Serum Hepatitis B Virus RNA: A New Potential Biomarker for Chronic Hepatitis B Virus Infection

Abstract

Chronic hepatitis B infection is one of the major etiological causes of liver failure, cirrhosis, and hepatocellular carcinoma (HCC) worldwide. This condition cannot be completely cured by currently available drugs due to the persistent existence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), the bona fide transcription template for HBV RNAs, in infected hepatocytes. Because quantifying cccDNA per se requires an invasive procedure, serum biomarkers reflecting intrahepatic cccDNA activity are warranted. Recently, a growing body of research suggests that the circulating HBV RNA may serve as a serum biomarker for HBV infection, treatment, and prognosis. In order to delineate the molecular and clinical characteristics of serum HBV RNA, we systematically reviewed the available literature on serum HBV RNA dating back to the early 1990s. In this review, we summarize the reported serum HBV RNA quantification methods and discuss the potential HBV RNA species in patient serum. We also compare the reported correlations of serum HBV RNA with other serological markers, including HBV DNA, hepatitis B surface antigen, e antigen, and core‐related antigen, as well as their correlations with intrahepatic cccDNA, to assess their potential in clinical applications. Future directions for serum HBV RNA research are also discussed.

External validation of the modified PAGE‐B score in Asian chronic hepatitis B patients receiving antiviral therapy

“…We also recognized several unresolved issues in this study. 24,25 Lastly, the relatively high proportion (24.0%) of those treated with lamivudine in the present study might be regarded as a weakness. 26 However, provided that such patients received timely appropriate rescue therapy against virological breakthrough or resistance mutation during the periodic follow-up, the final outcome was comparable to that of those treated with ETV.…”

“…Secondly, our study was conducted based upon a single tertiary referral hospital‐based cohort, its results are potentially subject to selection bias. Thirdly, 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 . Lastly, the relatively high proportion (24.0%) of those treated with lamivudine in the present study might be regarded as a weakness .…”

Rapidly decreased HBV RNA predicts responses of pegylated interferons in HBeAg-positive patients: a longitudinal cohort study

“…Overall, our findings suggest that serum HBV RNA may serve as an early on-treatment predictor of HBV cccDNA activity to reveal the treatment success of interferon therapies. Although standard HBV RNA toolkits are yet to be developed for clinical use [7], the preliminary clinical significance of HBV RNA is supported by our large-scale study. The discovery of HBV RNA as an effective and early biomarker may lead to better management of interferon therapies for HBV-infected patients, driving the clinical use of HBV RNA [11,12,27].…”

“…Our study focused on interferon treatments in HBeAg-positive non-cirrhotic patients, while future analyses need to clarify HBV RNA in HBeAg-negative patients and associations between HBV RNA and cirrhosis or hepatocellular carcinoma. The full-length HBV RNA could be quantified using our primers taken from previous publications [12,23], but further studies need to confirm whether the encapsulated, polyadenylated serum HBV RNA is equal to full-length RNA or contains truncated RNA species [7]. Due to limited patients with HBsAg loss (2.9%) in our 72-week cohort, the associations of HBV RNA with HBsAg loss will be evaluated by our 5-year follow-up study.…”

“…HBV RNA has been recently proposed as a new biomarker to assess treatment responses, because HBV RNA transcripts produced directly from HBV cccDNA may monitor the progressive clearance of HBV cccDNA reservoirs [7][8][9]. As a potential predictor of treatment responses, serum HBV RNA is associated with intrahepatic cccDNA levels [10] and the persistence of viral infection and rebound [11].…”