HBV RNA Profiles in Patients With Chronic Hepatitis B Under Different Disease Phases and Antiviral Therapy

Abstract

Background and Aims Large‐scale comprehensive studies on HBV RNA in chronic hepatitis B are lacking. We aimed to study the HBV RNA profile and its correlation with other viral markers in patients with chronic hepatitis B who are treatment‐naïve and patients receiving nucleos(t)ide analogues (NA). Approach and Results Biomarkers, including HBV RNA and hepatitis B core‐related antigen (HBcrAg), were measured in 388 patients. Of these, 246 were treatment‐naïve 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 patients who were NA‐treated receiving tenofovir or entecavir at baseline, week 48, and week 96. The pattern of serum HBV RNA levels mirrored HBV DNA (1‐2 logs higher than HBV RNA) and HBcrAg in patients who were treatment‐naïve. HBV RNA correlated best with HBcrAg (r = 0.84) and to a lesser extent with HBV DNA (r = 0.737) (both P < 0.001). In patients with HBsAg seroclearance, 15.8% and 15.8% had detectable serum HBV RNA and HBcrAg, respectively. NA treatment reduced serum HBV RNA by 1.46 logs and 1.77 logs at weeks 48 and 96, respectively. At week 96 of NA therapy, only 19.1% patients who were tenofovir‐treated and 25.7% patients who were entecavir‐treated had unquantifiable HBV RNA (P > 0.05). In patients who were treated and had undetectable HBV DNA, 77.5% and 30% had quantifiable HBV RNA and HBcrAg, respectively. Conclusions HBV RNA showed distinct and corresponding profiles in patients with HBV 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.

External validation of CAGE‐B and SAGE‐B scores for Asian chronic hepatitis B patients with well‐controlled viremia by antivirals

“…Second, our study was conducted based upon the tertiary referral hospital‐based cohort, and its results are potentially subject to selection bias. Third, the use of new biomarkers (eg serum quantitative HBsAg, serum hepatitis B core–related antigen, serum HBV RNA or specific HBV mutants), which can reflect the clinical course of CHB, would have provided the more precise prediction 52–57 …”

Novel Biomarkers of Hepatitis B Virus and Their Use in Chronic Hepatitis B Patient Management

“…Many studies have evaluated the correlation between HBV RNA and other traditional or novel HBV biomarkers to investigate HBV natural history and determine the utility of serum HBV RNA as an alternative biomarker. In treatment-naïve patients within multi-ethnic cohorts, it has been shown that levels of serum HBV RNA are higher in HBeAg-positive CHB patients than in those who are HBeAg-negative [ 22 , 29 , 39 , 40 , 41 ]. Additionally, a strong correlation between serum HBV DNA and serum HBV RNA levels in treated and untreated patients has been reported [ 22 , 32 , 40 , 42 ].…”

“…Additionally, a strong correlation between serum HBV DNA and serum HBV RNA levels in treated and untreated patients has been reported [ 22 , 32 , 40 , 42 ]. However, this correlation has not been consistently observed in treatment-naïve patients [ 39 , 43 ]. Serum HBV RNA was also found to correlate with HBcrAg [ 39 ] and moderately correlate with HBsAg and HBeAg quantities [ 40 ] in treatment-naïve patients.…”

Is there any need for new, long-acting nucleos(t)ide analogues for the treatment of hepatitis B infection?

“…maintenance of viremia) or to maintain the level of cccDNA following recycling of rcDNA to the nucleus, 9 careful/close monitoring of viremia using very potent qPCR technology has demonstrated partial virologic responses in longterm NA-treated patients, with viremia varying between "non detectable" and very low levels. 10 This indicates that the blockade of HBV Pol activity is not 100%. This also has consequences for cccDNA levels, as residual HBV Pol activity might be sufficient to maintain the cccDNA pool.…”