乙型肝炎病毒(hepatitis B virus,HBV)感染是一个严重的公共卫生问题。据世界卫生组织(World Health Organization,WHO)报道,全球60亿人口中,约20亿人曾感染过HBV,其中3.5亿人为慢性HBV感染,每年约有1 00万人死于HBV感染所致的肝衰竭、...乙型肝炎病毒(hepatitis B virus,HBV)感染是一个严重的公共卫生问题。据世界卫生组织(World Health Organization,WHO)报道,全球60亿人口中,约20亿人曾感染过HBV,其中3.5亿人为慢性HBV感染,每年约有1 00万人死于HBV感染所致的肝衰竭、肝硬化和原发性肝细胞癌(肝癌)[1]。全球肝癌患者中,75%以上是HBV所致[2]。展开更多
Chronic hepatitis B is one of the most common epidemic diseases in China and has become a majorhealth issue. To help standardize the prevention, diagnosis, and treatment of chronic hepatitis B, the Guideline on preven...Chronic hepatitis B is one of the most common epidemic diseases in China and has become a majorhealth issue. To help standardize the prevention, diagnosis, and treatment of chronic hepatitis B, the Guideline on prevention and treatment of chronic hepatitis B （abbr. Guideline） was created by a group of appropriate experts belonging to the Society of Hepatology and the Society of Infectious Disease, the Chinese Medical Association according to the principles of evidence-based medicine using the latest clinical research data. The evidence used to formulate the recommendation has been classified into 3 classes and 5 grades, which are indicated by Roman numerals in brackets.展开更多
AIM: G1896A mutation in precore or A1762T/G1764Amutations in basal core promoter are suspected to be responsible for patients with detectable level of HBV DNA in serum after seroconversion from HBeAg to anti-Hbe. Howe...AIM: G1896A mutation in precore or A1762T/G1764Amutations in basal core promoter are suspected to be responsible for patients with detectable level of HBV DNA in serum after seroconversion from HBeAg to anti-Hbe. However, G1896A variant has impaired, while A1762T/ G1764A variant may have intact replication ability. They themselves or their coexistence status may play different roles in such meaningless seroconversion. For these reasons, the significances of these two types of mutations were comparatively investigated in this study. METHODS: One hundred and sixty-five sera with positive anti-Hbe and HBV DNA were collected from different patients. Mutations of G1896A and A1762T/G1764A among these serum samples were detected using competitively differentiated PCR. HBV DNA was demonstrated using real-time quantitative PCR. RESULTS: G1896A and/or A1762T/G1764A mutations were detected in 89.1% (147/165) out of patients with detectable HBV DNA in serum after HBeAg-to-anti-Hbe seroconversion. The positive rate of G1896A variants was significantly higher than that of A1762T/G1764A mutations (77.6% vs 50.3%, X2 = 26.61, P＜0.01). The coexistence positive rate of these two types of mutations was 38.8% (64/165). Coexistence mutations were found in 77.1% (64/83) out of sera with A1762T/G1764A mutations, and in 50.0% (64/128) out of sera with G1896A mutation. Compared with variants with G1896A mutation only, the coexistence mutations were predominant in patients with high level of serum HBV DNA, and related to higher total bilirubin, lower serum albumin and progressive liver diseases. CONCLUSION: The coexistence of G1896A mutation and A1762T/G1764A mutations is very common, and responsible for the major cases with high level of HBV DNA in serum and progressive liver diseases after HBeAg-to-anti-Hbe seroconversion. This coexistence mutation variant may have higher pathogenicity and replication ability.展开更多
Hepatitis B virus （HBV） infection occurs primarily in hepatocytes in the liver with release of infectious virions and non-infectious empty surface antigen particles into the bloodstream. HBV replication is non-cytop...Hepatitis B virus （HBV） infection occurs primarily in hepatocytes in the liver with release of infectious virions and non-infectious empty surface antigen particles into the bloodstream. HBV replication is non-cytopathic. Transient infections run a course of several months, and chronic infections are often life-long. Chronic infections can lead to liver failure with cirrhosis and hepatocellniar carcinoma. It is generally accepted that neutralizing anti-HBs antibodies plays a key role in recovery from HBV infection by containing the spread of infection in the infected host and facilitating the removal and destruction of viral particles. However, the immune response initiated by the T-cell response to viral antigens is also important for viral clearance and disease pathogenesis in HBV infection. The three structural forms of the viral proteins, the HBsAg, the particulate HBcAg, and the nonparticulate HBeAg, may preferentially elicit different Th cell subsets. The different IgG subclass profiles of anti-HBs, anti-HBc, and anti-HBe in different HBV infection status were revealed. Moreover, the different IgG subclass profiles in chronic carriers did not change with different ALT and AST levels and may reflect the difference between stimulating antigens, immune response, and the stages of viral disease and provide the basis for the use of vaccines and prophylactic treatments for individuals at high risk of human HBV infection. This review elucidates the detailed understanding of the immune responses induced during transient and persistent infection, and the development of immunotherapy and immunodiagnosis in patients with HBV infection, and possible means of reducing the liver damage.展开更多
AIM: Attaining hepatitis B e antigen (HBeAg) seroconversion during lamivudine treatment is associated with fewer relapses in HBeAg-positive patients. In HBeAg-negative patients,predictors for post-treatment relapse re...AIM: Attaining hepatitis B e antigen (HBeAg) seroconversion during lamivudine treatment is associated with fewer relapses in HBeAg-positive patients. In HBeAg-negative patients,predictors for post-treatment relapse remain largely unknown.We therefore studied whether end-of-treatment virologic response correlated with relapse after lamivudine treatment.METHODS: We prospectively analyzed 12 HBeAg-negative patients and 14 HBeAg-positive patients with chronic hepatitis B, who received at least 9 mo of lamivudine treatment and were followed up for 12 mo post-treatment. Relapse of hepatitis B activity was defined by an elevation of serum ALT level above twice the upper limit of normal as well as reappearance of serum HBV DNA by the branched DNA assay or HBeAg during the follow-up period. The serum viral loads during and at the end of treatment were further determined by a quantitative real-time polymerase chain reaction assay.RESULTS: Relapse occurred in 6 (50.0%) HBeAg-negative patients within 12 mo post-treatment. Two relapsers had end-of-treatment serum viral load < 1 000 copies/mL, the proportion was not significantly different from that in the 6 non-relapsers (33.3% vs 16.7%; P = 1.00). Hepatitis B virus (HBV) DNA levels did not correlate with post-treatment relapse in HBeAg-positive patients either. However, genotype C patients tended to have a lower relapse rate than genotype B patients (14.3% vs57.9%, P= 0.08).CONCLUSION: Our results suggest that end-of-treatment virologic response cannot predict post-treatment relapse in patients with HBeAg-negative or -positive chronic hepatitis B. The impact of HBV genotype on the response to lamivudine treatment awaits further studies.展开更多
Hepatitis B virus (HBV) is a common viral pathogen that causes a substantial health burden worldwide. Remarkable progress has been made in our understanding of the natural stages of chronic HBV infection. A dynamic ba...Hepatitis B virus (HBV) is a common viral pathogen that causes a substantial health burden worldwide. Remarkable progress has been made in our understanding of the natural stages of chronic HBV infection. A dynamic balance between viral replication and host immune response is pivotal to the pathogenesis of liver disease. Knowledge of the HBV genome organization and replication cycle can unravel HBV genotypes and molecular variants, which contribute to the heterogeneity in outcome of chronic HBV infection. Most HBV infections are spontaneously resolved in immunocompetent adults, whereas they become chronic in most neonates and infants at a great risk of developing complications such as cirrhosis and hepatocellular carcinoma (HCC). Those with chronic HBV infection may present in one of the four phases of infection: immune tolerance, immune clearance [hepatitis B eantigen (HBeAg)-positive chronic hepatitis B (CHB)], inactive carrier state, and reactivation (HBeAg-negative CHB). Understanding the dynamic nature of chronic HBV infection is crucial in the management of HBV carriers. Long-term monitoring and optimal timing of antiviral therapy for chronic HBV infection help to prevent progression of HBV-related liver disease to its later stage, particularly in patients with higher risk markers of HCC, such as serum DNA concentration, HBeAg status, serum aminotransferase, HBV genotypes, and pre-core or core mutants.展开更多
文摘乙型肝炎病毒(hepatitis B virus,HBV)感染是一个严重的公共卫生问题。据世界卫生组织(World Health Organization,WHO)报道,全球60亿人口中,约20亿人曾感染过HBV,其中3.5亿人为慢性HBV感染,每年约有1 00万人死于HBV感染所致的肝衰竭、肝硬化和原发性肝细胞癌(肝癌)[1]。全球肝癌患者中,75%以上是HBV所致[2]。
文摘Chronic hepatitis B is one of the most common epidemic diseases in China and has become a majorhealth issue. To help standardize the prevention, diagnosis, and treatment of chronic hepatitis B, the Guideline on prevention and treatment of chronic hepatitis B （abbr. Guideline） was created by a group of appropriate experts belonging to the Society of Hepatology and the Society of Infectious Disease, the Chinese Medical Association according to the principles of evidence-based medicine using the latest clinical research data. The evidence used to formulate the recommendation has been classified into 3 classes and 5 grades, which are indicated by Roman numerals in brackets.
基金Supported by the Science Foundation of Guangdong Province,No. 99M04801G
文摘AIM: G1896A mutation in precore or A1762T/G1764Amutations in basal core promoter are suspected to be responsible for patients with detectable level of HBV DNA in serum after seroconversion from HBeAg to anti-Hbe. However, G1896A variant has impaired, while A1762T/ G1764A variant may have intact replication ability. They themselves or their coexistence status may play different roles in such meaningless seroconversion. For these reasons, the significances of these two types of mutations were comparatively investigated in this study. METHODS: One hundred and sixty-five sera with positive anti-Hbe and HBV DNA were collected from different patients. Mutations of G1896A and A1762T/G1764A among these serum samples were detected using competitively differentiated PCR. HBV DNA was demonstrated using real-time quantitative PCR. RESULTS: G1896A and/or A1762T/G1764A mutations were detected in 89.1% (147/165) out of patients with detectable HBV DNA in serum after HBeAg-to-anti-Hbe seroconversion. The positive rate of G1896A variants was significantly higher than that of A1762T/G1764A mutations (77.6% vs 50.3%, X2 = 26.61, P＜0.01). The coexistence positive rate of these two types of mutations was 38.8% (64/165). Coexistence mutations were found in 77.1% (64/83) out of sera with A1762T/G1764A mutations, and in 50.0% (64/128) out of sera with G1896A mutation. Compared with variants with G1896A mutation only, the coexistence mutations were predominant in patients with high level of serum HBV DNA, and related to higher total bilirubin, lower serum albumin and progressive liver diseases. CONCLUSION: The coexistence of G1896A mutation and A1762T/G1764A mutations is very common, and responsible for the major cases with high level of HBV DNA in serum and progressive liver diseases after HBeAg-to-anti-Hbe seroconversion. This coexistence mutation variant may have higher pathogenicity and replication ability.
文摘Hepatitis B virus （HBV） infection occurs primarily in hepatocytes in the liver with release of infectious virions and non-infectious empty surface antigen particles into the bloodstream. HBV replication is non-cytopathic. Transient infections run a course of several months, and chronic infections are often life-long. Chronic infections can lead to liver failure with cirrhosis and hepatocellniar carcinoma. It is generally accepted that neutralizing anti-HBs antibodies plays a key role in recovery from HBV infection by containing the spread of infection in the infected host and facilitating the removal and destruction of viral particles. However, the immune response initiated by the T-cell response to viral antigens is also important for viral clearance and disease pathogenesis in HBV infection. The three structural forms of the viral proteins, the HBsAg, the particulate HBcAg, and the nonparticulate HBeAg, may preferentially elicit different Th cell subsets. The different IgG subclass profiles of anti-HBs, anti-HBc, and anti-HBe in different HBV infection status were revealed. Moreover, the different IgG subclass profiles in chronic carriers did not change with different ALT and AST levels and may reflect the difference between stimulating antigens, immune response, and the stages of viral disease and provide the basis for the use of vaccines and prophylactic treatments for individuals at high risk of human HBV infection. This review elucidates the detailed understanding of the immune responses induced during transient and persistent infection, and the development of immunotherapy and immunodiagnosis in patients with HBV infection, and possible means of reducing the liver damage.
基金Supported by Grants From the Department of Health,the National Science Council,Executive Yuan,TaiwanNational Taiwan University Hospital (93S022)Liver Disease Prevention and Treatment Research Foundation,Taipei,Taiwan
文摘AIM: Attaining hepatitis B e antigen (HBeAg) seroconversion during lamivudine treatment is associated with fewer relapses in HBeAg-positive patients. In HBeAg-negative patients,predictors for post-treatment relapse remain largely unknown.We therefore studied whether end-of-treatment virologic response correlated with relapse after lamivudine treatment.METHODS: We prospectively analyzed 12 HBeAg-negative patients and 14 HBeAg-positive patients with chronic hepatitis B, who received at least 9 mo of lamivudine treatment and were followed up for 12 mo post-treatment. Relapse of hepatitis B activity was defined by an elevation of serum ALT level above twice the upper limit of normal as well as reappearance of serum HBV DNA by the branched DNA assay or HBeAg during the follow-up period. The serum viral loads during and at the end of treatment were further determined by a quantitative real-time polymerase chain reaction assay.RESULTS: Relapse occurred in 6 (50.0%) HBeAg-negative patients within 12 mo post-treatment. Two relapsers had end-of-treatment serum viral load < 1 000 copies/mL, the proportion was not significantly different from that in the 6 non-relapsers (33.3% vs 16.7%; P = 1.00). Hepatitis B virus (HBV) DNA levels did not correlate with post-treatment relapse in HBeAg-positive patients either. However, genotype C patients tended to have a lower relapse rate than genotype B patients (14.3% vs57.9%, P= 0.08).CONCLUSION: Our results suggest that end-of-treatment virologic response cannot predict post-treatment relapse in patients with HBeAg-negative or -positive chronic hepatitis B. The impact of HBV genotype on the response to lamivudine treatment awaits further studies.
基金Supported by Science and Technology Department of Qingdao Government 07-2-1-15-nsh
文摘Hepatitis B virus (HBV) is a common viral pathogen that causes a substantial health burden worldwide. Remarkable progress has been made in our understanding of the natural stages of chronic HBV infection. A dynamic balance between viral replication and host immune response is pivotal to the pathogenesis of liver disease. Knowledge of the HBV genome organization and replication cycle can unravel HBV genotypes and molecular variants, which contribute to the heterogeneity in outcome of chronic HBV infection. Most HBV infections are spontaneously resolved in immunocompetent adults, whereas they become chronic in most neonates and infants at a great risk of developing complications such as cirrhosis and hepatocellular carcinoma (HCC). Those with chronic HBV infection may present in one of the four phases of infection: immune tolerance, immune clearance [hepatitis B eantigen (HBeAg)-positive chronic hepatitis B (CHB)], inactive carrier state, and reactivation (HBeAg-negative CHB). Understanding the dynamic nature of chronic HBV infection is crucial in the management of HBV carriers. Long-term monitoring and optimal timing of antiviral therapy for chronic HBV infection help to prevent progression of HBV-related liver disease to its later stage, particularly in patients with higher risk markers of HCC, such as serum DNA concentration, HBeAg status, serum aminotransferase, HBV genotypes, and pre-core or core mutants.
