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Relationship between hepatocellular carcinoma and hepatitis B virus genotype with spontaneous YMDD mutations.

ABSTRACT: To investigate the relationship between hepatitis B virus (HBV) genotype with spontaneous YMDD mutations and hepatocellular carcinoma (HCC) in HBV-related cirrhosis.We investigated 264 liver cirrhosis patients who were not treated with antiviral drugs, including 81 patients with HCC. YMDD mutations were detected by fluorescent hybridization bioprobe polymerase chain reaction (PCR) and melting curve assay using the Diagnosis Kit for HBV YMDD Mutation. Serum HBV genotypes were detected by real-time PCR using genotype-specific TaqMan probes. Statistical analysis was performed according to data type using the t test, ?(2) test and unconditional logistic regression analysis.In the HCC group, genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (40.74%), 13 (16.05%) and 11 (13.58%) patients, respectively. In the liver cirrhosis (LC) group, HBV genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (18.03%), 7 (3.83%) and 2 (1.09%) patients, respectively. The differences in genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations between the two groups were statistically significant (?(2) = 15.441, P = 0.000; ?(2) = 11.983, P = 0.001; P = 0.000). In the HCC and LC groups, there were seven patients infected by genotype B strains with YMDD mutations and 13 by genotype C strains with YMDD mutations. Further research revealed that HCC occurred in 2 patients infected by genotype B strains with YMDD mutations and 11 infected by genotype C strains with YMDD mutations. The difference was statistically significant (P = 0.000). Unconditional logistic regression analysis revealed that patients infected by genotype C strains with spontaneous YMDD mutations had a 7.775-fold higher risk for the development of HBV-related HCC than patients infected by other type HBV strains (P = 0.013, 95%CI: 1.540-39.264).Genotype C strains with spontaneous YMDD mutations are an independent risk factor for HCC in LC patients and are important for early warning of HCC.

SUBMITTER: Yang JH

PROVIDER: S-EPMC3699046 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Relationship between hepatocellular carcinoma and hepatitis B virus genotype with spontaneous YMDD mutations.

Yang Jia-Hong JH Zhang Hao H Chen Xue-Bing XB Chen Gao G Wang Xiu X

World journal of gastroenterology 20130601 24

<h4>Aim</h4>To investigate the relationship between hepatitis B virus (HBV) genotype with spontaneous YMDD mutations and hepatocellular carcinoma (HCC) in HBV-related cirrhosis.<h4>Methods</h4>We investigated 264 liver cirrhosis patients who were not treated with antiviral drugs, including 81 patients with HCC. YMDD mutations were detected by fluorescent hybridization bioprobe polymerase chain reaction (PCR) and melting curve assay using the Diagnosis Kit for HBV YMDD Mutation. Serum HBV genotyp ...[more]

PMID: 23840126

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Project description:BackgroundThe association between hepatitis B virus (HBV) mutations and hepatocarcinogenesis remains controversial because of conflicting data in the literature. We conducted a meta-analysis of case-control and cohort studies to examine HBV PreS, enhancer II (EnhII), basal core promoter (BCP), and precore mutations in relation to the risk of hepatocellular carcinoma (HCC).MethodsWe searched databases for studies of these associations that were published in English or Chinese up to August 31, 2008. HBV mutation-specific odds ratios and relative risks were pooled by use of a random-effects model and stratified by potential confounders. All statistical tests were two-sided.ResultsOf the 43 studies included in this meta-analysis, 40 used a case-control design. The 43 studies evaluated a total of 11 582 HBV-infected participants, of whom 2801 had HCC. Statistically significant summary odds ratios of HCC were obtained for any PreS mutation (3.77, 95% confidence interval [CI] = 2.57 to 5.52), C1653T in EnhII (2.76, 95% CI = 2.09 to 3.64), T1753V (2.35, 95% CI = 1.63 to 3.40), and A1762T/G1764A in BCP (3.79, 95% CI = 2.71 to 5.29). PreS mutations were more strongly associated with an increased risk of HCC in subjects who were infected with HBV genotype C than in those who were infected with HBV genotype B, whereas the opposite was true for A1762T/G1764A. C1653T, T1753V, and A1762T/G1764A were more strongly associated with an increased risk of HCC in hepatitis B e antigen (HBeAg)-positive subjects than in HBeAg-negative subjects. PreS mutations, C1653T, T1753V, and A1762T/G1764A accumulated during the progression of chronic HBV infection from the asymptomatic carrier state to HCC (P(trend) < .001 for each mutation). PreS mutations, C1653T, C1653T + T1753V, and A1762T/G1764A-based combinations of mutations had specificities greater than 80% for the prediction of HCC. The precore mutations G1896A and C1858T were not associated with the risk of HCC, regardless of HBeAg status and HBV genotype.ConclusionsHBV PreS mutations, C1653T, T1753V, and A1762T/G1764A are associated with an increased risk of HCC. These mutations alone and in combination may be predictive for hepatocarcinogenesis.

Dataset Information

Relationship between hepatocellular carcinoma and hepatitis B virus genotype with spontaneous YMDD mutations.

Publications

Relationship between hepatocellular carcinoma and hepatitis B virus genotype with spontaneous YMDD mutations.

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