On-treatment low serum HBV RNA level predicts initial virological response in chronic hepatitis B patients receiving nucleoside analogue therapy

Background: Serum HBV RNA is detectable during nucleoside/nucleotide analogue therapy as a result of unaffected RNA replicative intermediates or interrupted reverse transcription. We studied the predictive value of serum HBV RNA for initial virological response during nucleoside analogue therapy. Methods: Serum HBV RNA was quantified before and at 12 and 24 weeks of lamivudine or entecavir therapy. Serum HBV DNA was measured every 4-12 weeks during treatment to define initial virological response. Results: Serum HBV RNA was detectable in 21 of 52 (40%) consecutive patients with a mean of 5.2 log copies/ml (male/female 35/17, mean age of 60 years with a range of 31-82, 44% HBeAg-positive, and 26 with lamivudine and 26 with entecavir) before treatment. Serum HBV RNA level at week 12 in patients with an interval from detectable to undetectable serum HBV DNA level <16 weeks was significantly lower than those with an interval >= 16 weeks (3.8 +/- 3.8 versus 6.6 +/- 3.5 log copies/ml, P=0.013). After adjustment for serum HBV DNA level at week 12, serum quantatitive HBsAg level at week 12 and pretreatment ALT level, low serum HBV RNA level at week 12 predicted a shorter interval to undetectable serum HBV DNA level (adjusted hazard ratio =0.908, 95% CI 0.829, 0.993, P=0.035). Conclusions: Low serum HBV RNA level at week 12 of nucleoside analogue therapy independently predicts initial virological response in treated chronic hepatitis B patients. Serum HBV RNA levels may thus be useful for optimizing treatment of chronic hepatitis B.