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Integration of hepatitis B virus DNA in chronically infected patients assessed by Alu-PCR

Journal article
Authors Simon B. Larsson
Gianluca Tripodi
G. Raimondo
C. Saitta
Gunnar Norkrans
T. Pollicino
Magnus Lindh
Published in Journal of Medical Virology
Volume 90
Issue 10
Pages 1568-1575
ISSN 0146-6615
Publication year 2018
Published at Institute of Biomedicine, Department of Infectious Medicine
Pages 1568-1575
Language en
Keywords Alu-PCR, hepatocellular carcinoma (HCC), hepatitis B virus (HBV), integration, intrahepatic, human hepatocellular-carcinoma, hbv-dna, liver-disease, human genome, sequences, serum, carcinogenesis, replication, mutations, children, Virology
Subject categories Infectious Medicine


Hepatitis B virus (HBV) infection is the main risk factor for hepatocellular carcinoma (HCC) worldwide. Integration of HBV DNA into the human genome has been found in >80% of HBV-related HCC cases. Some studies have, however, found similar integration patterns in tumorous and nontumorous tissues. Thus, the role of integrations for the development of HCC as well as the rate of integration in different stages of infection remain unclear. The aim of this study was to investigate integrations in patients without HCC, representing different stages of chronic HBV (CHB) infection. Extracted DNA in liver biopsies from 74 patients (one with 2 available biopsies) with CHB infection was analyzed by Alu-PCR. Amplicons were further analyzed by Sanger sequencing. Integration was detected in 39 biopsies (52%) as an amplicon containing both human and HBV sequences by Alu-PCR with one primer targeting a region in the HBV genome. Integrations were found in patients representing the different stages of CHB infection. A majority of the HBV sequences were located upstream or downstream of nucleotide position 1820, which previously has been identified as a common breakpoint in the HBV genome in integrated sequences. Approximately 60% of the HBV integrations were found in noncoding regions of the human genome. Integrations of HBV DNA into the human genome is an event frequently found in mild phases of chronic hepatitis.

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