Latent HBV Liver Infection

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Researchers Claim that "Latent" HBV Liver Infection is Common Even Without Positive Blood Antigen Tests



By Harvey S. Bartnof, MD



Previously, patients with a positive HBV (* hepatitis B virus) core antibody test and a negative surface antigen test indicated past or resolved HBV infection. Yet, it has been observed that some liver transplant recipients developed acute HBV infection even when the donor was negative for surface antigen and positive for core antibody. Now, researchers from Kyoto University in Japan have detected HBV DNA in liver samples from 24 of 32 healthy, related liver donors with negative tests for HBV antigens and genomes in blood and normal ALT ** tests, yet with a positive antibody test to HBV core. (** ALT is alanine aminotransferase, liver enzyme) The presence of HBV antigens or HBV DNA would suggest active replication (active infection) or the potential for replication, respectively. The report was presented at Digestive Disease Week 2000 that was held in San Diego, California between May 21-24, 2000.



Liver samples were tested by RT-PCR (reverse transcriptase-polymerase chain reaction) and by "amplification" of DNA to detect "ccc" ("covalently" closed circular) HBV DNA. The results showed that 66% of the 32 healthy donors had detectable HBV DNA in liver, including ccc DNA and "pregenomic" RNA, a replication intermediate. Positive antibody tests to HBV core and surface and/or antibodies to "e" (antigen) were "closely correlated with the presence of HBV genome in the liver tissue." All 32 donors had negative tests for HBV antigens and viral genomes (DNA) in blood serum (no cells) and normal liver enzymes. When seven of the donors were tested for HBV mutations, five of them predominantly had "wild type," without any detected "core" or "pre-core" mutations.



The authors concluded, "the majority of healthy individuals positive for anti-HBc [antibody to hepatitis B core] but negative for HBsAg [hepatitis B surface antigen], which had been assumed to denote a past history of transient HBV infection, were latently infected with the episomal form of HBV accompanied with ongoing viral replication and few nucleotide mutations in the pre-core and core regions."



Whether those donors would be susceptible to "reactivation" of hepatitis B with developing clinical disease is not known, but is likely to be uncommon without reasons for immune suppression, including HIV. Without active HBV replication in blood, transmission to needle/works-sharing partners would seem unlikely. Whether such individuals might transmit HBV to sexual partners would require testing for HBV DNA or antigens in semen and vaginal/cervical fluids. However, the transplant recipients are treated with immune altering medications to prevent liver graft rejection by the recipient's immune system. In that situation, the recipients can develop active HBV infection. Yet, recipients receive HBIG (hepatitis B immune globulin) and sometimes hepatitis B vaccine that can prevent active infection.



The authors of this poster received a "DDW Poster of Distinction" award.



References



Marusawa H and others. Molecular mechanisms of latent hepatitis B virus infection in anti-HBc positive healthy individuals without HBsAg. Abstract 171 at Digestive Disease Week 2000; May 21-24, 2000; San Diego, California.