Abstract
Hepatitis B virus (HBV) covalently-closed-circular (ccc)DNA is the key molecule responsible for viral persistence within infected hepatocytes. The evaluation of HBV cccDNA is crucial for the management of patients with chronic HBV infection and for the personalization of treatment. However, the need for liver biopsy is the principal obstacle for the assessment of intrahepatic HBV cccDNA. In the last decade, several studies have investigated the performance of hepatitis B core-related antigen (HBcrAg) as a surrogate of HBV cccDNA amount in the liver. In this meta-analysis, we collected 14 studies (1271 patients) investigating the correlation between serum HBcrAg and intrahepatic HBV cccDNA. Serum HBcrAg showed a high correlation with intrahepatic HBV cccDNA (r = 0.641, 95% confidence interval (CI) 0.510–0.743, p < 0.001). In a head-to-head comparison, we observed that the performance of HBcrAg was significantly superior to that of hepatitis B surface antigen (r = 0.665 vs. r = 0.475, respectively, p < 0.001). Subgroup analysis showed that the correlation between HBcrAg and intrahepatic HBV cccDNA was high, both in hepatitis B e antigen-positive and -negative patients (r = 0.678, 95% CI 0.403–0.840, p < 0.001, and r = 0.578, 95% CI 0.344–0.744, p < 0.001, respectively). In conclusion, the measurement of serum HBcrAg qualifies as a reliable non-invasive surrogate for the assessment of an intrahepatic HBV cccDNA reservoir.
Highlights
Hepatitis B virus (HBV) infection is a major health problem worldwide [1]; the estimated prevalence of HBV infected patients in the world is approximately 257 million (3.7%) [2]
We evaluated the performance of hepatitis B corerelated antigen (HBcrAg) compared to Hepatitis B surface antigen (HBsAg) as indirect markers of HBV closed-circular DNA (cccDNA), and we conducted a subgroup analysis according to hepatitis B e antigen (HBeAg)-positivity
Original research articles published in English on the correlation between serum HBcrAg and intrahepatic HBV cccDNA quantity were identified through the PubMed and Scopus databases
Summary
Hepatitis B virus (HBV) infection is a major health problem worldwide [1]; the estimated prevalence of HBV infected patients in the world is approximately 257 million (3.7%) [2]. HBV covalently-closed-circular-(ccc)DNA is the key molecule responsible for the persistence of the virus within infected hepatocytes [4], even decades after resolution of HBV infection [5]. Measuring the quantity and replication activity of HBV cccDNA is of paramount importance to improve the management of patients with CHB infection and to tailor individualized treatment strategies [7]. Exosomes derived from the serum of CHB patients were found to contain both HBV nucleic acids and HBV proteins, and could act as carriers of the virus, its nucleic acids, and proteins for further infection of uninfected hepatocytes [10].
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