title: Discontinuation of lamivudine treatment in HBeAg-negative chronic hepatitis B: a pilot study with long-term follow-up.
abstract: BACKGROUND
  Finite treatment of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) with nucleoside/nucleotide analogues (NAs) is important in resource-limited countries. Outcome of treatment discontinuation in patients on long-term lamivudine (LVD) was assessed in a single centre observational pilot study in the current study.
  
  
  METHODS
  Non-cirrhotic patients on LVD for at least 5 years with undetectable HBV DNA on at least two consecutive assessments were offered to stop treatment. Biochemical, serological and virological measures were determined at 3-6 month intervals after treatment discontinuation. Serum quantitative hepatitis B surface antigen (HBsAg) was determined at treatment discontinuation and 5-6 years thereafter. NA treatment was re-instituted in patients with confirmed viral rebound defined as HBV DNA >20,000 IU/ml. Relapser patients were no longer followed but were re-assessed 6 years after treatment cessation.
  
  
  RESULTS
  LVD was discontinued in 23 patients. 8 patients relapsed within 1 year and NA treatment was restarted; 15 patients (65%) were non-relapsers. Thirteen of them were followed for at least 5 years. Two patients had undetectable HBV DNA throughout the follow-up period. In the rest, HBV DNA fluctuated at low levels. Two patients cleared HBsAg 24 and 36 months after stopping treatment. Quantitative HBsAg levels 5-7 years after treatment discontinuation were lower in non-relapser compared to relapser patients (1.21 IU/ml ±0.98 versus 2.71 ±0.76; P=0.002). Of 8 relapser patients 1 patient had HBsAg levels less than 100 IU/ml compared to 11 out of 13 non-relapser patients (P=0.0022).
  
  
  CONCLUSIONS
  These data suggest that cessation of NA treatment is a viable option after a reasonable treatment duration in patients with HBeAg-negative CHB and that HBsAg clearance may become an achievable target in these patients.
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Karakaya
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
authors.forename: Sevil
authors.initials: S
authors.lastname: Özer
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
authors.forename: Çağdaş
authors.initials: Ç
authors.lastname: Kalkan
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
authors.forename: E Ali
authors.initials: EA
authors.lastname: Tüzün
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
authors.forename: Aysun
authors.initials: A
authors.lastname: Çalışkan
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
authors.forename: Onur
authors.initials: O
authors.lastname: Keskin
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.
authors.forename: Gökhan
authors.initials: G
authors.lastname: Kabaçam
authors.affiliation: Hepatology Institute, University of Ankara, Ankara, Turkey.
authors.forename: Senem
authors.initials: S
authors.lastname: Karatayli
authors.affiliation: Hepatology Institute, University of Ankara, Ankara, Turkey.
authors.forename: Ersin
authors.initials: E
authors.lastname: Karatayli
authors.affiliation: Hepatology Institute, University of Ankara, Ankara, Turkey.
authors.forename: A Mithat
authors.initials: AM
authors.lastname: Bozdayi
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.|Hepatology Institute, University of Ankara, Ankara, Turkey.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Idilman
authors.affiliation: Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey.|Hepatology Institute, University of Ankara, Ankara, Turkey.
authors.forename: Cihan
authors.initials: C
authors.lastname: Yurdaydin
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers; D004279:DNA, Viral; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D053208:Kaplan-Meier Estimate; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use; D010865:Pilot Projects; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D006514:Hepatitis B Surface Antigens; D019259:Lamivudine