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. 2011 Mar 1;203(5):646-54.
doi: 10.1093/infdis/jiq096. Epub 2011 Jan 12.

Association of Hepatitis B Virus pre-S Deletions With the Development of Hepatocellular Carcinoma in Chronic Hepatitis B

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Free PMC article

Association of Hepatitis B Virus pre-S Deletions With the Development of Hepatocellular Carcinoma in Chronic Hepatitis B

Pok Yeung et al. J Infect Dis. .
Free PMC article

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.

Figures

Figure 1.
Figure 1.
Alignment of amino acid sequences with pre-S deletion from 14 non-HCC and 28 HCC patients. The wild type consensus sequences are represented by AB073847 (genotype B) and AF068756 (genotype C). Dots represent amino acids that may or may not be identical to the consensus sequences. Slashes represent deletion of amino acids. The names of the isolates correspond to those in Table 2. The start sites of preS1 (aa 1) and preS2 (aa 120), hepatocyte binding site (aa 21 − 47), S promoter (nt 3045 − 3180), CCAAT box (nt 3137 − 3141), and human serum albumin receptor (aa 17 − 28) are marked correspondingly at the top of the alignment. aa, amino acid; HCC, hepatocellular carcinoma; nt, nucleotide.
Figure 2.
Figure 2.
Prevalence of different types of pre-S deletions in 2 clinical groups according to (a) hepatitis B virus (HBV) genotype, (b) gender, (c) age group, and (d) hepatitis B e antigen (HBeAg) status. The number in parentheses on each column represents the overall prevalence of pre-S deletion in that category.
Figure 3.
Figure 3.
Schematic representation showing the status of pre-S deletion in serial samples from 15 hepatocellular carcinoma (HCC) patients with chronic hepatitis B virus (HBV) infection. Each sample is depicted as a block and its location relative to the timeline indicates the time before diagnosis of HCC. Empty blocks represent samples with no pre-S deletion, whereas shaded blocks represent samples with pre-S deletion. Demographic details of the HBV isolates at the time of diagnosis of HCC are listed at the right panel. There is no change in the pre-S deletions in all serial samples except the one labeled with an asterisk (*) where the pre-S1 deletion identified in the later samples is not found.

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