Summary of hepatitis B virus (HBV) markers

Hepatitis B virus (HBV) infection is a worldwide epidemic. It is reported that there are about 296 million chronic HBV infected people in the world, and about 1 million people die of HBV infection related diseases every year. There is no cure for HBV infection. Only a few biomarkers can be used to monitor or predict the disease progression and treatment response of HBV infection. With the advent of new therapies, there is an urgent need for new biomarkers to monitor viral and host responses. This paper summarizes the traditional and new HBV markers, and evaluates the advantages and disadvantages of each marker.

Summary of traditional and new HBV markers: advantages and disadvantages

Quantitative detection of HBV DNA is mainly used to evaluate the level of viral replication in HBV infected people, and it is an important indicator for the selection of indications for antiviral treatment and the judgment of efficacy. However, the detection of HBV DNA is only an indirect indicator of HBV activity in the liver, which does not measure the frequency of HBV infected cells in the liver, and cannot accurately reflect the activity of HBV cccDNA. HBV DNA was quantified by real-time quantitative polymerase chain reaction, and the lower limit of detection was different according to the reagents of different manufacturers.

Serum HBsAg can be transcribed from cccDNA into mRNA for translation, or it can be transcribed and translated from HBV DNA sequence integrated into human host genome. HBsAg positive indicates HBV infection. Anti HBS is a protective antibody, and a positive one indicates HBV immunity, which is seen in the convalescent period of hepatitis B and those who have received hepatitis B vaccine.

HBsAg level is the best marker to monitor functional cure (HBsAg clearance). In some clinical settings, HBsAg level can predict HBsAg clearance or the possibility of progression to liver cancer. However, HBsAg is not suitable as a marker of immune recovery, and it is impossible to distinguish HBsAg derived from integrated HBV DNA or cccDNA. The research on the correlation between HBsAg and the possibility of liver cancer progression is limited to HBV genotypes B and C. Different genotypes or sub genotypes may express different levels of HBsAg.

In the absence of viral load detection, HBeAg quantitative detection is a surrogate indicator of HBV DNA level, and HBeAg clearance (usually accompanied by anti HBE seroconversion) is the end point of current antiviral treatment. But the clinical application of HBeAg detection is not effective for HBeAg negative chronic hepatitis B (CHB).

HBV RNA quantification is related to cccDNA transcriptional activity in hepatocytes and is an indirect indicator of cccDNA transcription. However, most detection methods cannot distinguish HBsAg or HBx RNA derived from cccDNA or integrated HBV DNA.

Hbcrag is a complex marker containing hepatitis B virus core antigen (HBcAg), HBeAg and p22cr protein. It is related to the transcriptional activity of cccDNA in hepatocytes and can accurately distinguish HBeAg negative infection from active CHB. Cohort data show that hbcrag can stratify the risk of hepatocellular carcinoma (HCC) and / or cirrhosis in patients with HBeAg negative "grey area" who receive antiviral treatment. However, it needs to be tested by highly specialized methods, and its availability is limited.

 

 

Cindy