title: Outcome of hepatitis B e antigen-negative chronic hepatitis B on long-term nucleos(t)ide analog therapy starting with lamivudine.
abstract: We determined the clinical outcome of hepatitis e antigen (HBeAg)-negative chronic hepatitis B patients treated with long-term nucleos(t)ide analog therapy starting with lamivudine. We evaluated 201 such patients treated for 3.8 +/- 1.4 years and 2 historical similar cohorts: 1 treated with interferon-alfa (n = 209) and 1 untreated (n = 195). Virological or biochemical remission rate at 48 months under lamivudine was 34% or 36%, respectively, whereas adefovir was administered in 79 patients with virological-biochemical breakthroughs or no response. Of the lamivudine-treated patients, 4 died, 1 underwent a transplantation, and another 8 developed major events, all having advanced fibrosis at baseline and all but 1 having experienced breakthroughs or no response. At 5 years, survival was 96%, and major event-free survival was 93%. The major event-free survival was significantly better in patients with than in those without virological remission under lamivudine. At the end of follow-up, both survival and major event-free survival were independently associated with type of and response to treatment, being significantly better in patients under long-term antiviral therapy or interferon sustained responders than in interferon non-sustained responders or untreated cases (5-year survival: 96% or 98% vs. 88% or 90%, respectively). In conclusion, in HBeAg-negative chronic hepatitis B, long-term nucleos(t)ide analog therapy starting with lamivudine significantly improves survival and reduces the risk of major complications, compared with interferon non-sustained responders or untreated patients. In such patients with advanced fibrosis, close follow-up for lamivudine resistance and prompt onset of additional antiviral therapy is required or the ab initio use of agent(s) with low resistance rates should be considered.
authors.affiliation: 2nd Academic Department of Internal Medicine, Hippokration General Hospital of Athens, Greece.
authors.forename: George V
authors.initials: GV
authors.lastname: Papatheodoridis
authors.forename: Evangelini
authors.initials: E
authors.lastname: Dimou
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Dimakopoulos
authors.forename: Spilios
authors.initials: S
authors.lastname: Manolakopoulos
authors.forename: Irene
authors.initials: I
authors.lastname: Rapti
authors.forename: George
authors.initials: G
authors.lastname: Kitis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tzourmakliotis
authors.forename: Emanuel
authors.initials: E
authors.lastname: Manesis
authors.forename: Stephanos J
authors.initials: SJ
authors.lastname: Hadziyannis
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D005260:Female; D006513:Hepatitis B e Antigens / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use*; D017093:Liver Failure / Q000209:etiology; D008113:Liver Neoplasms / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000819:agonists; D009711:Nucleotides / Q000819:agonists; D063065:Organophosphonates / Q000627:therapeutic use; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D009705:Nucleosides; D009711:Nucleotides; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000225:Adenine