AIM: To investigate the frequency of mutations in pre-core (pre-C) and basic core promoter (BCP) regions of hepatitis B virus (HBV) from Shanxi Province, and the association between mutations and disease related index...AIM: To investigate the frequency of mutations in pre-core (pre-C) and basic core promoter (BCP) regions of hepatitis B virus (HBV) from Shanxi Province, and the association between mutations and disease related indexes.METHODS: One hundred chronic hepatitis B patients treated at Shanxi Province Hospital of Traditional Chinese Medicine were included in this study. PCR-reverse dot blot hybridization and mismatch amplification mutation assay (MAMA)-PCR were used to detect the mutations in the HBV pre-C and BCP regions. HBV DNA content and liver function were compared between patients with mutant HBV pre-C and BCP loci and those with wild-type loci. The consistency between PCR-reverse dot blot hybridization and MAMA-PCR for detecting mutations in the HBV pre-C and BCP regions was assessed.RESULTS: Of the 100 serum samples detected, 9.38% had single mutations in the pre-C region, 29.17% had single mutations in the BCP region, 41.67% had mutations in both BCP and pre-C regions, and 19.79% had wild-type loci. The rates of BCP and pre-C mutations were 65.7% and 34.3%, respectively, in hepatitis B e antigen (HBeAg) positive patients, and 84.6% and 96.2%, respectively, in HBeAg negative patients. The rate of pre-C mutations was significantly higher in HBeAg negative patients than in HBeAg positive patients (χ<sup>2</sup> = 26.62, P = 0.00), but there was no significant difference in the distribution of mutations in the BCP region between HBeAg positive and negative patients (χ<sup>2</sup> = 2.43, P = 0.12). The presence of mutations in the pre-C (Wilcoxon W = 1802.5, P = 0.00) and BCP regions (Wilcoxon W = 2906.5, P = 0.00) was more common in patients with low HBV DNA content. Both AST and GGT were significantly higher in patients with mutant pre-C and BCP loci than in those with wild-type loci (P < 0.05). PCR-reverse dot blot hybridization and MAMA-PCR for detection of mutations in the BCP and pre-C regions had good consistency, and the Kappa values obtained were 0.91 and 0.58, respectively.CONCLUSION: HBeAg negative patients tend to have HBV pre-C mutations. However, these mutations do not cause increased DNA copies, but associate with damage of liver function.展开更多
The Hepatitis B Virus(HBV) has a worldwide distribu-tion and is endemic in many populations. It is constantly evolving and 10 genotypic strains have been identified with varying prevalences in different geographic reg...The Hepatitis B Virus(HBV) has a worldwide distribu-tion and is endemic in many populations. It is constantly evolving and 10 genotypic strains have been identified with varying prevalences in different geographic regions. Numerous stable mutations in the core gene and in the su-rface gene of the HBV have also been identified in untreated HBV populations. The genotypes and viral variants have been associated with certain clinical featu-res of HBV related liver disease and Hepatocellu-lar carcinoma. For example Genotype C is associated withlater hepatitis B e antigen(HBe Ag) seroconversion, and more advanced liver disease. Genotype A is associated with a greater risk of progression to chronicity in adu-lt acqu-ired HBV infections. Genotype D is particu-larly associated with the precore mu-tation and HBe Ag negative chronic hepatitis B(CHB). The genotypes prevalent in parts of West Africa, Central and Sou-th America, E, F and H respectively, are less well stu-died. Viral variants especially the Basal Core Promotor mutation is associated with increased risk of fibrosis and cancer of the liver. Althou-gh not cu-rrently part of rou-tine clinical care, evalu-ation of genotype and viral variants may provide u-sefu-l adju-nctive information in predicting risk abou-t liver related morbidity in patients with CHB.展开更多
基金Supported by Youth Foundation of Health and Family Planning Commission of Shanxi ProvinceNo.201301024
文摘AIM: To investigate the frequency of mutations in pre-core (pre-C) and basic core promoter (BCP) regions of hepatitis B virus (HBV) from Shanxi Province, and the association between mutations and disease related indexes.METHODS: One hundred chronic hepatitis B patients treated at Shanxi Province Hospital of Traditional Chinese Medicine were included in this study. PCR-reverse dot blot hybridization and mismatch amplification mutation assay (MAMA)-PCR were used to detect the mutations in the HBV pre-C and BCP regions. HBV DNA content and liver function were compared between patients with mutant HBV pre-C and BCP loci and those with wild-type loci. The consistency between PCR-reverse dot blot hybridization and MAMA-PCR for detecting mutations in the HBV pre-C and BCP regions was assessed.RESULTS: Of the 100 serum samples detected, 9.38% had single mutations in the pre-C region, 29.17% had single mutations in the BCP region, 41.67% had mutations in both BCP and pre-C regions, and 19.79% had wild-type loci. The rates of BCP and pre-C mutations were 65.7% and 34.3%, respectively, in hepatitis B e antigen (HBeAg) positive patients, and 84.6% and 96.2%, respectively, in HBeAg negative patients. The rate of pre-C mutations was significantly higher in HBeAg negative patients than in HBeAg positive patients (χ<sup>2</sup> = 26.62, P = 0.00), but there was no significant difference in the distribution of mutations in the BCP region between HBeAg positive and negative patients (χ<sup>2</sup> = 2.43, P = 0.12). The presence of mutations in the pre-C (Wilcoxon W = 1802.5, P = 0.00) and BCP regions (Wilcoxon W = 2906.5, P = 0.00) was more common in patients with low HBV DNA content. Both AST and GGT were significantly higher in patients with mutant pre-C and BCP loci than in those with wild-type loci (P < 0.05). PCR-reverse dot blot hybridization and MAMA-PCR for detection of mutations in the BCP and pre-C regions had good consistency, and the Kappa values obtained were 0.91 and 0.58, respectively.CONCLUSION: HBeAg negative patients tend to have HBV pre-C mutations. However, these mutations do not cause increased DNA copies, but associate with damage of liver function.
文摘The Hepatitis B Virus(HBV) has a worldwide distribu-tion and is endemic in many populations. It is constantly evolving and 10 genotypic strains have been identified with varying prevalences in different geographic regions. Numerous stable mutations in the core gene and in the su-rface gene of the HBV have also been identified in untreated HBV populations. The genotypes and viral variants have been associated with certain clinical featu-res of HBV related liver disease and Hepatocellu-lar carcinoma. For example Genotype C is associated withlater hepatitis B e antigen(HBe Ag) seroconversion, and more advanced liver disease. Genotype A is associated with a greater risk of progression to chronicity in adu-lt acqu-ired HBV infections. Genotype D is particu-larly associated with the precore mu-tation and HBe Ag negative chronic hepatitis B(CHB). The genotypes prevalent in parts of West Africa, Central and Sou-th America, E, F and H respectively, are less well stu-died. Viral variants especially the Basal Core Promotor mutation is associated with increased risk of fibrosis and cancer of the liver. Althou-gh not cu-rrently part of rou-tine clinical care, evalu-ation of genotype and viral variants may provide u-sefu-l adju-nctive information in predicting risk abou-t liver related morbidity in patients with CHB.