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Open Access Research

A pre-S gene chip to detect pre-S deletions in hepatitis B virus large surface antigen as a predictive marker for hepatoma risk in chronic hepatitis B virus carriers

Fan-Ching Shen1, Ih-Jen Su4, Han-Chieh Wu4, Yi-Hsuan Hsieh2, Wei-Jen Yao6, Kung-Chia Young1, Tsung-Chuan Chang1, Hui-Chuan Hsieh2, Han-Ni Tsai2 and Wenya Huang1235*

Author Affiliations

1 Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, Taiwan, Republic of China

2 Institute of Basic Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China

3 Center for Signal Transduction and Gene Regulation, National Cheng Kung University, Tainan, Taiwan, Republic of China

4 Division of Infectious Diseases, National Health Research Institutes, Tainan, Taiwan, Republic of China

5 Laboratory of Molecular Diagnostics, Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan, Republic of China

6 Department of Radiology, National Cheng Kung University Hospital, Tainan, Taiwan, Republic of China

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Journal of Biomedical Science 2009, 16:84  doi:10.1186/1423-0127-16-84

Published: 15 September 2009

Abstract

Background

Chronic hepatitis B virus (HBV) infection is an important cause of hepatocellular carcinoma (HCC) worldwide. The pre-S1 and -S2 mutant large HBV surface antigen (LHBS), in which the pre-S1 and -S2 regions of the LHBS gene are partially deleted, are highly associated with HBV-related HCC.

Methods

The pre-S region of the LHBS gene in two hundred and one HBV-positive serum samples was PCR-amplified and sequenced. A pre-S oligonucleotide gene chip was developed to efficiently detect pre-S deletions in chronic HBV carriers. Twenty serum samples from chronic HBV carriers were analyzed using the chip.

Results

The pre-S deletion rates were relatively low (7%) in the sera of patients with acute HBV infection. They gradually increased in periods of persistent HBV infection: pre-S mutation rates were 37% in chronic HBV carriers, and as high as 60% in HCC patients. The Pre-S Gene Chip offers a highly sensitive and specific method for pre-S deletion detection and is less expensive and more efficient (turnaround time 3 days) than DNA sequencing analysis.

Conclusion

The pre-S1/2 mutants may emerge during the long-term persistence of the HBV genome in carriers and facilitate HCC development. Combined detection of pre-S mutations, other markers of HBV replication, and viral titers, offers a reliable predictive method for HCC risks in chronic HBV carriers.