title: HBV DNA suppression and HBsAg clearance in HBeAg negative chronic hepatitis B patients on lamivudine therapy for over 5 years.
abstract: OBJECTIVE
  In long-term responder patients, it is unclear whether lamivudine (LAM) monotherapy should be continued or switched to a high-genetic-barrier analogue. This study aims at assessing LAM efficacy over a 5-year period and the residual risk of drug resistance. The rate of HBsAg clearance and LAM long-term safety profile were also evaluated.
  
  
  METHODS
  One hundred and ninety-one patients with chronic HBeAg-negative hepatitis B successfully treated with LAM monotherapy for at least 5 years were included. Biochemical and virological tests were assessed every 3 months in all patients and HBsAg quantification was performed in 45/191. Reverse-transcriptase (RT) region was directly sequenced in virological breakthrough patients.
  
  
  RESULTS
  One hundred and ninety-one patients (148 males, median age 53 years, 72 with compensated cirrhosis) responding to 60-month LAM monotherapy continued to receive LAM monotherapy beyond the initial 5 years and were followed for an additional 36-month median period (range 1-108). Virological response was maintained in 128/191 patients (67%) and HBsAg clearance was observed in 15/128 (11.7%) after a 32-month median period (range 1-65). The 63 remaining patients (33%) showed virological breakthrough after a 15-month median treatment (range 1-78). RT region analysis was performed in 38/63 breakthrough patients and LAM resistant mutations were found in 37/38. No significant side effects were observed.
  
  
  CONCLUSIONS
  In long-term responder patients, continuation of LAM monotherapy resulted in persistent viral suppression in most cases with undetectable HBV DNA by real-time PCR; moreover, 11.7% of these patients cleared HBsAg. Selection of LAM resistance, however, can still occur even after successful long-term therapy, thus emphasising the importance of a careful virological monitoring.
authors.affiliation: Clinic of Infectious Diseases, University of Bari, Policlinico, Bari, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Fasano
authors.forename: Pietro
authors.initials: P
authors.lastname: Lampertico
authors.forename: Alfredo
authors.initials: A
authors.lastname: Marzano
authors.forename: Vito
authors.initials: V
authors.lastname: Di Marco
authors.forename: Grazia Anna
authors.initials: GA
authors.lastname: Niro
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Brancaccio
authors.forename: Andrea
authors.initials: A
authors.lastname: Marengo
authors.forename: Gaetano
authors.initials: G
authors.lastname: Scotto
authors.forename: Maurizia Rossana
authors.initials: MR
authors.lastname: Brunetto
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Gaeta
authors.forename: Mario
authors.initials: M
authors.lastname: Rizzetto
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Angarano
authors.forename: Teresa
authors.initials: T
authors.lastname: Santantonio
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D019259:Lamivudine