Hepatitis B Virus Infection of Normal Hepatic Stem/Progenitor Cells

Whether the hepatitis B virus (HBV) infects normal hepatic stem/progenitor cells (NSCs) and if so, whether such infections play a role in the pathogenesis of HBV-induced chronic liver disease (CLD) and/or hepatocellular carcinoma (HCC) remains to be determined. The objectives of this study were to determine whether HBV infects NSCs and whether such infections alter NSC activity in a manner likely to contribute to the development of CLD and/or HCC.

Liver biopsies from five hepatitis B surface antigen (HBsAg) positive patients were co-stained for HBcAg and HBx and the stem cell markers EpCAM, Oct-4 and Nanog. In addition, primary NSCs derived from healthy human livers were exposed to HBV contaminated serum in vitro. Supernatant and/or cellular HBsAg, HBcAg and HBV-DNA expression were documented over the subsequent 30 days of culture. Pro- and anti-inflammatory cytokine expression, membrane potential differences (PDs), proliferative and telomerase activities of HBV-infected NSCs were also documented.

Markers of HBV infection were present within the NSC population of all five biopsy specimens. In vitro, HBV markers appeared within three days of exposure, peaked in expression after 10-15 days and remained positive thereafter for the duration of cell viability. There were no consistent changes in HBV-infected NSC pro- or anti-inflammatory cytokine expression, membrane PDs, proliferative or telomerase activities.

Although the results of this study need to be confirmed, they suggest that HBV infects human NSCs but in the short term, do not alter those NSC features or activities associated with CLD and/or HCC.