title: Mutational analysis of reverse transcriptase and surface proteins of patients with partial virological response during mono and combination antiviral therapies in genotype D chronic hepatitis B.
abstract: BACKGROUND
  The mutational pattern of chronic Hepatitis B virus (HBV) is unclear in patients who show incomplete response to antiviral therapy. The aims of this study were 1) to determine the benefit of combination therapy with adefovir dipivoxil (ADV) and Lamivudine (LAM) versus ADV or LAM alone in maintaining virological, biochemical and histological responses and 2) to investigate the patterns of mutations in the reverse transcriptase and surface proteins of HBV with LAM and/or ADF-resistant in partially-responded chronic hepatitis B (CHB) patients.
  
  
  METHODS
  The study group consisted of 186 chronic HBV carriers who were admitted to the Tehran Hepatitis Network from 2010 to 2013. We retrospectively selected 86 patients who partially responded to different nucleoside analogue regimens. After 48 weeks of therapy, five groups of patients were defined including eight Lamivudine (LAM) Group (I), 30 Adefovir (ADV) Group (II), 16 ADV add on LAM Group (III), 32 ADV+LAM Group (IV), and 100 controls (no therapy). Reverse transcriptase (RT) and surface genes were amplified and sequenced for mutational analysis.
  
  
  RESULTS
  All groups showed differences between mean values for age, gender, alanine transaminase (ALT), aspartate transaminase (AST), and HBV DNA levels groups showed significant differences than other groups (p < 0.05). The mutation frequencies for groups were I (1.7%), II (1.39%), III (2.28%), IV (2.0%), and V (0.38%). T54N, L80I/V, I91L/V, L180M, M204I/V, Q215P/S, and F221Y/S showed the highest number of mutations in all groups with different frequencies. Four new, unreported mutations were found.
  
  
  CONCLUSIONS
  Those patients who failed to respond in the first 48 weeks, whether they were receiving mono or combination therapy, should be tested genotypically, for the early modification of treatment.
authors: Ph.D. of Medical Virology, Assistant Professor, Department of Microbiology, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors: Mostafa
authors: M
authors: Mahabadi
authors: MD Of Gastroenterology, Professor, Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors: Seyed Moayed
authors: SM
authors: Alavian
authors: Ph.D. of Molecular Genetics, Assistant Professor, Department of Virology, School of Public Health Tehran University of Medical Sciences, Tehran, Iran.
authors: Mehdi
authors: M
authors: Norouzi
authors: Ph.D. of Medical Virology, Associate Professor, Department of Virology, Iran University of Medical Sciences, Tehran, Iran.
authors: Hossein
authors: H
authors: Keyvani
authors: Ph.D. of Epidemiology and Biostatistics, Professor, Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors: Mahmood
authors: M
authors: Mahmoudi
authors: MD, Ph.D. of Clinical Virologist, Associate Professor, Hepatitis B Lab-Dept. Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors: Seyed Mohammad
authors: SM
authors: Jazayeri
keywords: drug resistant variants; hepatitis; hepatitis b virus; nucleoside analogues (NA); partial response