Abstract
Recently, hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. This study aimed to investigate whether serum quantitative HBcrAg (qHBcrAg) was a satisfactory surrogate marker of intrahepatic covalently closed circular DNA (cccDNA). A total of 139 patients with liver biopsy were enrolled, consisting of 59 patients in immune tolerance (IT) phase, 52 patients in immune clearance (IC) phase, 18 patients in low-replication (LR) phase, and 10 patients in reactivation phase. All patients in IC phase have received entecavir (ETV) therapy, and 32 of them undergone a second liver biopsy at 24 months. Among those patients, qHBcrAg was strongly correlated with intrahepatic cccDNA, which is superior to that of qHBsAg and HBV DNA. And similar findings were also observed in patients in IT, IC, LR and reactivation phases. Among the 32 ETV-treated patients with a second liver biopsy in IC phase, the decline of intrahepatic cccDNA was accompanied by changes in both qHBcrAg and qHBsAg. However, as compared to qHBsAg, the change of qHBcrAg was more strongly associated with intrahepatic cccDNA-decline. In summary, serum qHBcrAg should be a satisfactory surrogate of intrahepatic HBV cccDNA in CHB patients.
Highlights
Chronic hepatitis B (CHB) is a potentially life-threatening liver disease caused by hepatitis B virus (HBV) chronic infection
Monitoring the dynamic changes of intrahepatic closed circular DNA (cccDNA) levels is important for accurately evaluating the effectiveness of current antiviral therapy and the risks of viral rebound resulting from discontinuation of nucleos(t)ide analogs (NAs) in CHB patients[4, 13]
Serum level of HBV DNA has been reported to correlate well with intrahepatic cccDNA levels in the natural course but not under nucleos(t)ide analogues therapy, because intrahepatic cccDNA decline did not parallel the rapid decrease of serum HBV DNA during a relative short duration of NAs therapy
Summary
Chronic hepatitis B (CHB) is a potentially life-threatening liver disease caused by hepatitis B virus (HBV) chronic infection. It remains a major global health issue affecting approximately 250 million people worldwide, especially in Asian countries[1]. In real-life clinical practice, routine liver biopsy has not been well accepted by patients, and few of them could undergo dynamic liver biopsy examinations This embarrassment of liver biopsy has brought great difficulties to the evaluation of intrahepatic HBV cccDNA levels in CHB patients. Though sustained serum HBV DNA suppression and HBeAg seroconversion are reported to be associated with disease remission[2], their efficiency in reflecting changes of intrahepatic cccDNA is poor. We will firstly investigate the distribution of serum qHBcrAg in real-life Chinese patients, assess the correlation of serum qHBcrAg with intrahepatic cccDNA, and evaluate whether serum qHBcrAg has superiority than serum qHBsAg in reflecting intrahepatic cccDNA
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