title: Virological response and antiviral resistance mutations in chronic hepatitis B subjects experiencing entecavir therapy: an Indian subcontinent perspective.
abstract: Entecavir is one of the therapeutic options currently available for the management of chronic hepatitis B. In this study, we aimed to analyse the virological response and antiviral resistance mutations in chronic hepatitis B subjects experiencing entecavir therapy from the Indian subcontinent. A total of 45 chronic hepatitis B subjects were studied at baseline and were followed up on entecavir treatment. Among these subjects, 25 (56%) were HBeAg-positive at baseline. Virological response was measured by hepatitis B virus (HBV) DNA levels. HBV reverse transcriptase (rt) domains were sequenced for the identification of resistance mutations. Three-Dimensional (3D) model of HBV polymerase/rt protein, docking and molecular dynamics simulation (MDS) studies were performed for characterization of antiviral resistance mutations. At the median treatment duration of 6 (IQR 6-11) months, 38 (84%) showed virological response. Subjects who showed anti-HBe response demonstrated significant association with virological response (p=0.034). On sequence analysis, none of the subjects were identified with signature entecavir resistance mutations. However, one subject was exclusively detected with rtV173L mutation. Molecular modeling, docking and MDS studies revealed that the rtV173L mutation cannot confer resistance to entecavir independently. Our findings also showed that the prevailing HBV genotypes, subgenotypes and HBsAg subtypes in this population does not influence treatment outcome to entecavir therapy. In conclusion, entecavir is a potent drug in terms of viral DNA suppression. In addition, none of the subjects developed antiviral resistance mutations to entecavir. Therefore entecavir is a suitable drug of choice in the management of chronic HBV.
authors.affiliation: Department of Clinical Virology, Christian Medical College, Vellore 632004, Tamil Nadu, India.
authors.forename: Ashrafali Mohamed
authors.initials: AM
authors.lastname: Ismail
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Sharma
authors.forename: Muthuvel Suresh
authors.initials: MS
authors.lastname: Kumar
authors.forename: Chundamanil Eapen
authors.initials: CE
authors.lastname: Eapen
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kannangai
authors.forename: Priya
authors.initials: P
authors.lastname: Abraham
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D012194:RNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins; C413685:entecavir; D006147:Guanine; D012194:RNA-Directed DNA Polymerase