State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
Chronic hepatitis B (CHB) is one of the major etiological causes of liver failure, cirrhosis, and hepatocellular carcinoma worldwide, and it 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 the infected hepatocytes. Since quantifying cccDNA per se requires an invasive procedure, serum biomarkers reflecting the intrahepatic cccDNA activity are warranted. Recently, a growing body of research suggests that the circulating HBV RNA may serve as a new 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 early 1990s. In this review, we will summarize the reported serum HBV RNA quantification methods and discuss the potential HBV RNA species in patient serum, and compare the reported correlations of serum HBV RNA with other serological markers, including HBV DNA, hepatitis B surface antigen (HBsAg), e antigen (HBeAg), and core-related antigen (HBcrAg), as well as their correlations with the intrahepatic cccDNA, to assess its potential in clinical applications. The future directions for serum HBV RNA research will also be discussed.