New Technology for Detecting Occult HBV Infection in Anti-HBc-Positive Patients

HBV test, blood test
HBV test, blood test
The livers of 100 transplant donors positive for anti-HBc were examined using an in-house droplet digital polymerase chain reaction.

A new, highly sensitive method based on droplet digital polymerase chain reaction (ddPCR) technology provides detection and quantitation of hepatitis B virus (HBV) DNA in the liver of subjects with occult HBV infection, according to a study published in the Journal of Hepatology.

Occult HBV infection is diagnosed by the presence of intrahepatic HBV covalently closed circular DNA (cccDNA) through liver biopsy. However, because occult HBV infection is asymptomatic, it is unethical to submit a healthy person to an invasive procedure; therefore, identification of antibody to the HB-core antigen (anti-HBc) in serum with standard immunoassay is considered sufficient to diagnose and treat occult HBV infection in hepatitis B surface antigen-negative persons.

Because the association between the expression and level of anti-HBc and the presence of intrahepatic HBV cccDNA remains unknown, researchers examined specimens from 100 anti-HBc-positive liver donors to determine the prevalence of occult HBV infection and the prevalence of HBV cccDNA in an occult HBV infection-positive patients.

Using a newly developed assay based on ddPCR technology, the researchers found a true occult HBV infection status in 52% of subjects, and cccDNA was found in 52% (27/52) of the occult HBV infection-positive patients. They found this method to be 10- to 100-fold more sensitive, and thus more suitable for the detection of very low concentrations of target DNA. Using an assay specific for anti-HBc of IgG class, they also found that the median antibody level was significantly higher in HBV cccDNA-positive than in cccDNA-negative donors (P=.007). In addition, multivariate analysis demonstrated that an anti-HBc IgG value above a 4.4 cutoff index was associated with intrahepatic HBV cccDNA, whereas a lower value ruled out its presence.

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The authors concluded, “With a new in-house ddPCR-based method, intrahepatic HBV cccDNA was detectable in quantifiable levels in about half of the [occult HBV infection] cases examined. The titer of anti-HBc [immunoglobulin G] may be a useful surrogate to predict the risk of [occult HBV infection] reactivation in immunosuppressed patients.”


Caviglia GP, Abate ML, Tandoi F, et al. Quantitation of HBV cccDNA in anti-HBc-positive liver donors by droplet digital PCR: a new tool to detect occult infection [published online April 2, 2018]. J Hepatol. doi: 10.1016/j.jhep.2018.03.021