The core promoter and proximal precore regions are the most complex portions of the hepatitis B virus(HBV) genome. These regions cooperatively regulate viral replication and differentially regulate the synthesis of th...The core promoter and proximal precore regions are the most complex portions of the hepatitis B virus(HBV) genome. These regions cooperatively regulate viral replication and differentially regulate the synthesis of the viral proteins E,core,and X. Multiple mutations in these regions are associated with the persistency of viral infection and the development of cirrhosis and hepatocellular carcinoma(HCC). In South Korea,nearlyall HBVs are classified as HBV genotype C2; the majority of these viruses have the basal core promoter double mutation,a precore stop mutation,or both. These mutations may play a role in the alteration of viral and clinical features,and abundant and complex mutations are particularly prevalent in the core promoter and proximal precore regions. We previously demonstrated that the accumulation of ≥ 6 mutations at eight key nucleotides located in these regions(G1613A,C1653 T,T1753 V,A1762 T,G1764 A,A1846 T,G1896 A,and G1899A) is a useful marker to predict the development of HCC regardless of advanced liver disease. In addition,certain mutation combinations were predominant in cases with ≥ 4 mutations. In cases with ≤ 5 mutations,a low Hepatitis B e antigen titer(< 35 signal to noise ratio) was indicative of HCC risk. Viral mutation data of the single HBV genotype C2 suggest that the combined effect of the number and pattern of mutations in the core promoter and proximal precore regions is helpful in predicting HCC risk.展开更多
AIM： To investigate if the nucleoside analogue lamivudine （LAM）, a potent inhibitor of HBV replication, could restore the function of dendritic cells derived from patients with chronic hepatitis B （CHB） in an Asi...AIM： To investigate if the nucleoside analogue lamivudine （LAM）, a potent inhibitor of HBV replication, could restore the function of dendritic cells derived from patients with chronic hepatitis B （CHB） in an Asian population.METHODS： Dendritic cells （DCs） derived from mononuclearcytes of patients with chronic HBV infection were cultured in the presence of IL-4, granulocytemacrophage colony-stimulating factors （GM-CSF） and gradient concentrations of LAM （0-2 mmol/L）. Cell morphology was observed under light microscopy. Cell surface molecules, including HI_A-DR, CD80, CD83, and CDla, were analyzed with flow cytometry. The concentrations of IL-6 and IL-12 in the supernatant were assayed by ELISA. T cell proliferation was assayed by methyl thiazoM tetrazolium （MTT）.RESULTS： The expression of CDlα on DC treated with 0.5 mmol/L LAM （LAM-DC 0.5 mmol/L） was significantly higher than that of DC untreated with LAM （54.1 ± 4.21 vs 33.57 ± 3.14, P 〈 0.05）, and so was the expression of CD83 （20.24 ± 2.51 vs 12.83 ± 2.12, P 〈 0.05） as well as the expression of HLA-DR （74.5 ± 5.16 vs 52.8 ± 2.51, P 〈 0.05）. Compared with control group, LAM-DC group （0.5 mmol/L） secreted significantly more IL-12 （910 ± 91.5 vs 268 ± 34.3 pg/mL, P 〈 0.05）, had lower levels of IL-6 in the culture supernatant （28 ± 2.6 vs 55 ± 7.36 pg/mL, P 〈 0.05）, markedly enhanced the stimulatory capacity in the allogeneic mixed leukocyte reaction （MLR） （1.87 ± 0.6 vs 1.24 ± 0.51, P 〈 0.05）.CONCLUSION： The lower expression of phenotypic molecules and impaired allogeneic mixed lymphocyte reaction function of dendritic cells derived from patients with HBV infection could be restored in vitro by incubation with LAM.展开更多
Hepatitis B virus(HBV) is the most common cause of hepatitis worldwide, with nearly 350 million people chronically infected and 600000 deaths per year due to acute liver failure occurring during acute hepatitis or, mo...Hepatitis B virus(HBV) is the most common cause of hepatitis worldwide, with nearly 350 million people chronically infected and 600000 deaths per year due to acute liver failure occurring during acute hepatitis or, more frequently, in HBV-related liver cirrhosis or hepatocellular carcinoma. Ongoing immigration from countries with a high HBV endemicity to those with a low HBV endemicity warrants particular attention to prevent the spread of HBV infection to the native population. This review article analyzes the epidemiology and virological and clinical characteristics of HBV infection in immigrant populations and in their host countries, and suggests prophylactic measures to prevent the spread of this infection. Among the immigrants from different geographical areas, those from South East Asia and sub-Saharan Africa show the highest prevalences of hepatitis B surface antigen(HBs Ag) carriers, in accordance with the high endemicity of the countries of origin. The molecular characteristics of HBV infection in immigrants reflect those of the geographical areas of origin: HBV genotype A and D predominate in immigrants from Eastern Europe, B and C in those from Asia and genotype E in those from Africa. The literature data on the clinical course and treatment of HBs Agpositive immigrants are scanty. The management of HBV infection in immigrant populations is difficult and requires expert personnel and dedicated structures for their assistance. The social services, voluntary operators and cultural mediators are essential to achieve optimized psychological and clinical intervention.展开更多
文摘The core promoter and proximal precore regions are the most complex portions of the hepatitis B virus(HBV) genome. These regions cooperatively regulate viral replication and differentially regulate the synthesis of the viral proteins E,core,and X. Multiple mutations in these regions are associated with the persistency of viral infection and the development of cirrhosis and hepatocellular carcinoma(HCC). In South Korea,nearlyall HBVs are classified as HBV genotype C2; the majority of these viruses have the basal core promoter double mutation,a precore stop mutation,or both. These mutations may play a role in the alteration of viral and clinical features,and abundant and complex mutations are particularly prevalent in the core promoter and proximal precore regions. We previously demonstrated that the accumulation of ≥ 6 mutations at eight key nucleotides located in these regions(G1613A,C1653 T,T1753 V,A1762 T,G1764 A,A1846 T,G1896 A,and G1899A) is a useful marker to predict the development of HCC regardless of advanced liver disease. In addition,certain mutation combinations were predominant in cases with ≥ 4 mutations. In cases with ≤ 5 mutations,a low Hepatitis B e antigen titer(< 35 signal to noise ratio) was indicative of HCC risk. Viral mutation data of the single HBV genotype C2 suggest that the combined effect of the number and pattern of mutations in the core promoter and proximal precore regions is helpful in predicting HCC risk.
文摘AIM： To investigate if the nucleoside analogue lamivudine （LAM）, a potent inhibitor of HBV replication, could restore the function of dendritic cells derived from patients with chronic hepatitis B （CHB） in an Asian population.METHODS： Dendritic cells （DCs） derived from mononuclearcytes of patients with chronic HBV infection were cultured in the presence of IL-4, granulocytemacrophage colony-stimulating factors （GM-CSF） and gradient concentrations of LAM （0-2 mmol/L）. Cell morphology was observed under light microscopy. Cell surface molecules, including HI_A-DR, CD80, CD83, and CDla, were analyzed with flow cytometry. The concentrations of IL-6 and IL-12 in the supernatant were assayed by ELISA. T cell proliferation was assayed by methyl thiazoM tetrazolium （MTT）.RESULTS： The expression of CDlα on DC treated with 0.5 mmol/L LAM （LAM-DC 0.5 mmol/L） was significantly higher than that of DC untreated with LAM （54.1 ± 4.21 vs 33.57 ± 3.14, P 〈 0.05）, and so was the expression of CD83 （20.24 ± 2.51 vs 12.83 ± 2.12, P 〈 0.05） as well as the expression of HLA-DR （74.5 ± 5.16 vs 52.8 ± 2.51, P 〈 0.05）. Compared with control group, LAM-DC group （0.5 mmol/L） secreted significantly more IL-12 （910 ± 91.5 vs 268 ± 34.3 pg/mL, P 〈 0.05）, had lower levels of IL-6 in the culture supernatant （28 ± 2.6 vs 55 ± 7.36 pg/mL, P 〈 0.05）, markedly enhanced the stimulatory capacity in the allogeneic mixed leukocyte reaction （MLR） （1.87 ± 0.6 vs 1.24 ± 0.51, P 〈 0.05）.CONCLUSION： The lower expression of phenotypic molecules and impaired allogeneic mixed lymphocyte reaction function of dendritic cells derived from patients with HBV infection could be restored in vitro by incubation with LAM.
文摘Hepatitis B virus(HBV) is the most common cause of hepatitis worldwide, with nearly 350 million people chronically infected and 600000 deaths per year due to acute liver failure occurring during acute hepatitis or, more frequently, in HBV-related liver cirrhosis or hepatocellular carcinoma. Ongoing immigration from countries with a high HBV endemicity to those with a low HBV endemicity warrants particular attention to prevent the spread of HBV infection to the native population. This review article analyzes the epidemiology and virological and clinical characteristics of HBV infection in immigrant populations and in their host countries, and suggests prophylactic measures to prevent the spread of this infection. Among the immigrants from different geographical areas, those from South East Asia and sub-Saharan Africa show the highest prevalences of hepatitis B surface antigen(HBs Ag) carriers, in accordance with the high endemicity of the countries of origin. The molecular characteristics of HBV infection in immigrants reflect those of the geographical areas of origin: HBV genotype A and D predominate in immigrants from Eastern Europe, B and C in those from Asia and genotype E in those from Africa. The literature data on the clinical course and treatment of HBs Agpositive immigrants are scanty. The management of HBV infection in immigrant populations is difficult and requires expert personnel and dedicated structures for their assistance. The social services, voluntary operators and cultural mediators are essential to achieve optimized psychological and clinical intervention.
