title: GENOMIC ANALYSIS OF HEPATITIS B VIRUS STRAINS INFECTING ROMANIAN PATIENTS.
abstract: Chronic hepatitis B is widespread and represents an important cause of morbidity and mortality due to the evolution to cirrhosis and hepatocellular carcinoma. This study was designed to improve the national laboratory surveillance of hepatitis B virus (HBV) infection, focusing on genomic analysis of isolates from Romanian patients. Sera from ten patients with HBV were collected and analyzed. Phylogenetic analysis was conducted on a DNA fragment spanning almost the entire genome. The occurrence of mutations was assessed for each open reading frame in the viral genome. Phylogenetic analysis revealed five isolates belonging to genotype A (subgenotype A2) and other five clustering with genotype D strains (subgenotype D1). Two patients treated with lamivudine were found to carry isolates harboring rtM204V lamivudine resistance mutation. An HBV isolate displaying a lamivudine complex resistance pattern, rtM204I in conjunction with rtL180M and rtA200V, was found in a lamivudine naïve patient. All samples harbored sA105P substitution, usually found in HBIg therapy escape isolates. Three of the studied strains were simultaneously displaying T1753, T1762 and A1764 mutations which in vitro induce enhanced genome replication and reduction of HBeAg expression. The sequence obtained from a patient with decompensated liver cirrhosis presents a novel type of insertion consisting of nine nucleotides between positions 260 and 261 in the X gene. Despite the small number of samples, our findings suggest the need to determine the drug resistance pattern for each patient before taking a therapeutic decision and also highlight the necessity of knowing the real level of drug resistance among HBV strains circulating in Romania.
authors.forename: Sorin
authors.initials: S
authors.lastname: Dinu
authors.forename: Graţiela
authors.initials: G
authors.lastname: Târdei
authors.forename: Emanoil
authors.initials: E
authors.lastname: Ceausu
authors.forename: Adriana
authors.initials: A
authors.lastname: Moţoc
authors.forename: Cristiana
authors.initials: C
authors.lastname: Oprea
authors.forename: Eugenia
authors.initials: E
authors.lastname: Ungureanu
authors.forename: Luminiţa
authors.initials: L
authors.lastname: Ene
authors.forename: Dan
authors.initials: D
authors.lastname: Duiculescu
authors.forename: Dana Brehar
authors.initials: DB
authors.lastname: Cioflec
authors.forename: Gabriela
authors.initials: G
authors.lastname: Oprişan
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage; D005260:Female; D016679:Genome, Viral; D023281:Genomics; D005838:Genotype; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D012383:Romania; D000068698:Tenofovir / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000068698:Tenofovir