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J Clin Virol. 2013 Oct;58(2):401-7. doi: 10.1016/j.jcv.2013.08.010. Epub 2013 Aug 16.

Prediction of disease reactivation in asymptomatic hepatitis B e antigen-negative chronic hepatitis B patients using baseline serum measurements of HBsAg and HBV-DNA.

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Centre de Recherche Biomédicale Bichat-Beaujon (CRB3), INSERM U-773, Université Paris-Diderot, 92110 Clichy, France. Electronic address:


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.


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.


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.


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.


(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

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