title: Comparative evaluation of long-term monotherapies & combination therapies in patients with chronic hepatitis B: A pilot study.
abstract: OBJECTIVE
  Reduction of viraemia in patients with chronic hepatitis B virus (HBV) infection using nucleoside/nucleotide analogues reduces fatal liver disease-related events, but development of resistance in virus presents serious clinical challenge. Therefore, comparative evaluation of prolonged antiviral monotherapy and combination therapies was prospectively studied to assess their influence on viral suppression, rapidity of response, development of drug resistance and surfacing mutants in chronic liver disease (CLD) patients.
  
  
  METHODS
  A total of 158 (62eAg-ve) chronic hepatitis B patients were prospectively studied for 24 months. Final analysis was performed on patients treated with lamivudine (LAM, n = 28), adefovirdipivoxil (ADV, n = 24), tenofovir disoproxil fumarate (TDF, n = 26), entecavir (ETV, n = 25), LAM + ADV (n = 28) and LAM + TDF (n = 27). Quantitative hepatitis B virus DNA was detected using real-time polymerase chain reaction. Multiple comparisons among drugs and genotypic mutations were analyzed.
  
  
  RESULTS
  Progressive biochemical and virological response were noted with all the regimens at 24 months except LAM and ADV which were associated with viral breakthrough (VBT) in 46.4 and 25 per cent, respectively. Mutations: rtM204V (39.3%), M204V+L180M (10.7%) while rtA181V (8.1%) and rtN236T (8.3%) were observed with LAM and ADV regimen, respectively. LAM + ADV combination therapy revealed VBT in seven per cent of the cases without mutations whereas TDF, ETV and LAM + TDF therapies neither showed VBT nor mutations.
  
  
  CONCLUSIONS
  LAM was the least potent drug among all therapeutic options followed by ADV. TDF and ETV were genetically stable antivirals with a strong efficacy. Among newer combination therapies, LAM + TDF revealed more efficacy in virological remission and acted as a profound genetic barrier on long term. Hence, newer generation molecules (TDF, ETV) and effective combination therapy should be a certain choice.
authors.affiliation: Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: Manjita
authors.initials: M
authors.lastname: Srivastava
authors.affiliation: Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: Vinod Kumar
authors.initials: VK
authors.lastname: Dixit
authors.affiliation: Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: Gopal
authors.initials: G
authors.lastname: Nath
authors.affiliation: Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Jain
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000328:Adult; D004338:Drug Combinations; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage; D010865:Pilot Projects; D000068698:Tenofovir / Q000008:administration & dosage*
chemical_list: D004338:Drug Combinations; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir; D000225:Adenine; C106812:adefovir dipivoxil