HBV RNA and HBcrAg: Biomarkers of Disease Activity in CHB

Hepatitis B virus (HBV) RNA and HBcrAg (Hepatitis B core-related antigen) are both biomarkers that are used to assess disease activity in chronic hepatitis B (CHB) infection. These biomarkers can help in determining the criteria to cess NA therapy. According to the Japanese HBV guidance, the criteria to cess NA therapy are: At least 2 years of administration of NAs. Undetectable serum HBV DNA level. Negative serum HBeAg at the time of treatment cessation.

However, in case, when these criteria are met, HBsAg and HBcrAg levels can be used to estimate the risk of relapse at the time of cessation. Some of the additional points to note about HBcrAg in CHB management are:

• HBcrAg and HBV RNA offer measures of cccDNA transcriptional activity, but not the amount of cccDNA.
• Limited diagnostic application – HBcrAg is strongly influenced by HBeAg status and the presence of PC/core mutations.
• Potential prognostic applications – Prediction of hepatocellular carcinoma (HCC) risk in IND patients and after HBsAg seroclearence; prediction of HBsAg loss in a subset of patients.
• Shedding new light on HBsAg seroclearence and liver-related risk that may occur after HBsAg loss. Most likely concept that will be useful in predicting outcomes after NA withdrawal. However, the only limitations are: Need to standardization, improve dynamic range and increase access/ease of use.