Significant association of different preS mutations with hepatitis B-related cirrhosis or hepatocellular carcinoma
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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.
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.
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.
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.
KeywordsHepatitis B virus Mutation PreS Hepatocellular carcinoma Liver cirrhosis
Adjusted odds ratio
Asymptomatic hepatitis B surface antigen carrier
Chronic hepatitis B
Hepatitis B virus
Hepatitis B e antigen
Hepatitis B surface antigen
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.