The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ...The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.展开更多
BACKGROUND: Phage display technology has become a vital tool in studies aimed at identifying molecules binding to a specific target. It enables the rapid generation and selection of high affinity, fully human antibody...BACKGROUND: Phage display technology has become a vital tool in studies aimed at identifying molecules binding to a specific target. It enables the rapid generation and selection of high affinity, fully human antibody product candidates to essentially any disease target appropriate for antibody therapy. In this study, we prepared the recombinant single-chain fragment variable ( ScFv) antibody to hepatitis B virus surface antigen (HBsAg) by the phage display technology for obtaining a virus-targeting mediator. METHODS: mRNA was isolated from B-lymphocytes from a healthy volunteer and converted into cDNA. The fragment variables of heavy and light chain were amplified separately and assembled into ScFv DNA with a specially constructed DNA linker by polymerase chain reaction. The ScFv DNA was ligated into the phagmid vector pCANT-AB5E and the ligated sample was transformed into competent E. coli TG1. The transformed cells were infected with M13K07 helper phage to form a human recombinant phage antibody library. The volume and recombinant rate of the library were evaluated by bacterial colony count and restriction analysis. After two rounds of panning with HBsAg. the phage clones displaying ScFv of the antibody were selected by enzyme-linked immunosorbant assay ( ELISA) from the enriched phage clones. The antigen binding affinity of the positive clone was detected by competition ELISA. HB2151 E. coli was transfected with the positive phage clone demonstrated by competition ELISA for production of a soluble form of the anti-HBsAg ScFv. ELISA assay was used to detect the antigen binding affinity of the soluble anti-HBsAg ScFv. Finally, the relative molecular mass of soluble anti-HBsAg ScFv was measured by SDS-PAGE. RESULTS: The variable heavy ( VH ) and variable light (VL) and ScFv DNAs were about 340bp, 320bp and 750bp, respectively. The volume of the library was up to 2 × 106 and 8 of 10 random clones were recombinants. Two phage clones could strongly compete with the original HBsAb for binding to HBsAg. Within 2 strong positive phage clones, the soluble anti-HBsAg ScFv from one clone was found to have the binding activity with HBsAg. SDS-PAGE showed that the relative molecular weight of soluble anti-HBsAg ScFv was 32 kDa. CONCLUSION: The anti-HBsAg ScFv successfully produced by phage antibody technology may be useful for broadening the scope of application of the antibody.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)may be caused by hepatitis B virus(HBV)infection.Post-infection recovery-associated changes of HBV indicators include decreased hepatitis B surface antigen(HBsAg)level and incre...BACKGROUND Hepatocellular carcinoma(HCC)may be caused by hepatitis B virus(HBV)infection.Post-infection recovery-associated changes of HBV indicators include decreased hepatitis B surface antigen(HBsAg)level and increased anti-HBsAg antibody titer.Testing to detect HBV DNA is conducted rarely but could detect latent HBV infection persisting after acute infection and prompt administration of treatments to clear HBV and prevent subsequent HBV-induced HCC deve-lopment.Here,we present an HCC case with an extremely high anti-HBsAg antibody titer and latent HBV infection.CASE SUMMARY A 57-year-old male patient with abdominal pain who was diagnosed with primary HCC presented with an extremely high level(over 2000 ng/mL)of serum alpha-fetoprotein.Abdominal B-ultrasonography and computed tomography scan results indicated focal liver lesion and mild splenomegaly.Assessments of serological markers revealed a high titer of antibodies against hepatitis B core antigen(anti-HBcAg antibodies),an extremely high titer(1000 mIU/mL)of hepatitis B surface antibodies(anti-HBsAg antibodies,anti-HBs)and absence of detectible HBsAg.Medical records indicated that the patient had reported no history of HBV vaccination,infection or hepatitis.Therefore,to rule out latent HBV infection in this patient,a serum sample was collected then tested to detect HBV DNA,yielding a positive result.Based on the aforementioned information,the final diagnosis was HCC associated with hepatitis B in a compensated stage of liver dysfunction and the patient was hospitalized for surgical treatment.CONCLUSION A rare HCC case with high serum anti-HBsAg antibody titer and detectable HBV DNA resulted from untreated latent HBV infection.展开更多
AIM:To better understand the clinical significance of hepatitis B seroiogic markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers, the incidence of maternal seroiogic markers of hepatitis B vi...AIM:To better understand the clinical significance of hepatitis B seroiogic markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers, the incidence of maternal seroiogic markers of hepatitis B via placenta and its transformation in these babies were investigated. METHODS: Mothers with positive HBsAg were selected in the third trimester of pregnancy. Their babies received immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine after birth, and were consecutively followed up for hepatitis B seroiogic markers and HBV DNA at birth, mo 1, 4, 7, 12, and 24. RESULTS: Forty-two babies entered the study, including 16 born to hepatitis B e antigen (HBeAg)-positive HBsAg carrier mothers and 26 to HBeAg-negative HBsAg carrier mothers. Apart from four babies born to HBeAg-positive carrier mothers and demonstrated persistent positive HBeAg eventually became HBV carriers, all other babies developed anti-HBs before 12 mo of age. Among the other 12 babies born to HBeAg-positive carrier mothers, HBeAg was detected in 7 at birth, in 4 at mo 1, and in none of them thereafter. No antibody response to the transplacental HBeAg was detected. Among the babies born to HBeAg-negative carrier mothers, anti-HBe was detected 100% at birth and mo 1, in 88.5% at mo 4, in 46.2% at mo 7, in 4.2% at mo 12 and none in mo 24. Among all the immunoprophylaxis-protected babies born to either HBeAg-positive or HBeAg-negative carrier mothers, anti-HBc was detected in 100% at birth, mo 1 and mo 4, in 78.9% at mo 7, in 36.1% at mo 12 and in none at mo 24. CONCLUSION: HBeAg can pass through human placenta from mother to fetus and become undetectable before 4 mo of age, but no antibodies response to the transplacental HBeAg can be detected till mo 24 in the immunoprophylaxis-protected babies. The sole existence of anti-HBe before 1 year of age or anti-HBc before 2 years of age in babies born to HBsAg carrier mothers may simply represent the transplacental maternal antibodies, instead of indicators of HBV infection status.展开更多
AIM: To investigate the clinical significance and presence of mutations in the surface (S) and overlapping polymerase gene of hepatitis B patients with coexisting HBsAg and anti-HBs. METHODS: Twenty-three patients...AIM: To investigate the clinical significance and presence of mutations in the surface (S) and overlapping polymerase gene of hepatitis B patients with coexisting HBsAg and anti-HBs. METHODS: Twenty-three patients with chronic hepatitis B were studied. Of the 23 patients, i i were both positive for hepatitis B virus (HBV) surface antigen (HBsAg) and antibody to HBV surface antigen (anti-HBs), 12 were negative for anti-HBs while positive for HBsAg. DNA was extracted from 200 μL serum of the patients. Nucleotide of the surface and overlapping polymerase gene from HBV-infected patients was amplified by PCR, and the PCR products were sequenced. RESULTS: Forty-one mutations were found within the surface gene protein of HBV in 15 patients (10 with coexisting HBsAg and anti-HBs). Six (14.6%) out of 41 mutations were located at "α" determinant region in 5 patients (4 positive for HBsAg and anti-HBs). Eleven mutations (26.8%) occurred in the downstream or upstream of "α" determinant region. Lamivudine (LMV)- selected mutations were found in three patients who developed anti-HBs, which occurred in amino acid positions (196, 198, 199) of the surface protein and in YMDD motif (M204I/V) of the polymerase protein simultaneously. Presence of these mutations did not relate to changes in ALT and HBV DNA levels.CONCLUSION: Besides mutations in the "α" determinant region, mutations at downstream or upstream of the "α" determinant region may contribute to the development of anti-HBs. These mutations do not block the replicating competency of HBV in the presence of high titer of anti-HBs.展开更多
AIM: To establish a convenient immunoassay method based on recombinant antigen preS1(21-119aa) to detect anti-preS1 antibodies and evaluate the clinical significance of antibodies in hepatitis B. METHODS: The expressi...AIM: To establish a convenient immunoassay method based on recombinant antigen preS1(21-119aa) to detect anti-preS1 antibodies and evaluate the clinical significance of antibodies in hepatitis B. METHODS: The expression plasmid pET-28a-preS1 was constructed, and a large quantity of preS1(21-119aa) fragment of the large HBsAg protein was obtained. The preS1 fragment purified by Ni(2+)-IDA affinity chromatography was used as coated antigen to establish the indirect ELISA based on streptavidin-biotin system for detection of the anti-preS1 antibodies in sera from HBV-infected patients. For follow-up study, serial sera were collected during the clinical course of 21 HBV-infected patients and anti-preS1 antibodies, preS1 antigen, HBV-DNA and other serological HBV markers were analyzed. RESULTS: preS1(21-119aa) fragment was highly expressed from the plasmid pET-28a-preS1 in a soluble form in E.Coli (30mg.L(-1)), and easily purified to high purity over 90% by one step of Ni(2+)-IDA-sepharose 6B affinity chromatography. The purity and antigenicity of the purified preS1(21-119aa) protein was determined by 150g.L(-1) SDS-PAGE, Western blot and a direct ELISA. Recombinant preS1(21-119aa) protein was successfully applied in the immunoassay which could sensitively detect the anti-preS1 antibodies in serum specimens of acute or chronic hepatitis B patients. Results showed that more than half of 19 acute hepatitis B patients produced anti-preS1 antibodies during recovery of the disease, however, the response was only found in a few of chronic patients. In the clinical follow-up study of 11 patients with anti-preS1 positive serological profile, HBsAg and HBV-DNA clearance occurred in 6 of 10 acute hepatitis B patients in 5-6 months, and seroconversion of HBeAg and disappearance of HBV-DNA occurred in 1 chronic patients treated with lavumidine, a antiviral agent. CONCLUSION: The high-purity preS1(21-119aa) coated antigen was successfully prepared by gene expression and affinity chromatography. Using this antigen, a conveniently detective system of anti-preS1 antibodies in sera was established. Preliminarily clinical trial the occurrence of anti-preS1 antibodies in acute hepatitis B patients suggests the clearance of HBV from serum in a short-term time, and anti-preS1 positive in chronic patients means health improvement or recovery from the disease.展开更多
AIM: To assess the prevalence of hepatitis B and C serological markers in a population of refugees living in Athens.METHODS: One hundred and thirty refugees (81 males and 49 females, mean age ±SD: 31.7±8 yea...AIM: To assess the prevalence of hepatitis B and C serological markers in a population of refugees living in Athens.METHODS: One hundred and thirty refugees (81 males and 49 females, mean age ±SD: 31.7±8 years) were included in the study. The hepatitis B virus surface antigen (HBsAg),the hepatitis B virus core antibody (anti-HBc) and the hepatitis C virus antibody (anti-HCV) were detected using a third-generation immunoassay.RESULTS: Twenty individuals (15.4%) were HBsAg positive and 69 (53.1%) were anti-HBc positive. The prevalence of HBsAg and anti-HBc was higher among refugees from Albania and Asia (statistical significant difference, P<0.008 and P<0.001 respectively). The prevalence of these markers was found irrelevant to age or sex. Anti-HCV was detected in the serum of 3 individuals (2.3 %). No differences among age, sex or ethnicity regarding anti-HCV prevalence were found.CONCLUSION: It can be concluded that refugees living in Athens are an immigrant population characterized by a high incidence of HBV infection. The prevalence of HBV markers is higher among refugees from Albania and Asia. It is therefore believed that the adherence to general precautions and the initiation of HBV vaccination programs will be necessary in the future, especially in these communities.Although the prevalence of HCV infection seems to be relatively low, extended epidemiological surveys are needed to provide valid results.展开更多
Our understanding of hepatitis B virus(HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen(HBs Ag)-positive individuals has b...Our understanding of hepatitis B virus(HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen(HBs Ag)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosisfactor(anti-TNF) and hematopoietic stem cell transplantation(HSCT). HBV reactivation could also occur in HBs Ag-negative, antibody to hepatitis B core antigen(anti-HBc) positive individuals during therapies containing rituximab, anti-TNF or HSCT.For HBs Ag-positive patients, prophylactic antiviral therapy is proven to the effective in preventing HBV reactivation. Recent evidence also demonstrated entecavir to be more effective than lamivudine in this aspect. For HBs Ag-negative, antiHBc positive individuals, the risk of reactivations differs with the type of immunosuppression. For rituximab, a prospective study demonstrated the 2-year cumulative risk of reactivation to be 41.5%, but prospective data is still lacking for other immunosupressive regimes. The optimal management in preventing HBV reactivation would involve appropriate risk stratification for different immunosuppressive regimes in both HBs Ag-positive and HBs Ag-negative, anti-HBc positive individuals.展开更多
INTRODUCTIONHepatitis B virus (HBV) belongs to the group ofhepatovirus, a major pathogen of human acute andchronic hepatitis B[1 4], which has a very closeassociation with human hepatocellular carcinoma(HCC)[5-8], For...INTRODUCTIONHepatitis B virus (HBV) belongs to the group ofhepatovirus, a major pathogen of human acute andchronic hepatitis B[1 4], which has a very closeassociation with human hepatocellular carcinoma(HCC)[5-8], For example, a statistical data from ahospital in Shanghai showed that 80% of HCCpatients were positive for HBsAg ( personalcommunication).展开更多
INTRODUCTIONHepatitis B viral infection, one of the most-prevalent liver disorders in China and Korea, is aserious infectious disease as it has the potential ofprogressing into liver cirrhosis and primary hepaticcarci...INTRODUCTIONHepatitis B viral infection, one of the most-prevalent liver disorders in China and Korea, is aserious infectious disease as it has the potential ofprogressing into liver cirrhosis and primary hepaticcarcinoma. China and Korea both belong to high-risk endemic regions of viral hepatitis[1]. TheHBsAg positive rates in China ranged from 6.9% -17.9% by age, race and test methods[2-5].展开更多
liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especial...liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especially hepatitis B surface antigen(HBsAg)loss,necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA(cccDNA).New drugs that target distinct steps of the HBV life cycle have been investigated,which comprise inhibiting the entry of HBV into hepatocytes,disrupting or silencing HBV cccDNA,modulating nucleocapsid assembly,interfering HBV transcription,and inhibiting HBsAg release.The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication.This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs.Hopefully,with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle,the ultimate eradication of CHB infection will soon be achieved.展开更多
A contrast study on the effects of manual acupuncture and electroacupuncture wasconducted in 60 cases of chronic hepatitis B carriers.The results demonstrated that theimmunological functions,both cellular and humoral,...A contrast study on the effects of manual acupuncture and electroacupuncture wasconducted in 60 cases of chronic hepatitis B carriers.The results demonstrated that theimmunological functions,both cellular and humoral,were markedly regulated asevidenced by the negative turnover rates of HBsAg,HBeAg,anti-HBc and HBcAg,as wellas the positive turnover rate of anti-HBe.展开更多
BACKGROUND Reactivation of hepatitis B virus(HBV)during anticancer treatment is a critical issue.When treating patients with solid tumors,it is unclear whether specific cancer types or treatments affect HBV reactivati...BACKGROUND Reactivation of hepatitis B virus(HBV)during anticancer treatment is a critical issue.When treating patients with solid tumors,it is unclear whether specific cancer types or treatments affect HBV reactivation in hepatitis B surface antigen(HBsAg)-negative and hepatitis B core antibody(HBcAb)-positive patients,socalled de novo hepatitis B patients.The risk of de novo hepatitis B may vary based on different background factors.AIM To determine the frequency and risk factors for de novo hepatitis B during solid tumor treatment.METHODS This retrospective cohort study comprised 1040 patients without HBsAgs and with HBcAbs and/or hepatitis B surface antibodies(HBsAbs).The patients were treated for solid cancer from 2008 to 2018 at the National Kyushu Cancer Center and underwent HBV DNA measurements.Patient characteristics and disease and treatment information were investigated.HBV DNA measurements were performed using TaqMan polymerase chain reaction(PCR).To identify the risk factors associated with HBV DNA expression,the age,sex,original disease,pathology,treatment method,presence or absence of hepatitis C virus(HCV),and HBsAb and/or HBcAb titers of all subjects were investigated.In patients with HBV DNA,the time of appearance,presence of HBsAgs and HBsAbs at the time of appearance,and course of the subsequent fluctuations in virus levels were also investigated.RESULTS Among the 1040 patients,938 were HBcAb positive,and 102 were HBcAb negative and HBsAb positive.HBV DNA expression was observed before the onset of treatment in nine patients(0.9%)and after treatment in 35 patients(3.7%),all of whom were HBcAb positive.The HBV reactivation group showed significantly higher median HBcAb values[9.00(8.12-9.89)vs 7.22(7.02-7.43),P=0.0001]and significantly lower HBsAb values(14 vs 46,P=0.0342)than the group without reactivation.Notably,the reactivated group showed a significantly higher proportion of cancers in organs related to digestion and absorption(79.0%vs 58.7%,P=0.0051).A high HBcAb titer and cancers in organs involved in digestion and absorption were identified as independent factors for HBV reactivation(multivariate analysis,P=0.0002 and P=0.0095).The group without HBsAbs tended to have a shorter time to reactivation(day 43 vs day 193),and the frequency of reactivation within 6 mo was significantly higher in this group(P=0.0459)than in the other group.CONCLUSION A high HBcAb titer and cancers in organs involved in digestion and absorption are independent factors that contribute to HBV reactivation during solid tumor treatment.展开更多
<strong>Introduction:</strong> The endemic nature of hepatitis B virus (HBV) in Sub-Saharan Africa is a significant public health problem that places health care providers (medical students inclusive) at i...<strong>Introduction:</strong> The endemic nature of hepatitis B virus (HBV) in Sub-Saharan Africa is a significant public health problem that places health care providers (medical students inclusive) at increased risk of occupational exposure. However, vaccination against HBV is not systematic among medical students in Cameroon. Thus, we sought to evaluate awareness and HBV vaccine coverage amongst medical students in Cameroon. <strong>Aim:</strong> The present study was aimed at determining the proportion of Medical and Paramedical students on internship at the Bamenda Regional Hospital (BRH) who are vaccinated and immune to hepatitis B virus (HBV). <strong>Methods:</strong> This was a hospital-based cross sectional study carried out at the BRH in Cameroon. Questionnaires were administered to 120 participants who signed an informed consent form and venous blood samples collected in dry tubes for the HBV-5 PANEL test. Data were collected within a period of two weeks. HBV vaccine status was defined as complete (3 doses), partial (1 or 2 doses), and unvaccinated. <strong>Results:</strong> Of 120 participants (87 females and 33 males), 56 (46.7%) were vaccinated at least once against HBV;15 (12.5%) were partially vaccinated and 41 (34.2%) completely vaccinated. Out of the 56 vaccinated individuals, only 13 (23.2%) were confirmed immunized against HBV by testing positive for hepatitis B surface antibodies. Only 3 (5.4%) students had done post-vaccination serologic test to confirm their immunized status. There was high exposure to potentially infected body fluids like blood (97.5%) and urine (87.5%). There was equally poor practice of adequate preventive measures like regular hand washing and the proper use of personal protective equipment. A prevalence of 3.1% of HBV amongst the unvaccinated group was recorded. <strong>Conclusion:</strong> Only 1 in 3 medical students had completed the HBV vaccination series and only 26.8% of this cohort was confirmed immunized against HBV. This highlights the need for improved health policies aimed at increasing access and coverage of HBV immunization in high risk groups such as health workers.展开更多
Viral hepatitis is a global threat to public health and one of the leading causes of death worldwide.Often,acute viral cases in children and adults are associated with viral hepatitis A,B,C,D and E,or co-infection wit...Viral hepatitis is a global threat to public health and one of the leading causes of death worldwide.Often,acute viral cases in children and adults are associated with viral hepatitis A,B,C,D and E,or co-infection with two types of hepatitis.Infection with these viruses is a global health problem and continuous efforts are in place to identify infected people through targeted screening,preventing new infections through vaccination,monitoring and treating people at risk for complications of all types of hepatitis.The aim of this study was to determine the evaluate the prevalence and trends of hepatitis B and C infection in the Nahavand city during 5 consecutive years(2013–2017).The total number of patients with hepatitis B and C was 141 persons from March 2013 to March 2017,of these,101 had hepatitis B,and 40 had hepatitis C.The prevalence of hepatitis B and C was higher in men than women.The percentage frequency hepatitis B in the city in the last five years was 0.05 percent.11 cases(10.89%)pregnant women and Six cases(5.9%)receiving blood(blood transfusions)in Hepatitis B was observed.the prevalence of hepatitis C was 0.2%at the end of 2017.The study on the cause of hepatitis C in Nahavand has shown that 21(52.5%)of the total of 40 people were infected with addiction.The interesting point in this report is that according to reports from viral hepatitis testing questionnaires,24 of 101 people with type B hepatitis have 23.7%of people with a history of complete vaccination of hepatitis B and one person(0.9%)had incomplete vaccination.A significant relationship was found between the level of education and the prevalence of hepatitis(P=0.005).展开更多
文摘The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.
基金This study was supported by grants from the National Natural Science Foundation of China (No. 30572213)and Student Innovation Program of Shanxi Medical University (No.200404).
文摘BACKGROUND: Phage display technology has become a vital tool in studies aimed at identifying molecules binding to a specific target. It enables the rapid generation and selection of high affinity, fully human antibody product candidates to essentially any disease target appropriate for antibody therapy. In this study, we prepared the recombinant single-chain fragment variable ( ScFv) antibody to hepatitis B virus surface antigen (HBsAg) by the phage display technology for obtaining a virus-targeting mediator. METHODS: mRNA was isolated from B-lymphocytes from a healthy volunteer and converted into cDNA. The fragment variables of heavy and light chain were amplified separately and assembled into ScFv DNA with a specially constructed DNA linker by polymerase chain reaction. The ScFv DNA was ligated into the phagmid vector pCANT-AB5E and the ligated sample was transformed into competent E. coli TG1. The transformed cells were infected with M13K07 helper phage to form a human recombinant phage antibody library. The volume and recombinant rate of the library were evaluated by bacterial colony count and restriction analysis. After two rounds of panning with HBsAg. the phage clones displaying ScFv of the antibody were selected by enzyme-linked immunosorbant assay ( ELISA) from the enriched phage clones. The antigen binding affinity of the positive clone was detected by competition ELISA. HB2151 E. coli was transfected with the positive phage clone demonstrated by competition ELISA for production of a soluble form of the anti-HBsAg ScFv. ELISA assay was used to detect the antigen binding affinity of the soluble anti-HBsAg ScFv. Finally, the relative molecular mass of soluble anti-HBsAg ScFv was measured by SDS-PAGE. RESULTS: The variable heavy ( VH ) and variable light (VL) and ScFv DNAs were about 340bp, 320bp and 750bp, respectively. The volume of the library was up to 2 × 106 and 8 of 10 random clones were recombinants. Two phage clones could strongly compete with the original HBsAb for binding to HBsAg. Within 2 strong positive phage clones, the soluble anti-HBsAg ScFv from one clone was found to have the binding activity with HBsAg. SDS-PAGE showed that the relative molecular weight of soluble anti-HBsAg ScFv was 32 kDa. CONCLUSION: The anti-HBsAg ScFv successfully produced by phage antibody technology may be useful for broadening the scope of application of the antibody.
文摘BACKGROUND Hepatocellular carcinoma(HCC)may be caused by hepatitis B virus(HBV)infection.Post-infection recovery-associated changes of HBV indicators include decreased hepatitis B surface antigen(HBsAg)level and increased anti-HBsAg antibody titer.Testing to detect HBV DNA is conducted rarely but could detect latent HBV infection persisting after acute infection and prompt administration of treatments to clear HBV and prevent subsequent HBV-induced HCC deve-lopment.Here,we present an HCC case with an extremely high anti-HBsAg antibody titer and latent HBV infection.CASE SUMMARY A 57-year-old male patient with abdominal pain who was diagnosed with primary HCC presented with an extremely high level(over 2000 ng/mL)of serum alpha-fetoprotein.Abdominal B-ultrasonography and computed tomography scan results indicated focal liver lesion and mild splenomegaly.Assessments of serological markers revealed a high titer of antibodies against hepatitis B core antigen(anti-HBcAg antibodies),an extremely high titer(1000 mIU/mL)of hepatitis B surface antibodies(anti-HBsAg antibodies,anti-HBs)and absence of detectible HBsAg.Medical records indicated that the patient had reported no history of HBV vaccination,infection or hepatitis.Therefore,to rule out latent HBV infection in this patient,a serum sample was collected then tested to detect HBV DNA,yielding a positive result.Based on the aforementioned information,the final diagnosis was HCC associated with hepatitis B in a compensated stage of liver dysfunction and the patient was hospitalized for surgical treatment.CONCLUSION A rare HCC case with high serum anti-HBsAg antibody titer and detectable HBV DNA resulted from untreated latent HBV infection.
基金Supported by the Key-Subject Construction Project of Ministry of Public Health of China,No.97030223the young researcher grant from Children's Hospital of Fudan University,No.QN2001-5 Co-first-authors: Jian-She Wang and Hui Chen
文摘AIM:To better understand the clinical significance of hepatitis B seroiogic markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers, the incidence of maternal seroiogic markers of hepatitis B via placenta and its transformation in these babies were investigated. METHODS: Mothers with positive HBsAg were selected in the third trimester of pregnancy. Their babies received immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine after birth, and were consecutively followed up for hepatitis B seroiogic markers and HBV DNA at birth, mo 1, 4, 7, 12, and 24. RESULTS: Forty-two babies entered the study, including 16 born to hepatitis B e antigen (HBeAg)-positive HBsAg carrier mothers and 26 to HBeAg-negative HBsAg carrier mothers. Apart from four babies born to HBeAg-positive carrier mothers and demonstrated persistent positive HBeAg eventually became HBV carriers, all other babies developed anti-HBs before 12 mo of age. Among the other 12 babies born to HBeAg-positive carrier mothers, HBeAg was detected in 7 at birth, in 4 at mo 1, and in none of them thereafter. No antibody response to the transplacental HBeAg was detected. Among the babies born to HBeAg-negative carrier mothers, anti-HBe was detected 100% at birth and mo 1, in 88.5% at mo 4, in 46.2% at mo 7, in 4.2% at mo 12 and none in mo 24. Among all the immunoprophylaxis-protected babies born to either HBeAg-positive or HBeAg-negative carrier mothers, anti-HBc was detected in 100% at birth, mo 1 and mo 4, in 78.9% at mo 7, in 36.1% at mo 12 and in none at mo 24. CONCLUSION: HBeAg can pass through human placenta from mother to fetus and become undetectable before 4 mo of age, but no antibodies response to the transplacental HBeAg can be detected till mo 24 in the immunoprophylaxis-protected babies. The sole existence of anti-HBe before 1 year of age or anti-HBc before 2 years of age in babies born to HBsAg carrier mothers may simply represent the transplacental maternal antibodies, instead of indicators of HBV infection status.
基金Supported by the National Natural Science Foundation of China,No.30271182
文摘AIM: To investigate the clinical significance and presence of mutations in the surface (S) and overlapping polymerase gene of hepatitis B patients with coexisting HBsAg and anti-HBs. METHODS: Twenty-three patients with chronic hepatitis B were studied. Of the 23 patients, i i were both positive for hepatitis B virus (HBV) surface antigen (HBsAg) and antibody to HBV surface antigen (anti-HBs), 12 were negative for anti-HBs while positive for HBsAg. DNA was extracted from 200 μL serum of the patients. Nucleotide of the surface and overlapping polymerase gene from HBV-infected patients was amplified by PCR, and the PCR products were sequenced. RESULTS: Forty-one mutations were found within the surface gene protein of HBV in 15 patients (10 with coexisting HBsAg and anti-HBs). Six (14.6%) out of 41 mutations were located at "α" determinant region in 5 patients (4 positive for HBsAg and anti-HBs). Eleven mutations (26.8%) occurred in the downstream or upstream of "α" determinant region. Lamivudine (LMV)- selected mutations were found in three patients who developed anti-HBs, which occurred in amino acid positions (196, 198, 199) of the surface protein and in YMDD motif (M204I/V) of the polymerase protein simultaneously. Presence of these mutations did not relate to changes in ALT and HBV DNA levels.CONCLUSION: Besides mutations in the "α" determinant region, mutations at downstream or upstream of the "α" determinant region may contribute to the development of anti-HBs. These mutations do not block the replicating competency of HBV in the presence of high titer of anti-HBs.
基金the grants No.KY951-Al-301 and No.KY95T-06-03 from the 9th Five Years Plan Key Research Programs of the Chinese Academy of Sciences.
文摘AIM: To establish a convenient immunoassay method based on recombinant antigen preS1(21-119aa) to detect anti-preS1 antibodies and evaluate the clinical significance of antibodies in hepatitis B. METHODS: The expression plasmid pET-28a-preS1 was constructed, and a large quantity of preS1(21-119aa) fragment of the large HBsAg protein was obtained. The preS1 fragment purified by Ni(2+)-IDA affinity chromatography was used as coated antigen to establish the indirect ELISA based on streptavidin-biotin system for detection of the anti-preS1 antibodies in sera from HBV-infected patients. For follow-up study, serial sera were collected during the clinical course of 21 HBV-infected patients and anti-preS1 antibodies, preS1 antigen, HBV-DNA and other serological HBV markers were analyzed. RESULTS: preS1(21-119aa) fragment was highly expressed from the plasmid pET-28a-preS1 in a soluble form in E.Coli (30mg.L(-1)), and easily purified to high purity over 90% by one step of Ni(2+)-IDA-sepharose 6B affinity chromatography. The purity and antigenicity of the purified preS1(21-119aa) protein was determined by 150g.L(-1) SDS-PAGE, Western blot and a direct ELISA. Recombinant preS1(21-119aa) protein was successfully applied in the immunoassay which could sensitively detect the anti-preS1 antibodies in serum specimens of acute or chronic hepatitis B patients. Results showed that more than half of 19 acute hepatitis B patients produced anti-preS1 antibodies during recovery of the disease, however, the response was only found in a few of chronic patients. In the clinical follow-up study of 11 patients with anti-preS1 positive serological profile, HBsAg and HBV-DNA clearance occurred in 6 of 10 acute hepatitis B patients in 5-6 months, and seroconversion of HBeAg and disappearance of HBV-DNA occurred in 1 chronic patients treated with lavumidine, a antiviral agent. CONCLUSION: The high-purity preS1(21-119aa) coated antigen was successfully prepared by gene expression and affinity chromatography. Using this antigen, a conveniently detective system of anti-preS1 antibodies in sera was established. Preliminarily clinical trial the occurrence of anti-preS1 antibodies in acute hepatitis B patients suggests the clearance of HBV from serum in a short-term time, and anti-preS1 positive in chronic patients means health improvement or recovery from the disease.
文摘AIM: To assess the prevalence of hepatitis B and C serological markers in a population of refugees living in Athens.METHODS: One hundred and thirty refugees (81 males and 49 females, mean age ±SD: 31.7±8 years) were included in the study. The hepatitis B virus surface antigen (HBsAg),the hepatitis B virus core antibody (anti-HBc) and the hepatitis C virus antibody (anti-HCV) were detected using a third-generation immunoassay.RESULTS: Twenty individuals (15.4%) were HBsAg positive and 69 (53.1%) were anti-HBc positive. The prevalence of HBsAg and anti-HBc was higher among refugees from Albania and Asia (statistical significant difference, P<0.008 and P<0.001 respectively). The prevalence of these markers was found irrelevant to age or sex. Anti-HCV was detected in the serum of 3 individuals (2.3 %). No differences among age, sex or ethnicity regarding anti-HCV prevalence were found.CONCLUSION: It can be concluded that refugees living in Athens are an immigrant population characterized by a high incidence of HBV infection. The prevalence of HBV markers is higher among refugees from Albania and Asia. It is therefore believed that the adherence to general precautions and the initiation of HBV vaccination programs will be necessary in the future, especially in these communities.Although the prevalence of HCV infection seems to be relatively low, extended epidemiological surveys are needed to provide valid results.
文摘Our understanding of hepatitis B virus(HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen(HBs Ag)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosisfactor(anti-TNF) and hematopoietic stem cell transplantation(HSCT). HBV reactivation could also occur in HBs Ag-negative, antibody to hepatitis B core antigen(anti-HBc) positive individuals during therapies containing rituximab, anti-TNF or HSCT.For HBs Ag-positive patients, prophylactic antiviral therapy is proven to the effective in preventing HBV reactivation. Recent evidence also demonstrated entecavir to be more effective than lamivudine in this aspect. For HBs Ag-negative, antiHBc positive individuals, the risk of reactivations differs with the type of immunosuppression. For rituximab, a prospective study demonstrated the 2-year cumulative risk of reactivation to be 41.5%, but prospective data is still lacking for other immunosupressive regimes. The optimal management in preventing HBV reactivation would involve appropriate risk stratification for different immunosuppressive regimes in both HBs Ag-positive and HBs Ag-negative, anti-HBc positive individuals.
基金This work was supported by Projects of Tackling Key Problems in ScienceTechnology from the State Science+2 种基金Technology Ministry (TJ99-LA01) Shanghai ScienceTechnology Commission (994919033 )
文摘INTRODUCTIONHepatitis B virus (HBV) belongs to the group ofhepatovirus, a major pathogen of human acute andchronic hepatitis B[1 4], which has a very closeassociation with human hepatocellular carcinoma(HCC)[5-8], For example, a statistical data from ahospital in Shanghai showed that 80% of HCCpatients were positive for HBsAg ( personalcommunication).
基金Project supported by the National Natural Science Foundation of China, No. 39560074Korea ScienceEngineering Foundation, 965-0700-001-2.
文摘INTRODUCTIONHepatitis B viral infection, one of the most-prevalent liver disorders in China and Korea, is aserious infectious disease as it has the potential ofprogressing into liver cirrhosis and primary hepaticcarcinoma. China and Korea both belong to high-risk endemic regions of viral hepatitis[1]. TheHBsAg positive rates in China ranged from 6.9% -17.9% by age, race and test methods[2-5].
文摘liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especially hepatitis B surface antigen(HBsAg)loss,necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA(cccDNA).New drugs that target distinct steps of the HBV life cycle have been investigated,which comprise inhibiting the entry of HBV into hepatocytes,disrupting or silencing HBV cccDNA,modulating nucleocapsid assembly,interfering HBV transcription,and inhibiting HBsAg release.The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication.This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs.Hopefully,with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle,the ultimate eradication of CHB infection will soon be achieved.
文摘A contrast study on the effects of manual acupuncture and electroacupuncture wasconducted in 60 cases of chronic hepatitis B carriers.The results demonstrated that theimmunological functions,both cellular and humoral,were markedly regulated asevidenced by the negative turnover rates of HBsAg,HBeAg,anti-HBc and HBcAg,as wellas the positive turnover rate of anti-HBe.
基金Supported by Eisai Corporation,No.HHCS20181030011。
文摘BACKGROUND Reactivation of hepatitis B virus(HBV)during anticancer treatment is a critical issue.When treating patients with solid tumors,it is unclear whether specific cancer types or treatments affect HBV reactivation in hepatitis B surface antigen(HBsAg)-negative and hepatitis B core antibody(HBcAb)-positive patients,socalled de novo hepatitis B patients.The risk of de novo hepatitis B may vary based on different background factors.AIM To determine the frequency and risk factors for de novo hepatitis B during solid tumor treatment.METHODS This retrospective cohort study comprised 1040 patients without HBsAgs and with HBcAbs and/or hepatitis B surface antibodies(HBsAbs).The patients were treated for solid cancer from 2008 to 2018 at the National Kyushu Cancer Center and underwent HBV DNA measurements.Patient characteristics and disease and treatment information were investigated.HBV DNA measurements were performed using TaqMan polymerase chain reaction(PCR).To identify the risk factors associated with HBV DNA expression,the age,sex,original disease,pathology,treatment method,presence or absence of hepatitis C virus(HCV),and HBsAb and/or HBcAb titers of all subjects were investigated.In patients with HBV DNA,the time of appearance,presence of HBsAgs and HBsAbs at the time of appearance,and course of the subsequent fluctuations in virus levels were also investigated.RESULTS Among the 1040 patients,938 were HBcAb positive,and 102 were HBcAb negative and HBsAb positive.HBV DNA expression was observed before the onset of treatment in nine patients(0.9%)and after treatment in 35 patients(3.7%),all of whom were HBcAb positive.The HBV reactivation group showed significantly higher median HBcAb values[9.00(8.12-9.89)vs 7.22(7.02-7.43),P=0.0001]and significantly lower HBsAb values(14 vs 46,P=0.0342)than the group without reactivation.Notably,the reactivated group showed a significantly higher proportion of cancers in organs related to digestion and absorption(79.0%vs 58.7%,P=0.0051).A high HBcAb titer and cancers in organs involved in digestion and absorption were identified as independent factors for HBV reactivation(multivariate analysis,P=0.0002 and P=0.0095).The group without HBsAbs tended to have a shorter time to reactivation(day 43 vs day 193),and the frequency of reactivation within 6 mo was significantly higher in this group(P=0.0459)than in the other group.CONCLUSION A high HBcAb titer and cancers in organs involved in digestion and absorption are independent factors that contribute to HBV reactivation during solid tumor treatment.
文摘<strong>Introduction:</strong> The endemic nature of hepatitis B virus (HBV) in Sub-Saharan Africa is a significant public health problem that places health care providers (medical students inclusive) at increased risk of occupational exposure. However, vaccination against HBV is not systematic among medical students in Cameroon. Thus, we sought to evaluate awareness and HBV vaccine coverage amongst medical students in Cameroon. <strong>Aim:</strong> The present study was aimed at determining the proportion of Medical and Paramedical students on internship at the Bamenda Regional Hospital (BRH) who are vaccinated and immune to hepatitis B virus (HBV). <strong>Methods:</strong> This was a hospital-based cross sectional study carried out at the BRH in Cameroon. Questionnaires were administered to 120 participants who signed an informed consent form and venous blood samples collected in dry tubes for the HBV-5 PANEL test. Data were collected within a period of two weeks. HBV vaccine status was defined as complete (3 doses), partial (1 or 2 doses), and unvaccinated. <strong>Results:</strong> Of 120 participants (87 females and 33 males), 56 (46.7%) were vaccinated at least once against HBV;15 (12.5%) were partially vaccinated and 41 (34.2%) completely vaccinated. Out of the 56 vaccinated individuals, only 13 (23.2%) were confirmed immunized against HBV by testing positive for hepatitis B surface antibodies. Only 3 (5.4%) students had done post-vaccination serologic test to confirm their immunized status. There was high exposure to potentially infected body fluids like blood (97.5%) and urine (87.5%). There was equally poor practice of adequate preventive measures like regular hand washing and the proper use of personal protective equipment. A prevalence of 3.1% of HBV amongst the unvaccinated group was recorded. <strong>Conclusion:</strong> Only 1 in 3 medical students had completed the HBV vaccination series and only 26.8% of this cohort was confirmed immunized against HBV. This highlights the need for improved health policies aimed at increasing access and coverage of HBV immunization in high risk groups such as health workers.
文摘Viral hepatitis is a global threat to public health and one of the leading causes of death worldwide.Often,acute viral cases in children and adults are associated with viral hepatitis A,B,C,D and E,or co-infection with two types of hepatitis.Infection with these viruses is a global health problem and continuous efforts are in place to identify infected people through targeted screening,preventing new infections through vaccination,monitoring and treating people at risk for complications of all types of hepatitis.The aim of this study was to determine the evaluate the prevalence and trends of hepatitis B and C infection in the Nahavand city during 5 consecutive years(2013–2017).The total number of patients with hepatitis B and C was 141 persons from March 2013 to March 2017,of these,101 had hepatitis B,and 40 had hepatitis C.The prevalence of hepatitis B and C was higher in men than women.The percentage frequency hepatitis B in the city in the last five years was 0.05 percent.11 cases(10.89%)pregnant women and Six cases(5.9%)receiving blood(blood transfusions)in Hepatitis B was observed.the prevalence of hepatitis C was 0.2%at the end of 2017.The study on the cause of hepatitis C in Nahavand has shown that 21(52.5%)of the total of 40 people were infected with addiction.The interesting point in this report is that according to reports from viral hepatitis testing questionnaires,24 of 101 people with type B hepatitis have 23.7%of people with a history of complete vaccination of hepatitis B and one person(0.9%)had incomplete vaccination.A significant relationship was found between the level of education and the prevalence of hepatitis(P=0.005).