Hepatitis B core-related antigen (HBcrAg) levels in the natural history of hepatitis B virus infection in a large European cohort predominantly infected with genotypes A and D

Abstract

Hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. HBcrAg combines the antigenic reactivity resulting from denatured hepatitis B e antigen (HBeAg), HBV core antigen and an artificial core-related protein (p22cr). In Asian patients, high levels of HBcrAg have been suggested to be an independent risk factor for hepatocellular carcinoma, while low levels could guide safe cessation of treatment with nucleos(t)ide analogues. We here studied HBcrAg levels in different phases of HBV infection in a large European cohort predominantly infected with genotypes A and D: HBeAg-positive immune tolerance (n = 30), HBeAg-positive immune clearance (IC) (n = 60), HBeAg-negative hepatitis (ENH) (n = 50), HBeAg-negative inactive/quiescent carrier phase (c) (n = 109) and acute hepatitis B (n = 8). Median HBcrAg levels were high in the immune tolerance and immune clearance phases (8.41 and 8.11 log U/mL, respectively), lower in ENH subjects (4.82 log U/mL) but only 2.00 log U/mL in ENQ subjects. Correlation between HBcrAg and HBV DNA varied among the different phases of HBV infection, while HBcrAg moderately correlated with hepatitis B surface antigen in all phases. ENQ patients had HBcrAg levels <3 log U/mL in 79%, in contrast to only 12% in the ENH group. HBcrAg levels vary significantly during the different phases of HBV infection. HBcrAg may serve as valuable marker for virus replication and reflect the transcriptional activity of intrahepatic cccDNA. In HBeAg-negative patients, HBcrAg may help to distinguish between inactive carriers (ENQ) and those with active disease (ENH).

Complete and Incomplete Hepatitis B Virus Particles: Formation, Function, and Application

“…This aberrant protein was also named HBcrAg. In the literature, the term “HBcrAg” has been used to describe a combination of HBc and HBe [13,86,87,88]; the supposedly aberrant p22cr [47]; and a combination of all three entities, HBc, HBe, and p22cr [89,90,91]. As discussed above, the so-called p22cr probably does not really exist and the current HBcrAg ELISA kit most likely detects a combination of HBcAg (released from virions) and HBeAg.…”

“…Not surprisingly, serum HBcrAg levels were found to correlate relatively well with serum HBV DNA and HBsAg levels, to decrease in HBeAg (−) phase, and to decrease much slower than serum HBV DNA and remains detectable in serum HBV DNA (−) patients upon nucleoside reverse transcriptase inhibitor (NRTI) treatment [13,88,90], as we observed for serum empty virions [9]. Furthermore, serum HBcrAg levels were correlated with CCC DNA levels and frequency of HBcAg (+) hepatocytes in the liver and with liver disease activity [87,89,92,93].…”

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

“…228,229 It might also be helpful in defining the phase of chronic HBV infection, especially in HBenegative patients, as well as predicting the long-term HCC risk. 228,[230][231][232] Some studies suggest that this biomarker can be also used to monitor NA or PegIFNa based treatments and predicting therapeutic efficacy including the risk of relapse after stopping NAs. [233][234][235] Most of these studies were performed in Japan, and large correlation studies derived from Caucasian patients are lacking.…”

Hepatitis C virus infection in children and adolescents

“…In adults, more rapid disease progression has been shown to be affected by viral load, serum aminotransferase levels, gender, ethnicity, obesity, toxins, and other environmental factors. Comorbidities, including hemolytic anemia, malignancy, immunosuppression, HIV, and hepatitis B virus (HBV) co‐infection and certain genetic factors, like single‐nucleotide polymorphisms, may also promote progression 83. Similarly, children with comorbid conditions, such as obesity, HIV, and HBV co‐infections, cancer, and anemia, are at risk for more severe disease 4, 84.…”