title: The effect of HLA-DQB1 alleles on virologic breakthroughs during chronic hepatitis B treatment with genetically low barrier drugs.
abstract: BACKGROUND
  Chronic hepatitis B treatment with oral antiviral drugs is a long course. During this course, antiviral resistance is a serious issue, particularly, if genetically low barrier drugs are in use. Host immunity is accepted to have an effect on antiviral resistance development. The earliest clinical sign of drug resistance is virologic breakthrough. In this study, we aimed to investigate the relation between HLA-DQB1 alleles and virologic breakthrough events.
  
  
  METHODS
  The patient records at single institution hepatology clinic were reviewed. Local institution ethics committee approval was taken. The patients' demographic data, virologic parameters, treatment statues were noted. Patients who had received lamivudine or adefovir were recruited and grouped into two according to virologic breakthrough occurrence. Patients who were not compliant to the given treatment were excluded. Blood samples were taken for DNA extraction. HLA-DQB1 alleles were determined at high level by sequence-speciﬁc primers-polymerase chain reaction. The distribution of DQB1 alleles among groups was analyzed.
  
  
  RESULTS
  One hundred ninety-eight patients were eligible for the study. Ninety-six of them had virologic breakthrough where 102 did not have. DQB1 0503 allele was more frequent in patients without breakthrough (28.4% vs. 12.4%, P=0.006). In univariate analysis, HBeAg seropositivity (P<0.001), absence of cirrhosis (P=0.007), younger age (P=0.002) and higher pretreatment logDNA (P<0.001) were related to breakthrough events. However, in multivariate analysis only logDNA (P<0.001) and DQB1*0503 (P=0.02) allele revealed statistically significant relation with breakthrough events.
  
  
  CONCLUSIONS
  Host immunity may have an effect on outcome during treatment with oral antiviral drugs. A patient with better immunologic profile may suppress the viral replication better and this may cause less resistance occurrence during treatment with genetically low barrier drugs.
authors.affiliation: Department of Gastroenterology, Goztepe Teaching and Research Hospital, Medeniyet University, Istanbul, Turkey. levent.doganay@ueh.gov.tr
authors.forename: Levent
authors.initials: L
authors.lastname: Doganay
authors.forename: Ilyas
authors.initials: I
authors.lastname: Tuncer
authors.forename: Seyma
authors.initials: S
authors.lastname: Katrinli
authors.forename: Feruze Yilmaz
authors.initials: FY
authors.lastname: Enc
authors.forename: Oguzhan
authors.initials: O
authors.lastname: Ozturk
authors.forename: Yasar
authors.initials: Y
authors.lastname: Colak
authors.forename: Celal
authors.initials: C
authors.lastname: Ulasoglu
authors.forename: Gizem
authors.initials: G
authors.lastname: Dinler
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D063065:Organophosphonates / Q000494:pharmacology* / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood
chemical_list: D000998:Antiviral Agents; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D063065:Organophosphonates; D012367:RNA, Viral; D019259:Lamivudine; C053001:adefovir; D000225:Adenine