title: Long-term lamivudine therapy in chronic hepatitis B.
abstract: One to 5 years of therapy of chronic hepatitis B with oral nucleoside analogues result in significant clinical improvements, but effects of more prolonged therapy are not well defined.
  
  
  
  To describe outcomes of chronic hepatitis B with long-term lamivudine therapy.
  
  
  
  Forty-two patients with chronic hepatitis B treated with lamivudine were followed for 3.2-19.5 (median = 16.1) years. Therapy was switched to other agents (n = 16) if patients developed lamivudine resistance and relapse of disease.
  
  
  
  Among 22 HBeAg-positive patients, 17 (77%) became HBeAg negative, of whom 5 (23%) subsequently cleared HBsAg. Among 20 HBeAg-negative patients, 10 (50%) cleared HBsAg. The time to HBsAg clearance ranged from 0.9 to 16.8 (median = 9.3) years. Lamivudine resistance arose in 24 patients (57%) of whom 6 (25%) lost HBsAg. HBsAg clearance was not always accompanied by seroconversion; anti-HBs appearing concurrently in only five patients (33%). Nevertheless, HBsAg loss allowed for stopping therapy in all patients, none re-developing HBsAg or suffering relapse; all having normal alanine aminotransferase levels and no (n = 13) or unquantifiable HBV DNA levels (n = 2) when last seen. In contrast, seven of 27 patients (26%) who remained HBsAg-positive died of liver disease or liver cancer or underwent liver transplantation, all of whom had cirrhosis.
  
  
  
  Long-term viral suppression with nucleoside analogues leads to HBsAg loss in a substantial proportion of patients, particularly if HBeAg-negative. Serious outcomes during the first 10-20 years of treatment occur largely among patients with pre-existing cirrhosis who do not clear HBsAg with therapy.
authors.affiliation: Liver Diseases Branch, Intramural Division, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lingala
authors.affiliation: Beth Israel-Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: D T-Y
authors.initials: DT
authors.lastname: Lau
authors.affiliation: Liver Diseases Branch, Intramural Division, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Koh
authors.affiliation: NIDDK, NIH, Bethesda, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Auh
authors.affiliation: Liver Diseases Branch, Intramural Division, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Ghany
authors.affiliation: Liver Diseases Branch, Intramural Division, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Hoofnagle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D019259:Lamivudine