0% to 4.2% in genotype C) in ASCs but equally high in the CHB patients, HC patients, and HCC patients (92.3% Trichostatin A to 100.0% in genotype B and 89.7% to 100.0% in genotype C). Table 3 Associations of nucleotide substitutions in the EnhII/BCP/PC region of HBV genotypes B and C with cirrhosis and HCC Table 4 Associations of nucleotide substitutions in the pre-S region of HBV genotypes B and C with cirrhosis and HCC Association of HLA-DP polymorphisms with HBV mutations. We then assessed the associations of the HLA SNPs with all the significant HC- or HCC-related HBV mutations (Tables 3 and and4)4) in the subjects with genotype B and those with genotype C infections, respectively.

Generally, the HLA-DP polymorphisms promoting HBV clearance were significantly associated with a lower prevalence of HBV mutations increasing HCC risk and a higher prevalence of the mutations decreasing HCC risk in both HBV genotypes, in spite of several exceptions (Table 5). Table 5 Significant associations of HLA-DP polymorphisms with frequencies of HBV mutations associates with liver disease riskd We then investigated the distribution of the HLA-DP SNP-affected HBV mutations in the 4 clinical stages of HBV evolution. In the genotype C group, T1674C/G, A1846T, and G1896A mutations were more frequent in the patients with HBV-related liver diseases (CHB, HC, and HCC) than in ASCs (P < 0.001 for each comparison). The 3 mutations were more frequent in the CHB patients than in the HC patients, while T1674C/G and A1846T mutations were more frequent in the HCC patients than in the HC patients.

However, the C1673T, A1727T, C1730G, and C1799G mutations were more frequent in ASCs and the HC patients than in the CHB patients and the HCC patients, respectively. In the genotype B group, the pattern of the HBV mutations in the EnhII/BCP/PC region in the 4 stages was different from that of the genotype C group. The frequencies of HBV mutations in the pre-S2 region were very low in ASCs but equally high in the CHB, HC, and HCC patients infected with either genotype B or genotype C. The frequencies of C1653T, pre-S deletion, and pre-S2 start codon mutations in genotype C increased successively from the ASC state to HCC (Ptrend < 0.001 for each). These data are presented in Fig 1.

Fig 1 Frequencies of HLA-DP GSK-3 genetic polymorphism-affected HBV mutations in asymptomatic hepatitis B surface antigen carriers (ASCs), chronic hepatitis B (CHB) patients, hepatic cirrhosis (HC) patients, and hepatocellular carcinoma (HCC) patients. (A) Mutations … Effects of interactions of the HLA-DP polymorphisms with the HBV mutations on the risks of HC and HCC. Multiplicative interactions of the HLA SNPs with all the significant HC- or HCC-related HBV mutations in the subjects with genotype B and those with genotype C infections were evaluated, respectively.