title: Non-response to previous interferon therapy and cirrhosis are risk factors for predicting breakthrough during lamivudine therapy in patients with chronic hepatitis B.
abstract: OBJECTIVE
  Lamivudine is a potent oral anti-viral medicine for the treatment of hepatitis B virus (HBV) infection. However, one of the major problems is the breakthrough (BT) followed by flare-up of hepatitis. We examined the influences of clinical background, progression of liver fibrosis, presence or absence of HBeAg and previous interferon (IFN) therapy on the occurrence of breakthrough.
  
  
  METHODS
  This study comprised 51 patients with HBV related chronic hepatitis (CH) or cirrhosis (LC) who were treated with lamivudine for the mean period of 33.8 ± 13.1 months (range 3-63 months). Thirty-six patients were CH, 25 were HBeAg- positive, and 25 had a previous history of IFN therapy. Patients were divided into two groups according to the occurrence of BT, either BT(+) or BT(-). Age, gender, alanine aminotransferase (ALT) and HBV titer before treatment, normalization of ALT (≤ 40 IU/L) and flare-up of hepatitis (ALT > 80 IU/L) rates, degree of hepatic fibrosis (CH/LC), presence or absence of HBeAg (HBeAg(+)/(-), and previous IFN therapy (IFN(+)/(-) were analyzed using Cox's proportional hazards analysis.
  
  
  RESULTS
  Twenty-five patients showed BT. Background data were not different between the patients with and without BT. Flare-up of hepatitis occurred more frequently in BT. Rates of BT were markedly higher in LC (P = 0.025) and IFN(+) (P = 0.036), but HBeAg was not associated with BT. In multivariate analysis, progression of liver fibrosis (P = 0.006) and previous IFN therapy were independent risk factors for BT (P = 0.023).
  
  
  CONCLUSIONS
  BT significantly occurred in patients with LC and the history of previous IFN therapy. Multivariate analysis showed that progression of hepatic fibrosis and previous interferon therapy are independent risk factors for BT.
authors.affiliation: Digestive and Liver Disease Center, Tokai University Tokyo Hospital, 1-2-5 Yoyogi, Shibuyaku, Tokyo 151-0053, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Shiozawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishizaki
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Motegi
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Kojima
authors.forename: Norihito
authors.initials: N
authors.lastname: Watanabe
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mine
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D019259:Lamivudine; D007372:Interferons; D000410:Alanine Transaminase