Clinical Implications of Serum Hepatitis B Virus Pregenomic RNA Kinetics in Chronic Hepatitis B Patients Receiving Antiviral Treatment and Those Achieving HBsAg Loss

Abstract

Serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) is correlated with covalently closed circular DNA. We aimed to investigate the utility of serum HBV pgRNA in chronic hepatitis B patients receiving nucleos(t)ide analogue treatment and those achieving HBsAg loss. One hundred and eighty-five patients were enrolled for studying long-term HBV pgRNA kinetics during treatment. Twenty patients achieving HBsAg loss after treatment were enrolled for examining HBV pgRNA kinetics around HBsAg loss. HBV pgRNA significantly decreased in the high baseline HBV pgRNA (≥6 log copies/mL) group but significantly increased in the low baseline HBV pgRNA (<4 log copies/mL) group after 3-month entecavir treatment. Among the 20 patients achieving HBsAg loss, 13 (65%) patients had serum HBV pgRNA higher than the limit of detection (LOD, 1466 copies/mL) when they achieved HBsAg loss. Finally, all 20 patients had HBV pgRNA going below the LOD within 3 years after achieving HBsAg loss. In conclusion, baseline serum HBV pgRNA alone is insufficient for predicting the trajectory of HBV pgRNA. Most patients still had HBV pgRNA higher than the LOD when they achieved HBsAg loss. Further studies on HBV pgRNA kinetics around HBsAg loss would provide an enhanced basis for further applications of HBV pgRNA.

Dynamics of Hepatitis B Virus Pregenomic RNA in Chronic Hepatitis B Patients With Antiviral Therapy Over 9 Years

“…Regarding the turning time of HBsAg and HBV pgRNA, all HBV pgRNA disappeared before or at HBsAg loss, with a lower LOD of HBV pgRNA. However, Wu et al reported that 65% of patients with HBV pgRNA had a later negative turning than HBsAg (11).…”

“…After 9-year NA treatment, 9.9% of the patients still had detectable serum HBV pgRNA levels. Wu et al (11) reported that baseline serum HBV pgRNA alone was not sufficient to predict the trajectory of HBV pgRNA. Similarly, clinical characteristics were not significantly different between patients positive and negative for HBV pgRNA at the early stage of therapy.…”

Impact of HCV viremia on HBV biomarkers in patients coinfected with HBV and HCV

“…HBV RNA was extracted from 150 µL of serum using the Total RNA Extraction Miniprep System Kit according to the manufacturer’s instructions (Viogene, Taipei, Taiwan) and treated with DNase I (Thermo Fisher Scientific, Waltham, MA, USA). Isolated HBV RNA was reverse transcribed to complementary DNA using RevertAid reverse transcriptase (Thermo Fisher Scientific, Waltham, MA, USA) with an HBV specific RT primer for HBV pgRNA [ 24 ]. The complementary DNA samples were held at 4 °C before proceeding to quantitative real-time polymerase chain reaction.…”

“…The levels of serum HBV RNA were detected by qPCR in LightCycler 480 II Real-time PCR Detection System (Roche, Mannheim, Germany) with a SYBR Green method [ 24 ]. The limit of detection of serum HBV pgRNA was 1466 copies/mL, as calculated by probit analysis [ 24 ].…”

“…The levels of serum HBV RNA were detected by qPCR in LightCycler 480 II Real-time PCR Detection System (Roche, Mannheim, Germany) with a SYBR Green method [ 24 ]. The limit of detection of serum HBV pgRNA was 1466 copies/mL, as calculated by probit analysis [ 24 ]. For statistical analysis, those serum samples with HBV pgRNA below limit of detection or not detected were recorded as 1465 copies/mL (3.17 log copies/mL).…”