Background:    Chronic hepatitis B, HBeAg negative infection with inactive HBV DNA can become active during follow up. Previous studies have demonstrated that male, younger age and higher HBV virus at entry are among predictors of subsequent virological flare. There are studies demonstrated that quantitative HBsAg (qHBsAg) correlated with cccDNA and might predict HBV DNA flare.

Objective: This study was aimed to determine whether qHBsAg and/or HBV DNA can predict HBV DNA flare.

Materials and Methods: This is a prospective study includes inactive chronic hepatitis B patients naïve to treatment with HBV DNA < 2,000 IU/mL at hepatitis clinic, Siriraj Hospital from May1, 2008 to December 31, 2009. The patients were followed every 6 months with ALT, HBV DNA viral load and qHBsAg to evaluate virological flare at 1 year of follow-up.

Results: There were91 patients (49 male, 42 female), mean age of 50 years old with mean follow up time of 308 days. Baseline mean HBV DNA, qHBsAg and ALT were 364 IU/ml (range 6-1930), 2831 IU/mL (range 0.15-23794) and 28 U/L (range 8-78), respectively. At last follow-up, the mean values of HBV DNA, qHBsAg, and ALT were 1310 IU/ml (range 6-51500), 2239 IU/mL (range 0.04-29242) and 26 U/L (range 9-88), respectively. Twenty-one of 91 patients (23%) had virological flare at 1 year of follow-up. There no correlation of qHBsAg and HBV DNA over the time (r=0.25 (p<.001). The only predictor of virological flare was the higher baseline DNA (p<0.001). Overall, HBsAg level was not the predictor of virological flare, however, when we analyzed the patients with initial HBsAg level < 250 IU/mL we found that this level can predict absent of virological flare with the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of  76.2, 55.7, 34.0, and 88.6%, respectively, with AUC of 0. 66 (95%CI,0.54-0.77, p = 0.03). qHBsAg combined with HBV DNA below detection limit even offered better predictive values with sensitivity, specificity, PPV and NPV of 100, 23, 28, and 100%, respectively (p = 0.018). Those with virological flare, the only predictor of sustained virological flare was high baseline ALT.

Conclusions: Inactive chronic hepatitis B can have virological flare 23% in 1 year. Our study has found poor correlation between qHBsAg and HBV DNA. However, low baseline HBV DNA together with low qHBsAg level (<250 IU/mL) is useful to predict the absent of subsequent virological flare in inactive CHB patients. However, more data with more patients and longer follow-up period is needed to confirm this finding.

Key words: qHBsAg, HBV DNA, predicting factors of HBV flare