title: Durability of serologic response after lamivudine treatment of chronic hepatitis B.
abstract: Forty subjects with chronic hepatitis B and hepatitis B e antigen (HBeAg) seroconversion following lamivudine therapy in previous trials were monitored after treatment to assess the durability of serologic responses. Patient follow-up began a median of 4.3 months after completion of therapy in previous trials. At months 2, 4, 6, 9, and 12 of year 1, and every 6 months thereafter, we tested for HBeAg and hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV) DNA, and alanine aminotransferase (ALT). After a median (range) of 36.6 (4.8-45.6) months of follow-up monitoring, HBeAg seroconversion was demonstrated at the last visit by 77% (30 of 39) of patients. In a post hoc analysis of a slightly different population of all 65 patients with HBeAg seroconversion in previous trials, the 3-year durability of HBeAg seroconversion measured from the time immediately after discontinuing lamivudine therapy was 64%. Nine (9 of 40, 23%) patients were HBsAg negative at the last assessment. Seventy-four percent (17 of 23) of patients with baseline undetectable HBV DNA and normal ALT maintained these responses at the last visit. Eight patients (8 of 40, 20%) initiated retreatment for reappearance of HBV markers, and 7 showed biochemical and/or virologic improvement (including regained HBeAg seroconversion in 2). No safety issues of concern emerged. In conclusion, most HBeAg responses achieved during lamivudine therapy were durable, and most responders experienced prolonged clinical benefit after HBeAg seroconversion and subsequent discontinuation of lamivudine. Lamivudine retreatment for reappearance of hepatitis B markers can achieve resumption of viral suppression.
authors.affiliation: Gastrointestinal Unit (Medical Services), Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA. jdienstag@partners.org
authors.forename: Jules L
authors.initials: JL
authors.lastname: Dienstag
authors.forename: Janusz
authors.initials: J
authors.lastname: Cianciara
authors.forename: Selim
authors.initials: S
authors.lastname: Karayalcin
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
authors.forename: Bernard
authors.initials: B
authors.lastname: Willems
authors.forename: Stanilav
authors.initials: S
authors.lastname: Plisek
authors.forename: Mary
authors.initials: M
authors.lastname: Woessner
authors.forename: Stephen
authors.initials: S
authors.lastname: Gardner
authors.forename: Eugene
authors.initials: E
authors.lastname: Schiff
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D004279:DNA, Viral / Q000378:metabolism; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000032:analysis*; D006513:Hepatitis B e Antigens / Q000032:analysis*; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019233:Retreatment; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012449:Safety; D013997:Time Factors
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000410:Alanine Transaminase