title: Prediction of disease reactivation in asymptomatic hepatitis B e antigen-negative chronic hepatitis B patients using baseline serum measurements of HBsAg and HBV-DNA.
abstract: Differentiating 'inactive carriers' (ICs) of hepatitis B virus (HBV) from hepatitis B e antigen-negative (HBeAg[-]) patients in remission is challenging. We investigated whether serum-based monitoring of hepatitis B surface antigen (HBsAg) and HBV-DNA in asymptomatic HBeAg(-) patients could distinguish these groups.
  
  
  METHODS
  129 HBeAg(-) chronic hepatitis B (CHB) patients (HBV genotypes A-E) with normal alanine aminotransferase (ALT) levels at baseline were classified after 1 year of follow-up as either IC (HBV-DNA ≤2000 IU/mL) or 'active carrier' (AC, HBV-DNA >2000 IU/mL) if they exhibited normal ALT throughout, or classified as 'reactivation patient' (RP) if they exhibited marked, transient increases in ALT and HBV-DNA.
  
  
  RESULTS
  There were 64%, 18%, and 19% patients in the IC, AC, and RP groups, respectively. Combined HBsAg and HBV-DNA cutoffs (>1000 IU/mL and >200 IU/mL, respectively) differentiated RPs with 92% sensitivity and negative predictive value (NPV) of 96%. HBsAg sero-clearance was associated with baseline HBsAg <1000 IU/mL, annual decrease of ≥0.3 log IU/mL (NPV 95%: PPV 89%) and IFNL3 genotype CC.
  
  
  CONCLUSIONS
  Applying combined HBsAg and HBV-DNA cutoffs to baseline measurements accurately differentiated RPs. These results suggest that HBsAg should be included in the monitoring of asymptomatic HBeAg(-) CHB patients.
authors.affiliation: Centre de Recherche Biomédicale Bichat-Beaujon (CRB3), INSERM U-773, Université Paris-Diderot, 92110 Clichy, France. Electronic address: michelle.martinot@inserm.fr.
authors.forename: Michelle
authors.initials: M
authors.lastname: Martinot-Peignoux
authors.forename: Martine
authors.initials: M
authors.lastname: Lapalus
authors.forename: Cédric
authors.initials: C
authors.lastname: Laouénan
authors.forename: Olivier
authors.initials: O
authors.lastname: Lada
authors.forename: Ana Carolina Ferreira
authors.initials: AC
authors.lastname: Netto-Cardoso
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boyer
authors.forename: Marie Pierre
authors.initials: MP
authors.lastname: Ripault
authors.forename: Roberto
authors.initials: R
authors.lastname: Carvalho-Filho
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
mesh_terms: D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000097:blood; D002353:Carrier State / Q000453:epidemiology / Q000821:virology; D004247:DNA; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000453:epidemiology* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D044967:Serum / Q000821:virology*; D014775:Virus Activation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D004247:DNA; D000410:Alanine Transaminase
keywords: (previous IL28B); AC; ALT; BCP; CHB; HBV; HBV inactive carrier; HBV-DNA; HBeAg; HBsAg; HCC; IC; IFN; IFNL3; NPV; PC; PPV; Prognosis; RP; Viral hepatitis; active carrier; alanine aminotransferase; basal core promoter; chronic hepatitis B; hepatitis B e antigen; hepatitis B surface antigen; hepatitis B virus; hepatocellular carcinoma; inactive carrier; interferon; negative predictive value; positive predictive value; precore; reactivation patient