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Significant association of different preS mutations with hepatitis B-related cirrhosis or hepatocellular carcinoma

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

The associations of nucleotide substitution mutations in the preS region of hepatitis B virus (HBV) with hepatocellular carcinoma (HCC) and cirrhosis remain unknown. We aimed to determine the associations of preS mutations with HCC or cirrhosis.

Methods

HBV from 603 asymptomatic hepatitis B surface antigen carriers (ASCs), 219 chronic hepatitis B (CHB) patients, 119 cirrhosis patients, and 231 HCC patients were genotyped and sequenced in the preS region. Nucleotides with the highest frequencies in HBV from the hepatitis B e antigen (HBeAg)-positive ASCs were treated as “wild-type” nucleotides. Twenty-one preS1 mutations and 14 preS2 mutations were evaluated. Multivariate regression analyses were applied to determine factors independently associated with cirrhosis or HCC.

Results

Most (85.7%) preS2 mutations were associated with CHB compared with ASCs, whereas most preS1 mutations were associated with HCC compared with the cirrhosis patients or CHB patients. Compared with the CHB patients, 81.0% preS1 mutations in genotype C were inversely associated with cirrhosis. Multivariate regression analyses showed that C2964A, C3116T, and C7A were novel factors associated with HCC compared with those without HCC, whereas A2964C and T3116C were independently associated with cirrhosis compared with ASCs and the CHB patients. Combined preS1 mutations had specificities greater than 95%, while C3116T and C7A had moderate sensitivities and specificities, for HCC.

Conclusions

C2964A, C3116T, and C7A are novel markers independently associated with an increased risk of HCC, while A2964C and T3116C are novel markers independently associated with an increased risk of cirrhosis. Combined preS1 mutations are specific for HCC.

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Abbreviations

ALT:

Alanine aminotransferase

AOR:

Adjusted odds ratio

ASC:

Asymptomatic hepatitis B surface antigen carrier

CHB:

Chronic hepatitis B

HBV:

Hepatitis B virus

HBeAg:

Hepatitis B e antigen

HBsAg:

Hepatitis B surface antigen

HCC:

Hepatocellular carcinoma

LC:

Liver cirrhosis

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Acknowledgments

We thank the members of our epidemiological teams for their help in field epidemiological study. This work was supported by grants from Ministry of Health of China (2008ZX10002-15), National Natural Science Foundation of China (30921006, 30901272), and Shanghai Science & Technology Committee (08XD14001).

Conflict of interest statement

No conflicts of interest exist.

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Authors and Affiliations

  1. Department of Epidemiology, Second Military Medical University, 800 Xiang-yin Rd., Shanghai, 200433, China

    Jianhua Yin, Jiaxin Xie, Hongwei Zhang, Qiuxia Shen, Lei Han, Wenying Lu, Yifang Han & Guangwen Cao

  2. Department of Infectious Disease, The 1st Affiliated Hospital, Second Military Medical University, Shanghai, China

    Chengzhong Li

  3. Department of Infectious Disease, The 2nd Affiliated Hospital, Second Military Medical University, Shanghai, China

    Wu Ni

  4. Laboratory for Signal Transduction, The 3rd Affiliated Hospital, Second Military Medical University, Shanghai, China

    Hongyang Wang

Authors
  1. Jianhua Yin
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  9. Wu Ni
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Corresponding author

Correspondence to Guangwen Cao.

Additional information

J. Yin and J. Xie contributed equally to this work.

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Yin, J., Xie, J., Zhang, H. et al. Significant association of different preS mutations with hepatitis B-related cirrhosis or hepatocellular carcinoma. J Gastroenterol 45, 1063–1071 (2010). https://doi.org/10.1007/s00535-010-0253-1

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  • DOI: https://doi.org/10.1007/s00535-010-0253-1

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