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Association of hepatitis B virus pre-S deletions with the development of hepatocellular carcinoma in chronic hepatitis B.

ABSTRACT: BACKGROUND: We aimed to determine whether hepatitis B virus (HBV) pre-S deletion was an independent factor for the development of hepatocellular carcinoma (HCC). METHODS: Pre-S deletions were determined in HBV isolates from 115 chronic hepatitis B (CHB) patients with HCC. Sixty-nine patients were further matched with 69 CHB patients without HCC for age, sex, hepatitis B e antigen (HBeAg) status, and HBV genotype. RESULTS: HBV pre-S deletions were clustered mainly in the 3' end of pre-S1 and 5' end of pre-S2 regions. Adjusted for confounding risk factors, patients with HCC had a higher prevalence of HBV with pre-S deletions than did patients without HCC (23 [33.3%] of 69 vs 11 [15.9%] of 69; P = .018; odds ratio [OR], 2.64). In particular, only pre-S2 deletions but not pre-S1 deletions were significantly associated with the development of HCC (P = .020). A higher prevalence of pre-S deletions was observed in HBV isolates from HCC patients under the age of 50 years than from those older than 50 years (10 [62.5%] of 16 vs 13 [24.5%] of 53; P = .012; OR, 5.13). Emergence of de novo pre-S deletions was documented before the development of HCC. CONCLUSIONS: HBV pre-S2 deletions were an independent factor associated with the development of HCC. Its oncogenic role may be more important in young patients with HCC.

SUBMITTER: Yeung P

PROVIDER: S-EPMC3072715 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Association of hepatitis B virus pre-S deletions with the development of hepatocellular carcinoma in chronic hepatitis B.

Yeung Pok P Wong Danny Ka-Ho DK Lai Ching-Lung CL Fung James J Seto Wai-Kay WK Yuen Man-Fung MF

The Journal of infectious diseases 20110112 5

<h4>Background</h4>We aimed to determine whether hepatitis B virus (HBV) pre-S deletion was an independent factor for the development of hepatocellular carcinoma (HCC).<h4>Methods</h4>Pre-S deletions were determined in HBV isolates from 115 chronic hepatitis B (CHB) patients with HCC. Sixty-nine patients were further matched with 69 CHB patients without HCC for age, sex, hepatitis B e antigen (HBeAg) status, and HBV genotype.<h4>Results</h4>HBV pre-S deletions were clustered mainly in the 3' end ...[more]

PMID: 21227916

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Project description:To develop a novel non-sequencing method for the detection of hepatitis B virus (HBV) pre-S deletion mutants in HBV carriers.The entire region of HBV pre-S1 and pre-S2 was amplified by polymerase chain reaction (PCR). The size of PCR products was subsequently determined by capillary gel electrophoresis (CGE). CGE were carried out in a PACE-MDQ instrument equipped with a UV detector set at 254 nm. The samples were separated in 50 ?m ID eCAP Neutral Coated Capillaries using a voltage of 6 kV for 30 min. Data acquisition and analysis were performed using the 32 Karat Software. A total of 114 DNA clones containing different sizes of the HBV pre-S gene were used to determine the accuracy of the CGE method. One hundred and fifty seven hepatocellular carcinoma (HCC) and 160 non-HCC patients were recruited into the study to assess the association between HBV pre-S deletion and HCC by using the newly-established CGE method. Nine HCC cases with HBV pre-S deletion at the diagnosis year were selected to conduct a longitudinal observation using serial serum samples collected 2-9 years prior to HCC diagnosis.CGE allowed the separation of PCR products differing in size > 3 bp and was able to identify 10% of the deleted DNA in a background of wild-type DNA. The accuracy rate of CGE-based analysis was 99.1% compared with the clone sequencing results. Using this assay, pre-S deletion was more frequently found in HCC patients than in non-HCC controls (47.1% vs 28.1%, P < 0.001). Interestingly, the increased risk of HCC was mainly contributed by the short deletion of pre-S. While the deletion ? 99 bp was associated with a 2.971-fold increased risk of HCC (95%CI: 1.723-5.122, P < 0.001), large deletion (> 99 bp) did not show any association with HCC (P = 0.918, OR = 0.966, 95%CI: 0.501-1.863). Of the 9 patients who carried pre-S deletions at the stage of HCC, 88.9% (8/9) had deletions 2-5 years prior to HCC, while only 44.4%4 (4/9) contained such deletions 6-9 years prior to HCC.CGE is a sensitive approach for HBV pre-S deletion analysis. Pre-S deletion, especially for short DNA fragment deletion, is a useful predictive marker for HCC.

Dataset Information

Association of hepatitis B virus pre-S deletions with the development of hepatocellular carcinoma in chronic hepatitis B.

Publications

Association of hepatitis B virus pre-S deletions with the development of hepatocellular carcinoma in chronic hepatitis B.

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