title: Lamivudine monotherapy in chronic hepatitis B patients from the Indian subcontinent: antiviral resistance mutations and predictive factors of treatment response.
abstract: OBJECTIVE
  Management of chronic hepatitis B is a global public health challenge. There are several updated guidelines proposed based on treatment outcome data from the respective study populations. In this study, we aim to characterize the antiviral resistance mutations to lamivudine monotherapy in patients diagnosed with chronic hepatitis B from the Indian subcontinent.
  
  
  METHODS
  A total of 147 lamivudine-treated patients with a median treatment duration of 13 (interquartile range 8-24) months were studied. Virological response was measured by hepatitis B virus (HBV) DNA levels. Antiviral resistance mutations were identified by sequencing HBV reverse transcriptase domains. Factors associated with virological response and antiviral resistance mutations were analyzed.
  
  
  RESULTS
  Virological response was observed in 50 (35 %) patients while 84 (57 %) were non-responders. The virological response for the remaining 13 (9 %) patients was undetermined. Forty patients (27 %) developed lamivudine-resistant mutations. HBV genotypes, subgenotypes and hepatitis B surface antigen subtypes did not show significant association with virological response or lamivudine-resistant mutations. High HBV DNA levels and increased treatment duration were strongly associated with the development of lamivudine-resistant mutations (p = 0.002 and p < 0.001). Patients who continued to be positive for hepatitis B e antigen have an increased risk for treatment failure (p = 0.010). High baseline aspartate transaminase levels were significantly associated with subsequent lamivudine response (p = 0.037).
  
  
  CONCLUSIONS
  Considering the limited potency and high resistance rates to lamivudine therapy, our study emphasizes the use of more potent drugs in the management of chronic hepatitis B in the Indian subcontinent.
authors.affiliation: Department of Clinical Virology, Christian Medical College, Vellore, 632 004, Tamil Nadu, India.
authors.forename: Ashrafali Mohamed
authors.initials: AM
authors.lastname: Ismail
authors.forename: Prasanna
authors.initials: P
authors.lastname: Samuel
authors.forename: Jeyamani
authors.initials: J
authors.lastname: Ramachandran
authors.forename: Chundamannil 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*; D004279:DNA, Viral / Q000032:analysis; D024882:Drug Resistance, Viral; D005260:Female; D005819:Genetic Markers; D006513:Hepatitis B e Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007194:India; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D005819:Genetic Markers; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine
references.citation: J Med Virol. 2002 Nov;68(3):311-8
references.pmid: 12226816
references.citation: Lancet. 2001 Mar 24;357(9260):934-5
references.pmid: 11289355
references.citation: J Clin Microbiol. 2011 Sep;49(9):3215-21
references.pmid: 21795507
references.citation: Antiviral Res. 2010 Dec;88(3):269-75
references.pmid: 20875460
references.citation: Semin Liver Dis. 2006 May;26(2):162-70
references.pmid: 16673294
references.citation: Hepatology. 2001 Oct;34(4 Pt 1):785-91
references.pmid: 11584376
references.citation: Intervirology. 2012;55(1):36-44
references.pmid: 21311172
references.citation: Hepatology. 2007 Dec;46(6):1695-703
references.pmid: 18027877
references.citation: Hepatology. 1998 Jun;27(6):1670-7
references.pmid: 9620341
references.citation: J Hepatol. 2003;39 Suppl 1:S93-8
references.pmid: 14708685
references.citation: J Viral Hepat. 2006 Apr;13(4):278-88
references.pmid: 16611195
references.citation: N Engl J Med. 1999 Oct 21;341(17):1256-63
references.pmid: 10528035
references.citation: Hepatology. 2000 Jun;31(6):1318-26
references.pmid: 10827158
references.citation: J Hepatol. 2003;39 Suppl 1:S111-5
references.pmid: 14708688
references.citation: Antimicrob Agents Chemother. 2004 Sep;48(9):3498-507
references.pmid: 15328117
references.citation: J Viral Hepat. 2004 Mar;11(2):97-107
references.pmid: 14996343
references.citation: Lancet Infect Dis. 2008 Mar;8(3):167-78
references.pmid: 18053766
references.citation: Gastroenterology. 2003 Dec;125(6):1714-22
references.pmid: 14724824
references.citation: Hepatology. 2002 Jul;36(1):186-94
references.pmid: 12085364
references.citation: Clin Infect Dis. 2002 May 1;34(9):1273-7
references.pmid: 11941556
references.citation: World J Gastroenterol. 2012 Feb 28;18(8):800-5
references.pmid: 22371640
references.citation: Hepatology. 2000 Nov;32(5):1078-88
references.pmid: 11050059
references.citation: Clin Liver Dis. 2005 May;9(2):191-211, v
references.pmid: 15831268
references.citation: J Hepatol. 2009 Feb;50(2):227-42
references.pmid: 19054588
references.citation: Antiviral Res. 1996 Jan;29(1):31-3
references.pmid: 8721540
references.citation: Intervirology. 2007;50(1):45-51
references.pmid: 17164557
references.citation: Antivir Ther. 2008;13(2):211-20
references.pmid: 18505172
references.citation: J Hepatol. 2005 Jul;43(1):72-7
references.pmid: 15896869
references.citation: J Gastroenterol Hepatol. 2009 Mar;24(3):346-53
references.pmid: 19220670
references.citation: Clin Infect Dis. 2003 Mar 15;36(6):687-96
references.pmid: 12627352