Hepatitis B virus persistence after recovery from acute viral hepatitis.

Abstract

Contrary to current opinion, the disappearance of hepatitis B surface antigen (HBsAg) from the serum, the development of anti-HBs antibodies, and normalization of liver function may not reflect complete virological recovery from acute hepatitis B virus (HBV) infection. By using the polymerase chain reaction (PCR), in the current study we demonstrate long-term persistence of HBV DNA in the serum and peripheral blood mononuclear cells (PBMC) of four patients for up to 70 mo after complete clinical, biochemical, and serological recovery from acute viral hepatitis. Serum HBV DNA reactivity co-sedimented with HBsAg in sucrose gradients, and it displayed the size and density characteristics of naked core particles and intact HBV virions, presumably contained within circulating immune complexes in these anti-HBs antibody-positive sera. HBV DNA was also present in PBMC in late convalescent samples from all four patients, and HBV RNA was detected in late convalescent phase PBMC in two of these patients. These results suggest that HBV DNA, and possibly HBV virions, can be present in the serum, and that the viral genome can persist in a transcriptionally active form in PBMC for > 5 yr after complete clinical and serological recovery from acute viral hepatitis. (J.

Hepatitis B Virus and Renal Transplantation

“…Numerous observations have suggested that HBV DNA can be present in the serum and/or liver of healthy individuals long after complete clinical and serologic recovery from acute hepatitis B infection [33, 34]. Rehermann et al [17]have noted HBV DNA in plasma and circulating lymphocytes of patients up to 23 years after resolution of HBV infection.…”

Clinical Significance of Occult Hepatitis B Infection in Progression of Liver Disease and Carcinogenesis

“…During the natural history of chronic hepatitis B, seroconversion from HBsAg to anti-HB surface antibody (anti-HBs) is related to the remission of active hepatitis and improvement of liver function and pathological features. Individuals who have recovered from acute hepatitis B or those who have lost serum HBsAg during their clinical course might carry HBV genomes for several years without presenting any clinical evidence of chronic liver disease 5-7…”

Minicircle HBV cccDNA with a Gaussia luciferase reporter for investigating HBV cccDNA biology and developing cccDNA-targeting drugs

“…4b), in contrast to non-HBV minicircle DNA or control plasmid HBV genomic DNA. It has been reported that HBV cccDNA persists stably in chronic infected patients through unknown mechanism(s) even when virus replication is effectively suppressed for decades1114151617. HBV cccDNA can also be maintained in HBV-infected HepaRG cells for several weeks24.…”

“…Reports based on studying the Duck Hepatitis Virus (DHBV) show that cccDNA binds nucleosome proteins and forms a minichromosome12, which can be stably maintained in nondividing hepatocytes during treatment as an episomal DNA13. The HBV viral rebound was observed even after decades of successful HBV suppression associated with robust anti-HBV immune response after acute infection14151617 or after IFNα treatment11, indicating that episome cccDNA can persist stably in an occult status. As minichromosomes, cccDNA has been identified to be associated with histone proteins and its function is regulated by epigenetic “writers”, “readers” and “erasers”181920212223.…”