title: Snapshot on drug-resistance rate and profiles in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice.
abstract: While the selection of complex HBV drug-resistance patterns on therapeutic failure can compromise the efficacy of anti-HBV therapies, recent data show that patients failing treatment without drug-resistance have a rate of virological success close to drug-naive patients. The goal of this study is defining, in clinical practice, the burden of drug-resistance mutations in a cohort of patients treated with anti-HBV drugs. Prevalence and patterns of drug-resistance were analyzed by RT-sequencing in 204 patients infected chronically: 148 experiencing virological rebound (defined as an increase in serum HBV-DNA > 20 IU/ml after achieving virological success [HBV-DNA < 20 IU/ml]), and 56 null/partial responders (always detectable serum HBV-DNA [>20 IU/ml] within 48 weeks of therapy). The highest rate of drug-resistance was observed in patients experiencing virological rebound (prevalence, 79.1%). Conversely, almost half (46.4%) null/partial responders have no evidence of drug-resistance. The rate of drug-resistance was higher in patients treated with lamivudine (76.8% [109/142]) and telbivudine (83.3% [5/6]), followed by adefovir (62.5% [15/24]), and entecavir (52.2% [12/23]). Complex mutational patterns characterized by the co-presence of rtM204V/I-rtA181T/V (impairing the efficacy of all anti-HBV drugs) were detected in four patients (2.7%) with virological rebound. Drug-resistance is the main cause of failure to therapy in patients experiencing virological rebound, supporting the need of rapid switch to anti-HBV drugs with higher genetic barrier and potency (entecavir/tenofovir). Conversely, nearly half of null/partial responders shows no evidence of drug-resistance mutations, maintaining high chance of achieving therapeutic success with the same class of drug. In this setting, genotypic resistance may help in selecting patients still carrying wild-type viruses, that may take major benefits from antiviral treatment.
authors.affiliation: Department of Experimental Medicine and Surgery, University of Tor Vergata, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Salpini
authors.forename: C
authors.initials: C
authors.lastname: Alteri
authors.forename: V
authors.initials: V
authors.lastname: Cento
authors.forename: M
authors.initials: M
authors.lastname: Pollicita
authors.forename: V
authors.initials: V
authors.lastname: Micheli
authors.forename: G
authors.initials: G
authors.lastname: Gubertini
authors.forename: G M
authors.initials: GM
authors.lastname: De Sanctis
authors.forename: M
authors.initials: M
authors.lastname: Visca
authors.forename: S
authors.initials: S
authors.lastname: Romano
authors.forename: C
authors.initials: C
authors.lastname: Sarrecchia
authors.forename: M
authors.initials: M
authors.lastname: Andreoni
authors.forename: M
authors.initials: M
authors.lastname: Angelico
authors.forename: G
authors.initials: G
authors.lastname: Parruti
authors.forename: V
authors.initials: V
authors.lastname: Svicher
authors.forename: C F
authors.initials: CF
authors.lastname: Perno
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004279:DNA, Viral / Q000037:antagonists & inhibitors*; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000235:genetics; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use; D012008:Recurrence; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D000077712:Telbivudine; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine; D013936:Thymidine