvatskoj su prisutni genotip A (A2) u 20% i genotip D (D1, D2, D3) u 80% ispitanika. U dva ispitanika genotipa A detektirane su mutacije koje uzrokuju rezistenciju na inhibitore RT. Mutacije za izbjegavanje imunosnog odgovora detektirane su u 6 ispitanika genotipa A te u 8 ispitanika genotipa D. Distribucija genotipova kao i prevalencija mutacija odgovara onima zabilježenim u ostalim zemljama Europe. Approximately 257 million people in the world have had chronic hepatitis B virus infection, which, in case of non-treatment, causes liver cirrhosis or hepatocellular carcinoma. Hepatitis B virus is a DNA virus with a reverse transcriptase (RT) lacking exonuclease activity resulting in a high rate of viral mutations. Infection is mostly treated with competitive inhibitors of reverse transcriptase that obstruct the virus replication. The consequences of selective pressure caused by treatment as well as the immune response, may be the mutations leading to resistance. The goal of this research was to define the genotypes of HBV for the first time in a group of 30 examinees from Croatia and define the mutations responsible for the resistance to the RT inhibitors as well as the immuno-escape mutations. By sequencing A-B interdomain of the HBV RT gene by Sanger method and analysis of the sequences in the Geno2Pheno algorithm has determined virus genotypes and mutations. Out of the ten genotypes identified in the world, genotype A (A2) is present in 20% and genotype D (D1, D2, D3) in 80% of examinees in Croatia. In two genotype A examinees a mutation was detected, which caused resistance to the RT inhibitors. Immune-escape mutations were detected in 6 genotype A examinees and 8 genotype D examinees. Distribution of genotypes as well as the mutation prevalence are similar to those recorded in the other European countries. |
