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. Design129 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 ≤2000IU/mL) or ‘active carrier’ (AC, HBV-DNA >2000IU/mL) if they exhibited normal ALT throughout, or classified as ‘reactivation patient’ (RP) if they exhibited marked, transient increases in ALT and HBV-DNA. ResultsThere were 64%, 18%, and 19% patients in the IC, AC, and RP groups, respectively. Combined HBsAg and HBV-DNA cutoffs (>1000IU/mL and >200IU/mL, respectively) differentiated RPs with 92% sensitivity and negative predictive value (NPV) of 96%. HBsAg sero-clearance was associated with baseline HBsAg <1000IU/mL, annual decrease of ≥0.3logIU/mL (NPV 95%: PPV 89%) and IFNL3 genotype CC. ConclusionApplying 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.