HBV RNA profiles in chronic hepatitis B patients under different disease phases and anti-viral therapy.

BACKGROUND AND AIMS Large-scale comprehensive studies on hepatitis B virus (HBV) RNA in chronic hepatitis B are lacking. We aimed to study HBV RNA profile and its correlation with other viral markers in CHB treatment-naive patients and patients receiving nucleos(t)ide analogues (NA). APPROACH & RESULTS Novel biomarkers including HBV RNA and hepatitis B core-related antigen (HBcrAg) were measured in 388 patients. Of these, 246 were treatment-naive and were categorized into HBeAg-positive chronic infection (n=41), HBeAg-positive chronic hepatitis (n=81), HBeAg-negative chronic infection (n=39), HBeAg-negative chronic hepatitis (n=66), and HBsAg seroclearance (n=19). These biomarkers were also measured in 142 NA-treated patients receiving tenofovir or entecavir at baseline, week 48 and 96. The pattern of serum HBV RNA levels mirrored HBV DNA (1-2 logs higher than HBV RNA) and HBcrAg in treatment-naive patients. HBV RNA correlated best with HBcrAg (r=0.84), and to a lesser extent with HBV DNA (r=0.737) (both p 0.05). In treated-patients with undetectable HBV DNA, 77.5% and 30% had quantifiable HBV RNA and HBcrAg respectively. CONCLUSIONS HBV RNA showed distinct and corresponding profile in HBV patients in different disease phases. HBV RNA and HBcrAg could be used to monitor residual transcriptional activities in patients with HBsAg seroclearance. NA led to reduction of serum HBV RNA. Monitoring of viral activities can still be achieved in patients with undetectable HBV DNA by serum HBV RNA.