Association of Hepatitis B Virus Pre-S Deletions with the Development of Hepatocellular Carcinoma in Chronic Hepatitis B

• Published in: The Journal of infectious diseases 2011-03, Vol.203 (5), p.646-654
• Main Authors: Yeung, Pok, Wong, Danny Ka-Ho, Lai, Ching-Lung, Fung, James, Seto, Wai-Kay, Yuen, Man-Fung
• Format: Article
• Language: English
• Subjects: Adult; Aged; Amino Acid Sequence; Biological and medical sciences; Carcinoma, Hepatocellular - epidemiology; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - virology; Case-Control Studies; Chronic hepatitis; Databases, Nucleic Acid; Developmental biology; DNA Primers; Female; Fundamental and applied biological sciences. Psychology; Gene Deletion; Genetic mutation; Genotype; Genotypes; Hepatitis antigens; Hepatitis B Surface Antigens - chemistry; Hepatitis B Surface Antigens - genetics; Hepatitis B virus; Hepatitis B virus - chemistry; Hepatitis B virus - classification; Hepatitis B virus - genetics; Hepatitis B, Chronic - complications; Hepatitis B, Chronic - genetics; Hepatitis B, Chronic - virology; Hepatocellular carcinoma; Hong Kong - epidemiology; Human viral diseases; Humans; Infections; Infectious diseases; Liver Neoplasms - epidemiology; Liver Neoplasms - genetics; Liver Neoplasms - virology; Major and Brief Reports; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Mutation; Polymerase Chain Reaction; Protein Precursors - chemistry; Protein Precursors - genetics; Risk Factors; Sequence Alignment; Start codon; Tumors; Viral diseases; Viral hepatitis; Virology; VIRUSES
• ISSN: 0022-1899; 1537-6613; 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiq096

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.