Clonal expansion of hepatocytes with a selective advantage occurs during all stages of chronic hepatitis B virus infection

Tu, T, Mason, W.S, Clouston, A.D, Shackel, N.A, Mccaughan, G.W, Yeh, M.M, Schiff, E.R, Ruszkiewicz, A.R, Chen, J.W, Harley, H.A.J, Stroeher, U.H and Jilbert, A.R (2015) Clonal expansion of hepatocytes with a selective advantage occurs during all stages of chronic hepatitis B virus infection. Journal of Viral Hepatitis, 22 9: 737-753. doi:10.1111/jvh.12380


Author Tu, T
Mason, W.S
Clouston, A.D
Shackel, N.A
Mccaughan, G.W
Yeh, M.M
Schiff, E.R
Ruszkiewicz, A.R
Chen, J.W
Harley, H.A.J
Stroeher, U.H
Jilbert, A.R
Title Clonal expansion of hepatocytes with a selective advantage occurs during all stages of chronic hepatitis B virus infection
Journal name Journal of Viral Hepatitis   Check publisher's open access policy
ISSN 1365-2893
1352-0504
Publication date 2015-01-26
Year available 2015
Sub-type Article (original research)
DOI 10.1111/jvh.12380
Volume 22
Issue 9
Start page 737
End page 753
Total pages 17
Place of publication Chichester, United Kingdom
Publisher Blackwell Publishing Ltd
Collection year 2016
Language eng
Abstract Hepatocyte clone size was measured in liver samples of 21 patients in various stages of chronic hepatitis B virus (HBV) infection and from 21 to 76 years of age. Hepatocyte clones containing unique virus–cell DNA junctions formed by the integration of HBV DNA were detected using inverse nested PCR. The maximum hepatocyte clone size tended to increase with age, although there was considerable patient-to-patient variation in each age group. There was an upward trend in maximum clone size with increasing fibrosis, inflammatory activity and with seroconversion from HBV e-antigen (HBeAg)-positive to HBeAg-negative, but these differences did not reach statistical significance. Maximum hepatocyte clone size did not differ between patients with and without a coexisting hepatocellular carcinoma. Thus, large hepatocyte clones containing integrated HBV DNA were detected during all stages of chronic HBV infection. Using laser microdissection, no significant difference in clone size was observed between foci of HBV surface antigen (HBsAg)-positive and HBsAg-negative hepatocytes, suggesting that expression of HBsAg is not a significant factor in clonal expansion. Laser microdissection also revealed that hepatocytes with normal-appearing histology make up a major fraction of the cells undergoing clonal expansion. Thus, preneoplasia does not appear to be a factor in the clonal expansion detected in our assays. Computer simulations suggest that the large hepatocyte clones are not produced by random hepatocyte turnover but have an as-yet-unknown selective advantage that drives increased clonal expansion in the HBV-infected liver.
Keyword Clonal expansion of hepatocytes
Hepatitis B virus
Hepatocellular carcinoma
Inverse nested PCR
Laser microdissection
Virus-cell DNA junction
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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