Background: The natural history of HBV infection includes immune tolerance (IT), immune clearance (IC), HBeAg-negative inactive/quiescent carrier (ENQ), and HBeAg-negative hepatitis (ENH) phases. As the current biomarkers for discriminating the four phases still have some weaknesses, additional serological indicators are needed. Hepatitis B core-related antigen (HBcrAg) encoded with the precore/core gene contains denatured HBeAg, HBV core antigen (HBcAg), and a 22-KDa precore protein (p22cr) and has been demonstrated to have a close association with the natural history of hepatitis B infection. However, no specific cutoff values and diagnostic parameters have been identified to evaluate the diagnostic efficacy. This study aimed to clarify the distribution of HBcrAg levels and evaluate the diagnostic performance during the natural history of HBV infection in a Western Chinese population.
Methods: In this study, 294 samples were collected from treatment-naive HBV infection patients in different phases (IT = 64; IC = 72; ENQ = 100, and ENH = 58). We detected the HBcrAg values and analyzed the relationship between HBcrAg and HBV DNA. HBsAg and other clinical parameters were quantitatively detected.
Results: The HBcrAg levels of IT, IC, ENQ, and ENH were 9.30 log U/mL, 8.80 log U/mL, 3.00 log U/mL, and 5.10 log U/mL, respectively (p < 0.0001). Receiver operating characteristic curve analysis demonstrated that the areas under the curves (AUCs) for HBcrAg and quantitative HBsAg at cutoff values of 9.25 log U/mL and 4.355 log IU/mL for distinguishing the IT phase from the IC phase were 0.704 and 0.694, with a sensitivity of 53.13% and 79.69% and specificity of 76.39% and 59.72%, respectively. AUCs of HBcrAg and quantitative HBsAg at cutoff values of 4.15 log U/mL and 2.395 log IU/mL for discriminating between the ENQ and ENH phases were 0.931 and 0.653, with a sensitivity of 87.93% and 91.38% and specificity of 84.00% and 39.00%, respectively.
Conclusions: HBcrAg levels varied significantly among the four natural phases of HBV infection and had higher predictive performance than quantitative HBsAg for distinguishing between ENQ-patients and ENH-patients and a similar performance as HBsAg for the discrimination between IT and IC phases, which indicated that HBcrAg could be a potential serological marker for HBV infection.