OBJECTIVE: To investigate the correlations between HBV DNA levels and viral antigen concentrations in patients with chronic hepatitis B and their significance in clinical practice. METHODS: The HBV DNA levels and sero...OBJECTIVE: To investigate the correlations between HBV DNA levels and viral antigen concentrations in patients with chronic hepatitis B and their significance in clinical practice. METHODS: The HBV DNA levels and serological markers of 118 patients with chronic hepatitis B and 87 patients with liver cirrhosis who had not been treated with antiviral drugs were determined as well as the other parameters relevant to liver function. RESULTS: The HBV DNA levels of the patients with chronic hepatitis anti cirrhosis were expressed as geometric mean±SD, 3.83×10~6±1.34 copies/ml anti 6.98×10~5±1.29 copies/ml, and their HBeAg concentrations expressed as the luminescent values rate of sample to control (s/co) were 35.40±1.26 and 4.05±1.28, respectively. The HBV DNA levels in HBeAg positive group were significantly higher than those in HBeAg negative group (P<0.0001). The correlation coefficient between HBV DNA level and HBeAg or HBsAg concentration was only O. 273 anti -0.12. During the recovery of hepatic function, the reduction of ALT or AST in patients with high viral content was significantly lower than that in patients with low viral content. No correlation was observed between HBV DNA and ALT levels. CONCLUSION: There are significant correlations between HBV DNA level anti HBeAg concentration, but the coefficient is lower. HBV DNA level is not significantly related to ALT, but it could affect the recovery of liver function.展开更多
On the basis of the successful establishment of an animal model in tree shrews experimentally in fected with human hepatitis B virus (HHBV), a study on the hepatocarcinogenic effects of HHBV and aflatoxin B1 (AFB1) by...On the basis of the successful establishment of an animal model in tree shrews experimentally in fected with human hepatitis B virus (HHBV), a study on the hepatocarcinogenic effects of HHBV and aflatoxin B1 (AFB1) by using this animal model was conducted through a lifelong experiment. Among 41 tree shrews exposed to AFB1, 17 were experimentally infected by HHBV and 24 were uninfected. After 158 weeks, significant difference of primary liver cancer (PLC) incidence was present between the HHBV infected (52.94%) and uninfected (12.5%) groups (p<0.05). No difference was found between these two groups in the amount of AFB4 ingestion. Moreover, 1/9 of the tree shrews infected only by HHBV but not exposed to AFB4 developed PLC. No PLC was found in 6 tree shrews that had neither been infected with HHBV nor been exposed to AFB4. These results suggest the possible etiologic relationship between HHBV infection and PLC, as well as the synergetic effects of HHBV and AFB4 during PLC development.展开更多
BACKGROUND:Continuous lamivudine therapy is associated with high rates of YMDD mutations,which are the main causes of drug resistance.The current study explores the association of the emergence of YMDD mutations with ...BACKGROUND:Continuous lamivudine therapy is associated with high rates of YMDD mutations,which are the main causes of drug resistance.The current study explores the association of the emergence of YMDD mutations with pretherapy HBV genotype,HBV-DNA levels,HBeAg status,and serum alanine aminotransferase(ALT) levels in Chinese patients receiving lamivudine therapy for chronic hepatitis B.METHODS:A total of 319 chronic hepatitis B patients who received lamivudine therapy for more than a year were enrolled in this study.YMDD mutations,HBV genotype,HBV-DNA levels,HBeAg status,and ALT levels were determined prior to their lamivudine treatment and every three months for a year of this therapy.RESULTS:Among the 319 patients,137(42.95%) were infected with genotype B and 182(57.05%) with genotype C.Up to 94 patients(29.47%) developed YMDD mutations within one year of lamivudine therapy.Furthermore,50 patients with HBV genotype B and 44 patients with genotype C developed YMDD mutations(36.50% vs 24.18%,P<0.05).Logistic regression analysis showed that pretherapy HBV genotype,HBV-DNA levels,and HBeAg status are independent factors for the emergence of YMDD mutations(HBV genotype:OR=2.159,95% CI 1.291-3.609,P=0.003;HBV-DNA:OR=1.653,95% CI 1.231-2.218,P=0.001;HBeAg:OR=2.021,95% CI 1.201-3.399,P=0.008).CONCLUSIONS:HBV genotype,HBV-DNA levels,and HBeAg status at baseline are the independent factors associated with the emergence of YMDD mutations among Chinese patients receiving lamivudine therapy for chronic hepatitis B.These findings are helpful to the development of therapeutic strategies for these patients.展开更多
Little has been learnt in the last 30 years about detection of HBV genome as well as its mutation analysis between hepatitis B fathers (HBF) and their children. In this study, we used nest polymerase chain reaction ...Little has been learnt in the last 30 years about detection of HBV genome as well as its mutation analysis between hepatitis B fathers (HBF) and their children. In this study, we used nest polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), and DNA sequencing analysis, to examine the integrated HBV genome in paraffin-embedded testis tissues, which were taken as samples from HBE and in peripheral blood mononuclear cells (PBMC) from 74 cases of HBFs and their children who were born after their fathers' HBV infection (caHBF). We found that HBV DNA existed in testis tissues, mainly in the basilar parts of the seminiferous tubules, and also in PBMC of HBE It was also documented that there were point mutations of poly-loci, insertions and deletions of nucleotides in integrated HBV genomes, and the types of gene mutations in the HBFs were similar to those in caHBE This study addresses the major types of gene mutations in integrated HBV genome in human patients and also presents reliable evidence of possible genetic transmission of hepatitis B.展开更多
Hepatitis associated anti-tuberculous treatment(HATT) has been a main obstacle in managing patients co-infected with Mycobacterium tuberculosis and hepatitis B virus(HBV). Therefore, we evaluated the factors relat...Hepatitis associated anti-tuberculous treatment(HATT) has been a main obstacle in managing patients co-infected with Mycobacterium tuberculosis and hepatitis B virus(HBV). Therefore, we evaluated the factors related to the severity of adverse effects during HATT, especially those associated with liver failure. A retrospective study was carried out at Tongji Hospital from 2007 to 2012. Increases in serum transaminase levels of 〉3, 5, and 10 times the upper limit of normal(ULN) were used to define liver damage as mild, moderate, and severe, respectively. Patients with elevated total bilirubin(TBil) levels that were more than 10 times the ULN(〉171 μmol/L) with or without decreased(〈40%) prothrombin activity(PTA) were diagnosed with liver failure. A cohort of 87 patients was analyzed. The incidence of liver damage and liver failure was 59.8%(n=52) and 25.3%(n=22), respectively. The following variables were correlated with the severity of hepatotoxicity: albumin(ALB) levels, PTA, platelet counts(PLT), and the use of antiretroviral therapies(P〈0.05). Hypo-proteinemia and antiretroviral therapy were significantly associated with liver failure, and high viral loads were a significant risk factor with an odds ratio(OR) of 2.066. Judicious follow-up of clinical conditions, liver function tests, and coagulation function, especially in patients with high HBV loads and hypoalbuminemia is recommended. It may be advisable to reconsider the use of antiviral drugs failure during the course of anti-tuberculous treatment of HBV infection patients to avoid the occurrence of furious liver failure.展开更多
Objective The clinical significance of differential distribution of hepatitis B virus(HBV)nucleocapsid antigen in hepatocytes remains unknown.The goal of this study is to determine the relationship between distinct HB...Objective The clinical significance of differential distribution of hepatitis B virus(HBV)nucleocapsid antigen in hepatocytes remains unknown.The goal of this study is to determine the relationship between distinct HBV core antigen distribution pattern and alanine transaminase(ALT),liver histological inflammatory activity grades,serum HBeAg status and HBV DNA level.Methods Total of 958 cases with chronic hepatitis B were recruited into this study.Liver function tests,serum HBV DNA level,serological HBV markers and liver immunohistochemistry were examined according to the conventional instructions.Chi Square tests were performed to analyze the differences among these groups.Results It was found that 552(58%)cases were tested positive for HBV core antigen by immunohistochemical staining.Cytoplasmic hepatitis B core antigen(HBcAg)expression correlated with ALT level and serum HBV DNA and liver inflammatory activity scores,however,nuclear HBcAg expression in hepatocytes was associated with normal ALT level,lower liver inflammatory activity score and higher serum HBV DNA level and rate of HBeAg positivity.Both nuclear and cytoplasmic HBcAg expression in hepatocytes associated with a middle ALT level and liver inflammatory activity score,higher rate of serum detectable HBeAg and a higher HBV DNA level.However,undetectable core antigen was related to a lower ALT level and histological inflammatory activity grade,lower positive HBeAg rate and HBV DNA level.Conclusions Undetectable liver HBcAg is associated with HBV clearance,ALT normalization and hepatitis B e antigen(HBeAg)seroconversion,and cytoplasmic HBcAg expression associated with higher hepatic inflammatory activity.However,nuclear HBcAg expression correlates with immune tolerance characterized with normal ALT and lower liver inflammatory activity,higher HBV replication level and higher rate of HBeAg positivity.展开更多
In this study, the anti-HBV effects of tea polyphenols (TP) were examined. After cells were exposed to TP for 3, 6, 9 days, amounts of HBsAg, HBeAg and HBV-DNA released into the supernatant of the cultured HepG2 2.2...In this study, the anti-HBV effects of tea polyphenols (TP) were examined. After cells were exposed to TP for 3, 6, 9 days, amounts of HBsAg, HBeAg and HBV-DNA released into the supernatant of the cultured HepG2 2.2.15 cells were detected. TP, to some extent, inhibited the secretion of HBsAg and strongly suppressed the secretion of HBeAg in a dose-dependent (P〈0.01) and time-dependent manner, with 50% maximal inhibitory concentration (IC50) value being 7.34μg/mL on the 9th day, but the time-dependence was not significant (P=0.051). Expression of HBV-DNA in the supernatant of the cell culture also was significantly decreased in a dose-dependent fashion (P〈0.01). The ICS0 of TP in inhibiting HBV DNA was 2.54 pg/mL. It concluded that TP possessed potential anti-HBV effects and may be used as a treatment alternative for HBV infection.展开更多
Summary: Recently, suppressor of cytokine signaling-3 (SOCS3) has been shown to be an inducible endogenous negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway ...Summary: Recently, suppressor of cytokine signaling-3 (SOCS3) has been shown to be an inducible endogenous negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway which is relevant in inflammatory response, while its functions in acute liver failure and HBV-induced acute-on-chronic liver failure (HBV-ACLF) have not been fully elucidated. In this study, we explored the role of SOCS3 in the development of mouse hepatitis virus strain 3 (MHV-3)-induced acute liver failure and its expression in liver and peripheral blood mononuclear cells (PBMCs) of patients with HBV-ACLF. Inflammation-related gene expression was detected by real-time PCR, immtmohistochemistry and Western blotting. The correlation between SOCS3 level and liver injury was studied. Our results showed that the SOCS3 expression was significantly elevated in both the liver tissue and PBMCs from patients with HBV-ACLF compared to mild chronic hepatitis B (CHB). Moreover, a time course study showed that SOCS3 level was increased remarkably in the liver of BALB/cJ mice at 72 h post-infection. Pro-inflammatory cytokines, interleukin (IL)-1 β, IL-6, and tumor necrosis factor (TNF)-α, were also increased significantly at 72 h post-infection. There was a close correlation between hepatic SOCS3 level and IL-6, and the severity of liver injury defined by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respectively. These data suggested that SOCS3 may play a pivotal role in the pathogenesis of MHV-3-induced acute liver failure and HBV-ACLF.展开更多
The global burden of hepatitis B virus(HBV)and hepatitis C virus(HCV)infections and coinfection represents a major public health concern,particularly in resource-limited settings.Elimination of HCV by 2030 has become ...The global burden of hepatitis B virus(HBV)and hepatitis C virus(HCV)infections and coinfection represents a major public health concern,particularly in resource-limited settings.Elimination of HCV by 2030 has become foreseeable,with effective direct-acting antiviral oral therapies and the availability of affordable generics in low-and-middle-income countries(LMICs).However,access to oral nucleos(t)ide therapy for HBV remains critical and is limited outside the existing global HIV program platforms despite affordable prices.Prevention of mother-to-child transmission of HBV through scaling up of birth dose implementation in LMICs is essential to achieve the 2030 elimination goal.Most individuals living with HBV and/or HCV in resource-limited settings are unaware of their infection,and with improved access to medications,the most significant barrier remains access to affordable diagnostics and preventive strategies.The coronavirus disease 2019 pandemic interrupted hepatitis elimination programs,albeit offered opportunities for improved diagnostic capacities and raised political awareness of the critical need for strengthening health care services and universal health coverage.This review underpins the HBV and HCV management challenges in resource-limited settings,highlighting the current status and suggested future elimination strategies in some of these countries.Global efforts should continue to improve awareness and political commitment.Financial resources should be secured to access and implement comprehensive strategies for diagnosis and linkage to care in resource-constrained settings to fulfill the 2030 elimination goal.展开更多
Objective To assess on-treatment serum HBsAg and HBV DNA kinetics in HBeAg-positive CHB patients to predict the efficacy of pegylated interferon(PEG-IFN) in early phase of treatment. Methods Forty-one treatment-naive ...Objective To assess on-treatment serum HBsAg and HBV DNA kinetics in HBeAg-positive CHB patients to predict the efficacy of pegylated interferon(PEG-IFN) in early phase of treatment. Methods Forty-one treatment-naive HBeAg-positive patients treated with PEG-IFNα 2a at a dose of 180 μg/week for at least 24 weeks were evaluated. Their treatment response was assessed, including normalization of serum ALT, decline of serum HBV DNA and loss of HBeAg. Results We found that a decrease of HBV DNA level at the 4th week was positively correlated with the decrease of HBV DNA level at the 12th week and 24th week(r = 0.8202, P < 0.0001 and r = 0.6838, P < 0.0001, respectively). We observed that a decrease of HBsAg level at the 4th week was positively correlated with decrease of HBsAg level at the 12th week and 24th week(r = 0.4868, P = 0.0023 and r = 0.4251, P = 0.0109, respectively). A decrease of HBsAg level at the 24th week was positively correlated with the decrease of HBV DNA level at the 24th week(r = 0.5262, P = 0.0024). Serum level of IFN and IFN neutralizing antibody had no relationship with HBV DNA or HBsAg titers kinetics. Conclusions The decline of serum HBV DNA and hepatitis B surface antigen at the 4th week can be used to predict the response to PEG-IFNα 2a in patients with HBeAg positive chronic hepatitis B.展开更多
AIM: To identify the factors associated with virologic breakthrough and to select a subgroup of patients who respond well to lamivudine without developing virologic breakthrough (VBT). METHODS: Of 79 patients who had ...AIM: To identify the factors associated with virologic breakthrough and to select a subgroup of patients who respond well to lamivudine without developing virologic breakthrough (VBT). METHODS: Of 79 patients who had received lamivudine therapy for 9-57 mo, 34 were HBeAg-positive and 45 were HBeAg-negative, 24 developed virologic breakthrough and 55 did not. Clinical and virologic factors were compared between the two groups. RESULTS: The median duration of therapy was 25 (9-57) mo. Virologic breakthrough was defined as a > 1 log HBV DNA increase following initial suppression. When several factors, including gender, duration of infection, baseline HBV DNA, and baseline ALT in HBeAg-positive chronic hepatitis patients were analyzed by logistic regression, the most important predictor of virologic breakthrough was the baseline HBV DNA (r2 = 0.12, P < 0.05). When HBeAg-postitive chronic hepatitis patients were divided into two groups by a point of 6.6 log HBV DNA, the incidence of virologic breakthough between two groups was significantly different. CONCLUSION: Lamivudine may remain an effective first line therapy for those HBeAg-positive patients with a baseline HBV DNA < 6.6 log10 copies/mL.展开更多
AIM: To investigate the influence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B. METHODS: HLA-DRB1*03, *07, *09, *12, *15 alleles were determined using polymerase chain reactio...AIM: To investigate the influence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B. METHODS: HLA-DRB1*03, *07, *09, *12, *15 alleles were determined using polymerase chain reaction/sequence specific primer (PCR/SSP) technique in 126 patients with chronic hepatitis B and 76 normal control subjects in Shandong Province, and HBV genotypes were determined by nested-PCR analysis using type-specific primers in 126 patients. RESULTS: The positivity of HLA-DRB1*07 allele in chronic hepatitis B group was significantly higher than that in normal control group (X2=6.33, P<0.025, RR=2.37). Among the 126 patients, genotype B was found in 38 (30.2%), genotype C in 69 (54.8%), and mixed genotype (B+C) in 19 (15.0%), genotypes D-F were not found. Among the 46 DRB1*07(+) patients, 7 were responders and 39 were non-responders among them (X2=6.71, P<0.05). The positivity of HLA-DRB1*07 and prevalence of HBV genotype C were significantly higher in non-responders than in responders. CONCLUSION: High positivities of HLA-DRBI *07 allele and HBV genotype C are closely associated with the lower response to interferon-α therapy for chronic hepatitis B.展开更多
Objectives: To evaluate the inhibitory effect mediated by combination of small interfering RNAs (siRNAs) targeting different sites of hepatitis B virus (HBV) transcripts on the viral replication and antigen expression...Objectives: To evaluate the inhibitory effect mediated by combination of small interfering RNAs (siRNAs) targeting different sites of hepatitis B virus (HBV) transcripts on the viral replication and antigen expression in vitro. Methods: (1) Seven siRNAs targeting surface (S), polymerase (P) or precore (PreC) region of HBV genome were designed and chemically synthesized. (2) HBV-producing HepG2.2.15 cells were treated with or without siRNAs for 72 h. (3) HBsAg and HBeAg in the cell culture medium were detected by enzyme-linked immunoadsorbent assay. (4) Intracellular viral DNA was quantified by real-time PCR (Polymerase Chain Reaction). (5) HBV viral mRNA was reverse transcribed and quantified by real-time PCR. (6) The change of cell cycle and apoptosis was determined by flow cytometry. Results: Our data demonstrated that synthetic small interfering RNAs (siRNAs) targeting S and PreC gene could efficiently and specifically inhibit HBV replication and antigen expression. The ex- pression of HBsAg and HBeAg and the replication of HBV could be specifically inhibited in a dose-dependent manner by siRNAs. Furthermore, our results showed that the combination of siRNAs targeting various regions could inhibit HBV replication and antigen expression in a more efficient way than the use of single siRNA at the same final concentration. No apoptotic change was observed in the cell after siRNA treatment. Conclusion: Our results demonstrated that siRNAs exerted robust and specific inhibi- tion on HBV replication and antigen expression in a cell culture system and combination of siRNAs targeting different regions exhibited more potency.展开更多
AIM: To clarify differences in antiviral effect of the drug in patients with different ALT levels, we examined the changes in HBV markers in patients with high or low ALT levels with or without lamivudine treatment. M...AIM: To clarify differences in antiviral effect of the drug in patients with different ALT levels, we examined the changes in HBV markers in patients with high or low ALT levels with or without lamivudine treatment. METHODS: Thirty-seven HBeAg-positive patients were studied. Ten patients with ALT levels higher than 200 IU/L (group 1) and 8 patients with ALT below 200 IU/L (group 2) were treated orally with 100 mg/d of lamivudine. As untreated control, 9 patients with ALT above 200 IU/L (group 3) and 10 patients with ALT below 200 IU/L (group 4) were examined. ALT level, HBeAg/HBeAb status, and HBV DNA level were examined monthly for 11.9±0.4 mo.RESULTS: The ALT level normalized in all 10 patients of group 1, 7/8 of group 2, 4/9 of group 3, and 1/10 of group 4 within 6 mo (groups 1 vs 2, P = NS; groups 1 vs 3, P = 0.002; groups 1vs 4, P<0.0001). HBV DNA fell below the detection limit in all 10 patients of group 1, 7/8 of group 2, 0/9 of group 3, and 0/10 of group 4 within 6 mo (groups 1 vs 2, P = NS). HBeAg became seronegative in 7/10 patients of group 1, 1/8 of group 2, 3/9 of group 3, and 0/10 of group 4 within 12 mo (groups 1 vs2, P= 0.02;groups 1 vs 3, P = NS).CONCLUSION: Our data suggest that HBeAg-positive patients with higher ALT levels can be considered good candidates for lamivudine therapy, probably because lamivudine accelerates the natural seroconversion of HBeAg, accompanied by HBV DNA loss, in these patients.展开更多
Naturally occurring mutations in surface proteins of Hepatitis B virus(HBV) usually result in altered hepatitis B surface antigen(HBsAg) secretion efficiency.In the present study,we reported two conserved residues,M75...Naturally occurring mutations in surface proteins of Hepatitis B virus(HBV) usually result in altered hepatitis B surface antigen(HBsAg) secretion efficiency.In the present study,we reported two conserved residues,M75 and M103 with respect to HBsAg,mutations of which not only attenuated HBsAg secretion(M75 only),but also suppressed HBV genome replication without compromising the overlapping p-gene product.We also found M75 and M103 can initiate truncated surface protein(TSPs) synthesis upon over-expression of full-length surface proteins,which may possibly contribute to HBV genome replication.However,attempts to rescue replicationdefective HBV mutant by co-expression of TSPs initiated from M75 or M103 were unsuccessful,which indicated surface proteins rather than the putative TSPs were involved in regulation of HBV genome replication.展开更多
文摘OBJECTIVE: To investigate the correlations between HBV DNA levels and viral antigen concentrations in patients with chronic hepatitis B and their significance in clinical practice. METHODS: The HBV DNA levels and serological markers of 118 patients with chronic hepatitis B and 87 patients with liver cirrhosis who had not been treated with antiviral drugs were determined as well as the other parameters relevant to liver function. RESULTS: The HBV DNA levels of the patients with chronic hepatitis anti cirrhosis were expressed as geometric mean±SD, 3.83×10~6±1.34 copies/ml anti 6.98×10~5±1.29 copies/ml, and their HBeAg concentrations expressed as the luminescent values rate of sample to control (s/co) were 35.40±1.26 and 4.05±1.28, respectively. The HBV DNA levels in HBeAg positive group were significantly higher than those in HBeAg negative group (P<0.0001). The correlation coefficient between HBV DNA level and HBeAg or HBsAg concentration was only O. 273 anti -0.12. During the recovery of hepatic function, the reduction of ALT or AST in patients with high viral content was significantly lower than that in patients with low viral content. No correlation was observed between HBV DNA and ALT levels. CONCLUSION: There are significant correlations between HBV DNA level anti HBeAg concentration, but the coefficient is lower. HBV DNA level is not significantly related to ALT, but it could affect the recovery of liver function.
文摘On the basis of the successful establishment of an animal model in tree shrews experimentally in fected with human hepatitis B virus (HHBV), a study on the hepatocarcinogenic effects of HHBV and aflatoxin B1 (AFB1) by using this animal model was conducted through a lifelong experiment. Among 41 tree shrews exposed to AFB1, 17 were experimentally infected by HHBV and 24 were uninfected. After 158 weeks, significant difference of primary liver cancer (PLC) incidence was present between the HHBV infected (52.94%) and uninfected (12.5%) groups (p<0.05). No difference was found between these two groups in the amount of AFB4 ingestion. Moreover, 1/9 of the tree shrews infected only by HHBV but not exposed to AFB4 developed PLC. No PLC was found in 6 tree shrews that had neither been infected with HHBV nor been exposed to AFB4. These results suggest the possible etiologic relationship between HHBV infection and PLC, as well as the synergetic effects of HHBV and AFB4 during PLC development.
文摘BACKGROUND:Continuous lamivudine therapy is associated with high rates of YMDD mutations,which are the main causes of drug resistance.The current study explores the association of the emergence of YMDD mutations with pretherapy HBV genotype,HBV-DNA levels,HBeAg status,and serum alanine aminotransferase(ALT) levels in Chinese patients receiving lamivudine therapy for chronic hepatitis B.METHODS:A total of 319 chronic hepatitis B patients who received lamivudine therapy for more than a year were enrolled in this study.YMDD mutations,HBV genotype,HBV-DNA levels,HBeAg status,and ALT levels were determined prior to their lamivudine treatment and every three months for a year of this therapy.RESULTS:Among the 319 patients,137(42.95%) were infected with genotype B and 182(57.05%) with genotype C.Up to 94 patients(29.47%) developed YMDD mutations within one year of lamivudine therapy.Furthermore,50 patients with HBV genotype B and 44 patients with genotype C developed YMDD mutations(36.50% vs 24.18%,P<0.05).Logistic regression analysis showed that pretherapy HBV genotype,HBV-DNA levels,and HBeAg status are independent factors for the emergence of YMDD mutations(HBV genotype:OR=2.159,95% CI 1.291-3.609,P=0.003;HBV-DNA:OR=1.653,95% CI 1.231-2.218,P=0.001;HBeAg:OR=2.021,95% CI 1.201-3.399,P=0.008).CONCLUSIONS:HBV genotype,HBV-DNA levels,and HBeAg status at baseline are the independent factors associated with the emergence of YMDD mutations among Chinese patients receiving lamivudine therapy for chronic hepatitis B.These findings are helpful to the development of therapeutic strategies for these patients.
基金This study was supported by the National Natural Science Foundation of China(No.3870310)the National Natural Science Foundation of Shandong Province(No.91C0125).The authors are indebted to Associate Professor Linxiang Guo for his critical reading of this manuscript.
文摘Little has been learnt in the last 30 years about detection of HBV genome as well as its mutation analysis between hepatitis B fathers (HBF) and their children. In this study, we used nest polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), and DNA sequencing analysis, to examine the integrated HBV genome in paraffin-embedded testis tissues, which were taken as samples from HBE and in peripheral blood mononuclear cells (PBMC) from 74 cases of HBFs and their children who were born after their fathers' HBV infection (caHBF). We found that HBV DNA existed in testis tissues, mainly in the basilar parts of the seminiferous tubules, and also in PBMC of HBE It was also documented that there were point mutations of poly-loci, insertions and deletions of nucleotides in integrated HBV genomes, and the types of gene mutations in the HBFs were similar to those in caHBE This study addresses the major types of gene mutations in integrated HBV genome in human patients and also presents reliable evidence of possible genetic transmission of hepatitis B.
基金supported in part by the Organization Department of the Central Committee of the Communist Party of China 2015“sunshine of the west”visiting scholar program(No.2903)
文摘Hepatitis associated anti-tuberculous treatment(HATT) has been a main obstacle in managing patients co-infected with Mycobacterium tuberculosis and hepatitis B virus(HBV). Therefore, we evaluated the factors related to the severity of adverse effects during HATT, especially those associated with liver failure. A retrospective study was carried out at Tongji Hospital from 2007 to 2012. Increases in serum transaminase levels of 〉3, 5, and 10 times the upper limit of normal(ULN) were used to define liver damage as mild, moderate, and severe, respectively. Patients with elevated total bilirubin(TBil) levels that were more than 10 times the ULN(〉171 μmol/L) with or without decreased(〈40%) prothrombin activity(PTA) were diagnosed with liver failure. A cohort of 87 patients was analyzed. The incidence of liver damage and liver failure was 59.8%(n=52) and 25.3%(n=22), respectively. The following variables were correlated with the severity of hepatotoxicity: albumin(ALB) levels, PTA, platelet counts(PLT), and the use of antiretroviral therapies(P〈0.05). Hypo-proteinemia and antiretroviral therapy were significantly associated with liver failure, and high viral loads were a significant risk factor with an odds ratio(OR) of 2.066. Judicious follow-up of clinical conditions, liver function tests, and coagulation function, especially in patients with high HBV loads and hypoalbuminemia is recommended. It may be advisable to reconsider the use of antiviral drugs failure during the course of anti-tuberculous treatment of HBV infection patients to avoid the occurrence of furious liver failure.
文摘Objective The clinical significance of differential distribution of hepatitis B virus(HBV)nucleocapsid antigen in hepatocytes remains unknown.The goal of this study is to determine the relationship between distinct HBV core antigen distribution pattern and alanine transaminase(ALT),liver histological inflammatory activity grades,serum HBeAg status and HBV DNA level.Methods Total of 958 cases with chronic hepatitis B were recruited into this study.Liver function tests,serum HBV DNA level,serological HBV markers and liver immunohistochemistry were examined according to the conventional instructions.Chi Square tests were performed to analyze the differences among these groups.Results It was found that 552(58%)cases were tested positive for HBV core antigen by immunohistochemical staining.Cytoplasmic hepatitis B core antigen(HBcAg)expression correlated with ALT level and serum HBV DNA and liver inflammatory activity scores,however,nuclear HBcAg expression in hepatocytes was associated with normal ALT level,lower liver inflammatory activity score and higher serum HBV DNA level and rate of HBeAg positivity.Both nuclear and cytoplasmic HBcAg expression in hepatocytes associated with a middle ALT level and liver inflammatory activity score,higher rate of serum detectable HBeAg and a higher HBV DNA level.However,undetectable core antigen was related to a lower ALT level and histological inflammatory activity grade,lower positive HBeAg rate and HBV DNA level.Conclusions Undetectable liver HBcAg is associated with HBV clearance,ALT normalization and hepatitis B e antigen(HBeAg)seroconversion,and cytoplasmic HBcAg expression associated with higher hepatic inflammatory activity.However,nuclear HBcAg expression correlates with immune tolerance characterized with normal ALT and lower liver inflammatory activity,higher HBV replication level and higher rate of HBeAg positivity.
基金supported by a grant from the R&D Department of Hubei Province (No.2007B07)
文摘In this study, the anti-HBV effects of tea polyphenols (TP) were examined. After cells were exposed to TP for 3, 6, 9 days, amounts of HBsAg, HBeAg and HBV-DNA released into the supernatant of the cultured HepG2 2.2.15 cells were detected. TP, to some extent, inhibited the secretion of HBsAg and strongly suppressed the secretion of HBeAg in a dose-dependent (P〈0.01) and time-dependent manner, with 50% maximal inhibitory concentration (IC50) value being 7.34μg/mL on the 9th day, but the time-dependence was not significant (P=0.051). Expression of HBV-DNA in the supernatant of the cell culture also was significantly decreased in a dose-dependent fashion (P〈0.01). The ICS0 of TP in inhibiting HBV DNA was 2.54 pg/mL. It concluded that TP possessed potential anti-HBV effects and may be used as a treatment alternative for HBV infection.
基金supported by the grants from the National Science Foundation of China Advanced Program(No.NSFC81171558,NSFC81271808 and NSFC81030007)Innovation Team Development Plan of the Ministry of Education of China[No.IRT1131(2011)]National Twelfth-Five Years Project in Science and Technology of China(No.2013ZX10002-003)
文摘Summary: Recently, suppressor of cytokine signaling-3 (SOCS3) has been shown to be an inducible endogenous negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway which is relevant in inflammatory response, while its functions in acute liver failure and HBV-induced acute-on-chronic liver failure (HBV-ACLF) have not been fully elucidated. In this study, we explored the role of SOCS3 in the development of mouse hepatitis virus strain 3 (MHV-3)-induced acute liver failure and its expression in liver and peripheral blood mononuclear cells (PBMCs) of patients with HBV-ACLF. Inflammation-related gene expression was detected by real-time PCR, immtmohistochemistry and Western blotting. The correlation between SOCS3 level and liver injury was studied. Our results showed that the SOCS3 expression was significantly elevated in both the liver tissue and PBMCs from patients with HBV-ACLF compared to mild chronic hepatitis B (CHB). Moreover, a time course study showed that SOCS3 level was increased remarkably in the liver of BALB/cJ mice at 72 h post-infection. Pro-inflammatory cytokines, interleukin (IL)-1 β, IL-6, and tumor necrosis factor (TNF)-α, were also increased significantly at 72 h post-infection. There was a close correlation between hepatic SOCS3 level and IL-6, and the severity of liver injury defined by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respectively. These data suggested that SOCS3 may play a pivotal role in the pathogenesis of MHV-3-induced acute liver failure and HBV-ACLF.
文摘The global burden of hepatitis B virus(HBV)and hepatitis C virus(HCV)infections and coinfection represents a major public health concern,particularly in resource-limited settings.Elimination of HCV by 2030 has become foreseeable,with effective direct-acting antiviral oral therapies and the availability of affordable generics in low-and-middle-income countries(LMICs).However,access to oral nucleos(t)ide therapy for HBV remains critical and is limited outside the existing global HIV program platforms despite affordable prices.Prevention of mother-to-child transmission of HBV through scaling up of birth dose implementation in LMICs is essential to achieve the 2030 elimination goal.Most individuals living with HBV and/or HCV in resource-limited settings are unaware of their infection,and with improved access to medications,the most significant barrier remains access to affordable diagnostics and preventive strategies.The coronavirus disease 2019 pandemic interrupted hepatitis elimination programs,albeit offered opportunities for improved diagnostic capacities and raised political awareness of the critical need for strengthening health care services and universal health coverage.This review underpins the HBV and HCV management challenges in resource-limited settings,highlighting the current status and suggested future elimination strategies in some of these countries.Global efforts should continue to improve awareness and political commitment.Financial resources should be secured to access and implement comprehensive strategies for diagnosis and linkage to care in resource-constrained settings to fulfill the 2030 elimination goal.
基金supported by Major Science and Technology Special Project of China Eleventh Five-year Plan(2008ZX10002-004)Major Science and Technology Special Project of China Twelfth Five-year Plan (2012ZX10002003)Natural Science Foundation of China (81101240) to NL
文摘Objective To assess on-treatment serum HBsAg and HBV DNA kinetics in HBeAg-positive CHB patients to predict the efficacy of pegylated interferon(PEG-IFN) in early phase of treatment. Methods Forty-one treatment-naive HBeAg-positive patients treated with PEG-IFNα 2a at a dose of 180 μg/week for at least 24 weeks were evaluated. Their treatment response was assessed, including normalization of serum ALT, decline of serum HBV DNA and loss of HBeAg. Results We found that a decrease of HBV DNA level at the 4th week was positively correlated with the decrease of HBV DNA level at the 12th week and 24th week(r = 0.8202, P < 0.0001 and r = 0.6838, P < 0.0001, respectively). We observed that a decrease of HBsAg level at the 4th week was positively correlated with decrease of HBsAg level at the 12th week and 24th week(r = 0.4868, P = 0.0023 and r = 0.4251, P = 0.0109, respectively). A decrease of HBsAg level at the 24th week was positively correlated with the decrease of HBV DNA level at the 24th week(r = 0.5262, P = 0.0024). Serum level of IFN and IFN neutralizing antibody had no relationship with HBV DNA or HBsAg titers kinetics. Conclusions The decline of serum HBV DNA and hepatitis B surface antigen at the 4th week can be used to predict the response to PEG-IFNα 2a in patients with HBeAg positive chronic hepatitis B.
基金Supported by the research grant of the Chungbuk National University in 2004
文摘AIM: To identify the factors associated with virologic breakthrough and to select a subgroup of patients who respond well to lamivudine without developing virologic breakthrough (VBT). METHODS: Of 79 patients who had received lamivudine therapy for 9-57 mo, 34 were HBeAg-positive and 45 were HBeAg-negative, 24 developed virologic breakthrough and 55 did not. Clinical and virologic factors were compared between the two groups. RESULTS: The median duration of therapy was 25 (9-57) mo. Virologic breakthrough was defined as a > 1 log HBV DNA increase following initial suppression. When several factors, including gender, duration of infection, baseline HBV DNA, and baseline ALT in HBeAg-positive chronic hepatitis patients were analyzed by logistic regression, the most important predictor of virologic breakthrough was the baseline HBV DNA (r2 = 0.12, P < 0.05). When HBeAg-postitive chronic hepatitis patients were divided into two groups by a point of 6.6 log HBV DNA, the incidence of virologic breakthough between two groups was significantly different. CONCLUSION: Lamivudine may remain an effective first line therapy for those HBeAg-positive patients with a baseline HBV DNA < 6.6 log10 copies/mL.
文摘AIM: To investigate the influence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B. METHODS: HLA-DRB1*03, *07, *09, *12, *15 alleles were determined using polymerase chain reaction/sequence specific primer (PCR/SSP) technique in 126 patients with chronic hepatitis B and 76 normal control subjects in Shandong Province, and HBV genotypes were determined by nested-PCR analysis using type-specific primers in 126 patients. RESULTS: The positivity of HLA-DRB1*07 allele in chronic hepatitis B group was significantly higher than that in normal control group (X2=6.33, P<0.025, RR=2.37). Among the 126 patients, genotype B was found in 38 (30.2%), genotype C in 69 (54.8%), and mixed genotype (B+C) in 19 (15.0%), genotypes D-F were not found. Among the 46 DRB1*07(+) patients, 7 were responders and 39 were non-responders among them (X2=6.71, P<0.05). The positivity of HLA-DRB1*07 and prevalence of HBV genotype C were significantly higher in non-responders than in responders. CONCLUSION: High positivities of HLA-DRBI *07 allele and HBV genotype C are closely associated with the lower response to interferon-α therapy for chronic hepatitis B.
基金Project (No. 30471943) supported partly by the National Natural Science Foundation of China
文摘Objectives: To evaluate the inhibitory effect mediated by combination of small interfering RNAs (siRNAs) targeting different sites of hepatitis B virus (HBV) transcripts on the viral replication and antigen expression in vitro. Methods: (1) Seven siRNAs targeting surface (S), polymerase (P) or precore (PreC) region of HBV genome were designed and chemically synthesized. (2) HBV-producing HepG2.2.15 cells were treated with or without siRNAs for 72 h. (3) HBsAg and HBeAg in the cell culture medium were detected by enzyme-linked immunoadsorbent assay. (4) Intracellular viral DNA was quantified by real-time PCR (Polymerase Chain Reaction). (5) HBV viral mRNA was reverse transcribed and quantified by real-time PCR. (6) The change of cell cycle and apoptosis was determined by flow cytometry. Results: Our data demonstrated that synthetic small interfering RNAs (siRNAs) targeting S and PreC gene could efficiently and specifically inhibit HBV replication and antigen expression. The ex- pression of HBsAg and HBeAg and the replication of HBV could be specifically inhibited in a dose-dependent manner by siRNAs. Furthermore, our results showed that the combination of siRNAs targeting various regions could inhibit HBV replication and antigen expression in a more efficient way than the use of single siRNA at the same final concentration. No apoptotic change was observed in the cell after siRNA treatment. Conclusion: Our results demonstrated that siRNAs exerted robust and specific inhibi- tion on HBV replication and antigen expression in a cell culture system and combination of siRNAs targeting different regions exhibited more potency.
文摘AIM: To clarify differences in antiviral effect of the drug in patients with different ALT levels, we examined the changes in HBV markers in patients with high or low ALT levels with or without lamivudine treatment. METHODS: Thirty-seven HBeAg-positive patients were studied. Ten patients with ALT levels higher than 200 IU/L (group 1) and 8 patients with ALT below 200 IU/L (group 2) were treated orally with 100 mg/d of lamivudine. As untreated control, 9 patients with ALT above 200 IU/L (group 3) and 10 patients with ALT below 200 IU/L (group 4) were examined. ALT level, HBeAg/HBeAb status, and HBV DNA level were examined monthly for 11.9±0.4 mo.RESULTS: The ALT level normalized in all 10 patients of group 1, 7/8 of group 2, 4/9 of group 3, and 1/10 of group 4 within 6 mo (groups 1 vs 2, P = NS; groups 1 vs 3, P = 0.002; groups 1vs 4, P<0.0001). HBV DNA fell below the detection limit in all 10 patients of group 1, 7/8 of group 2, 0/9 of group 3, and 0/10 of group 4 within 6 mo (groups 1 vs 2, P = NS). HBeAg became seronegative in 7/10 patients of group 1, 1/8 of group 2, 3/9 of group 3, and 0/10 of group 4 within 12 mo (groups 1 vs2, P= 0.02;groups 1 vs 3, P = NS).CONCLUSION: Our data suggest that HBeAg-positive patients with higher ALT levels can be considered good candidates for lamivudine therapy, probably because lamivudine accelerates the natural seroconversion of HBeAg, accompanied by HBV DNA loss, in these patients.
基金supported by the National Basic Research Program of China(2007CB512900)
文摘Naturally occurring mutations in surface proteins of Hepatitis B virus(HBV) usually result in altered hepatitis B surface antigen(HBsAg) secretion efficiency.In the present study,we reported two conserved residues,M75 and M103 with respect to HBsAg,mutations of which not only attenuated HBsAg secretion(M75 only),but also suppressed HBV genome replication without compromising the overlapping p-gene product.We also found M75 and M103 can initiate truncated surface protein(TSPs) synthesis upon over-expression of full-length surface proteins,which may possibly contribute to HBV genome replication.However,attempts to rescue replicationdefective HBV mutant by co-expression of TSPs initiated from M75 or M103 were unsuccessful,which indicated surface proteins rather than the putative TSPs were involved in regulation of HBV genome replication.