Viral Hepatitis
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2005; 11(41): 6416-6421
Published online Nov 7, 2005. doi: 10.3748/wjg.v11.i41.6416
Integration of hepatitis B virus DNA into chromosomal DNA during acute hepatitis B
Gerald C Kimbi, Anna Kramvis, Michael C Kew
Gerald C Kimbi, Anna Kramvis, Michael C Kew, MRC/University Molecular Hepatology Research Unit, Department of Medicine, University of the Witwatersrand, Parktown 2193, Johannesburg, South Africa
Author contributions: All authors contributed equally to the work.
Supported by grants from the Poliomyelitis Research Foundation of South African and the HE Griffin Cancer Trust
Correspondence to: Professor, MC Kew, Department of Medicine, University of the Witwatersrand Medical School, 7 York Road, Parktown 2193, Johannesburg, South Africa. kewmc@medicine.wits.ac.za
Telephone: +27-11-488-3628 Fax: +27-11-643-4318
Received: August 26, 2004
Revised: October 2, 2004
Accepted: October 6, 2004
Published online: November 7, 2005
Abstract

AIM: To examine the serum from black African patients with acute hepatitis B to ascertain if integrants of viral DNA can be detected in fragments of cellular DNA leaking from damaged hepatocytes into the circulation.

METHODS: DNA was extracted from the sera of five patients with uncomplicated acute hepatitis B and one with fulminant disease. Two subgenomic PCRs designed to amplify the complete genome of HBV were used and the resulting amplicons were cloned and sequenced.

RESULTS: HBV and chromosomal DNA were amplified from the sera of all the patients. In one patient with uncomplicated disease, HBV DNA was integrated into host chromosome 7 q11.23 in the WBSCR1 gene. The viral DNA comprised 200 nucleotides covering the S and X genes in opposite orientation, with a 1 169 nucleotide deletion. The right virus/host junction was situated at nucleotide 1 774 in the cohesive overlap region of the viral genome, at a preferred topoisomerase I cleavage motif. The chromosomal DNA was not rearranged. The patient made a full recovery and seroconverted to anti-HBs- and anti-HBe-positivity. Neither HBV nor chromosomal DNA could be amplified from his serum at that time.

CONCLUSION: Integration of viral DNA into chromosomal DNA may occur rarely during acute hepatitis B and, with clonal propagation of the integrant, might play a role in hepatocarcinogenesis.

Keywords: Hepatocellular; Chronic hepatitis B infection; Clonal propagation