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Integration of hepatitis B virus DNA in chronically infected patients assessed by Alu‐PCR
Author(s) -
Larsson Simon B.,
Tripodi Gianluca,
Raimondo Giovanni,
Saitta Carlo,
Norkrans Gunnar,
Pollicino Teresa,
Lindh Magnus
Publication year - 2018
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.25227
Subject(s) - hepatitis b virus , virology , amplicon , biology , hepatocellular carcinoma , genome , polymerase chain reaction , sanger sequencing , hepatitis b , virus , dna sequencing , dna , gene , genetics
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.