Diagnostic Value of Detection of Pregenomic RNA in Sera of Hepatitis B Virus-Infected Patients with Different Clinical Outcomes

Abstract

Pregenomic RNA (pgRNA) is a direct transcription product of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), and it plays important roles in viral genome amplification and replication. This study was designed to investigate whether serum pgRNA is a strong alternative marker for reflecting HBV cccDNA levels and to analyze the correlation between serum pgRNA, serum HBV DNA, and hepatitis B surface antigen (HBsAg). A total of 400 HBV-infected patients who received nucleos(t)ide analog (NA) therapy with different clinical outcomes were involved in this research. Case groups included asymptomatic hepatitis B virus carrier (ASC), chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) patients, with 100 patients in each group. The results showed that the levels of HBV pgRNA had significant differences between these 4 groups. Serum pgRNA levels correlated well with serum HBV DNA and HBsAg levels (HBV pgRNA levels versus HBV DNA levels, r = 0.58, P < 0.001; HBV pgRNA levels versus HBsAg levels, r = 0.47, P < 0.001). In addition, we focused on the 108 HBV-infected patients with HBV DNA levels of <500 IU/ml; it was surprising to find that in 17.57% (13/74) of cases, HBV pgRNA could be detected even when the HBV DNA level was below 20 IU/ml. In conclusion, HBV pgRNA levels in serum can be a surrogate marker for intrahepatic HBV cccDNA compared with serum HBV DNA and HBsAg. The detection of serum HBV pgRNA levels may provide a reference for clinical monitoring of cccDNA levels and the selection of appropriate timing for discontinuing antiviral therapy, especially when HBV DNA levels are below the detection limit.

<p>Serum Hepatitis B Virus RNA Levels Predict HBeAg Seroconversion and Virological Response in Chronic Hepatitis B Patients with High Viral Load Treated with Nucleos(t)ide Analog</p>

“…As a new marker of hepatitis B, HBV RNA is transcribed from cccDNA and correlates equally well with intrahepatic cccDNA in CHB patients. 4,18,19 These observations suggest that the HBV RNA level can be considered a surrogate marker of the cccDNA level in infected cells.…”

Assessment of hepatitis B virus pregenomic RNA in high and low viremic chronic hepatitis B patients

“…Lin et al [23] investigated whether serum pgRNA is a strong marker that reflects HBV cccDNA values and analyzed the relation between serum pgRNA, serum HBV DNA, and HBsAg. They concluded that HBV pgRNA levels in serum can be a marker that reflects intrahepatic HBV cccDNA compared with serum HBV DNA and HBsAg.…”

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

“…Additionally, detection and measurement of liver cccDNA, considered the gold standard method for monitoring HBV replication, presents several problems. Firstly, this method requires a liver biopsy sample, which is not only invasive, but also poses several risks to the patient, such as pain, bleeding, or infection [28,29]. Secondly, cccDNA measurement methods are not standardized and include several technical obstacles, such as the possible selection of non-representative biopsy material [28,30,31].…”

“…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 ].…”