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Recurrence and influencing factors of hepatitis B surface antigen seroclearance induced by peginterferon alpha-based regimens
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作者 Rui Lu Meng Zhang +13 位作者 Zi-Han Liu Miao Hao Yan Tian Mei Li Feng-Ping Wu Wen-Jun Wang Juan-Juan Shi Xin Zhang Xiao-Li Jia Zi-Cheng Jiang Xue-Mei Li Guang-Hua Xu Ya-Ping Li Shuang-Suo Dang 《World Journal of Gastroenterology》 SCIE CAS 2024年第44期4725-4737,共13页
BACKGROUND The long-term stability of hepatitis B surface antigen(HBsAg)seroclearance following peginterferon alpha(peg-IFN-α)-based therapy has not been extensively studied,leaving the full potential and limitations... BACKGROUND The long-term stability of hepatitis B surface antigen(HBsAg)seroclearance following peginterferon alpha(peg-IFN-α)-based therapy has not been extensively studied,leaving the full potential and limitations of this strategy unclear.AIM To assess HBsAg recurrence after seroclearance achieved by peg-IFN-αregimens.METHODS This prospective,multicenter,observational study was conducted from November 2015 to June 2021 at three Chinese hospitals:The Second Affiliated Hospital of Xi’an Jiaotong University,Ankang Central Hospital,and The Affiliated Hospital of Yan’an University.Participants who achieved HBsAg seroclearance following peg-IFN-α-based treatments were monitored every 4-12 weeks post-treatment for hepatitis B virus(HBV)markers,HBV DNA,and liver function.The primary outcome was HBV recurrence,defined as the reemergence of HBsAg,HBV DNA,or both,at least twice within 4-8 weeks of follow-up.RESULTS In total,121 patients who achieved HBsAg seroclearance were enrolled.After a median follow-up of 84.0(48.0,132.0)weeks,four subjects were lost to follow-up.HBsAg recurrence was detected in 16 patients.The cumulative HBsAg recurrence rate in the intention-to-treat population was 15.2%.Multivariate logistic regression analysis demonstrated that consolidation time<12 weeks[odds ratio(OR)=28.044,95%CI:4.525-173.791]and hepatitis B surface antibody disappearance during follow-up(OR=46.445,95%CI:2.571-838.957)were strong predictors of HBsAg recurrence.HBV DNA positivity and decompensation of liver cirrhosis and hepatocellular carcinoma were not observed.CONCLUSION HBsAg seroclearance following peg-IFN-αtreatment was durable over 84 weeks of follow-up with a cumulative recurrence rate of 15.2%. 展开更多
关键词 Chronic hepatitis b Peginterferon alpha hepatitis b surface antigen seroclearance hepatitis b surface antigen recurrence Clinical cure
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Hepatitis B surface antigen-negative but hepatitis B envelope antigen-positive false occult hepatitis B virus infection:A case report
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作者 Shu-Sheng Yang Fei Fu +4 位作者 Qian-Kun Xuan Zhou-Xiang Zhang Zhi-Jun Li Guang-Bo Li Xiao-Yu Yu 《World Journal of Hepatology》 2024年第10期1199-1207,共9页
BACKGROUND Occult hepatitis B infection(OBI)is characterized by the detection of hepatitis B virus(HBV)DNA in serum(usually HBV DNA<200 IU/mL)or the liver but negativity for hepatitis B surface antigen(HBsAg).The d... BACKGROUND Occult hepatitis B infection(OBI)is characterized by the detection of hepatitis B virus(HBV)DNA in serum(usually HBV DNA<200 IU/mL)or the liver but negativity for hepatitis B surface antigen(HBsAg).The diagnosis of OBI relies on the sensitivity of assays used in the detection of HBV DNA and HBsAg.HBsAg assays with inadequate sensitivity or inability to detect HBV S variants may lead to misdiagnosis of OBI in people with overt HBV infection.CASE SUMMARY We report a HBsAg-negative but hepatitis B envelope antigen-positive patient who had a significant HBV DNA level.The patient was initially diagnosed as having OBI.However,sequence analysis revealed a unique insertion of amino acid residues at positions 120-124 in the S protein,which affects the formation of a disulfide bond that is associated with the formation of a loop.It is well known that there is an overlap between the S protein and Pol protein.We found that this new insertion site occurred in polymerase/reverse transcriptase domain,indi-cating that this insertion might be involved in HBV pathogenicity.The patient was finally diagnosed with a false OBI.CONCLUSION An insertion of amino acid residues at positions 120-124 of the S protein affects the formation of immunodominant epitopes and results in negative HBsAg levels. 展开更多
关键词 Occult hepatitis b infection hepatitis b virus hepatitis b surface antigen hepatitis b envelope antigen Immunodominant epitopes Case report
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Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen:Novel viral biomarkers for chronic hepatitis B management
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作者 Wattana Leowattana Pathomthep Leowattana Tawithep Leowattana 《World Journal of Hepatology》 2024年第4期550-565,共16页
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
关键词 Quantitative hepatitis b core antibody Quantitative hepatitis b surface antigen Chronic hepatitis b management Novels viral biomarkers
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The Relationship between Intrahepatic Distribution of Hepatitis B Virus Core Antigen and Serum ALT, HBV DNA Levels and HBeAg Status 被引量:4
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作者 Qing He Qi-yuan Tang +7 位作者 Xiao-hua Le De-liang Lv Xiang-mei Zhang Fei-jian Ao Yi-min Tang Shan Huang John Nunnari Gui-lin Yang 《国际感染病学(电子版)》 CAS 2012年第2期84-90,共7页
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
关键词 HbcAg distribution IMMUNOHISTOCHEMISTRY HbV DNA Chronic hepatitis b hbeag ALT
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Prevention of hepatitis B reactivation in patients with hematologic malignancies treated with novel systemic therapies:Who and Why?
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作者 Matteo Tonnini Clara Solera Horna Luca Ielasi 《World Journal of Gastroenterology》 SCIE CAS 2024年第5期509-511,共3页
The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis w... The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy. 展开更多
关键词 hepatitis b reactivation hepatitis b virus Antiviral prophylaxis Hematologic malignancies Chimeric antigens receptor-T cell therapy Immune checkpoint inhibitors
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Immunoprophylaxis failure and vaccine response in infants born to mothers with chronic hepatitis B infection in Djibouti
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作者 Sahal Darar Dirir Ambroise D Ahouidi +6 位作者 Aboubacry Drame Warsama Osman Abdi Guelleh Youssouf Kayad Mohamed Houmed Aboubakar Makhtar Camara Coumba Toure Kane Halimatou Diop Ndiaye 《World Journal of Hepatology》 2024年第7期1039-1050,共12页
BACKGROUND In endemic areas,vertical transmission of hepatitis B virus(HBV)remains a major source of the global reservoir of infected people.Eliminating mother-to-child transmission(MTCT)of HBV is at the heart of Worl... BACKGROUND In endemic areas,vertical transmission of hepatitis B virus(HBV)remains a major source of the global reservoir of infected people.Eliminating mother-to-child transmission(MTCT)of HBV is at the heart of World Health Organization’s goal of reducing the incidence of HBV in children to less than 0.1%by 2030.Universal screening for hepatitis B during pregnancy and neonatal vaccination are the main preventive measures.AIM To evaluate the efficacy of HBV vaccination combined with one dose of immunoglobulin in children born to hepatitis B surface antigen(HBsAg)-positive mothers in Djibouti city.METHODS We conducted a study in a prospective cohort of HBsAg-positive pregnant women and their infants.The study ran from January 2021 to May 2022,and infants were followed up to 7 mo of age.HBV serological markers and viral load in pregnant women were measured using aVidas microparticle enzyme-linked immunosorbent assay(Biomérieux,Paris,France)and the automated Amplix platform(Biosynex,Strasbourg,France).All infants received hepatitis B immunoglobulin and were vaccinated against HBV at birth.These infants were closely monitored to assess their seroprotective response and for failure of immunoprophylaxis.Simple logistic regression was also used to identify risk factors associated with immunoprophylaxis failure and poor vaccine response.All statistical analyses were performed with version 4.0.1 of the R software.RESULTS Of the 50 pregnant women recruited,the median age was 31 years,ranging from 18 years to 41 years.The MTCT rate in this cohort was 4%(2/50)in HBsAg-positive women and 67%(2/3)in hepatitis B e antigen-positive women with a viral load>200000 IU/mL.Of the 48 infants who did not fail immunoprophylaxis,8(16%)became poor responders(anti-HB<100 mIU/mL)after HBV vaccination and hepatitis B immunoglobulin,while 40(84%)infants achieved a good level of seroprotection(anti-HB>100 mIU/mL).Factors associated with this failure of immunoprophylaxis were maternal HBV DNA levels(>200000 IU/mL)and hepatitis B e antigen-positive status(odds ratio=158,95%confidence interval:5.05-4958,P<0.01).Birth weight<2500 g was associated with a poor immune response to vaccination(odds ratio=34,95%confidence interval:3.01-383.86,P<0.01).CONCLUSION Despite a failure rate of immunoprophylaxis higher than the World Health Organization target,this study showed that the combination of immunoglobulin and HBV vaccine was effective in preventing MTCT of HBV.Therefore,further studies are needed to better understand the challenges associated with immunoprophylaxis failure in infants in Djibouti city. 展开更多
关键词 hepatitis b surface antigen INFANTS hepatitis b immunoglobulin hepatitis vaccine DJIbOUTI
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Preliminary results of Thymosin-a1 versus interferon-α treatment in patients with HBeAg negative and serum HBV DNA positive chronic hepatitis B 被引量:23
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作者 Lin Zhuang Jing You Bao Zhang Tang Su Ying Ding Kui Hua Yan Dan Peng Yan Mei Zhang Lu Zhang ~1Department of Hepatology,Kunming Third Municipal Peoples Hospital,Kunming 650041,Yunnan Province,China ~2Department of Infectious Diseases,The First Affiliated Hospital of Kunming Medical College,Kunming 650032,Yunnan Province,China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第3期407-410,共4页
INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 a... INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer . 展开更多
关键词 hepatitis b hepatitis b surface antigens INTERFERON-Α thymosin-a1 hepatitis b E antigens SEROLOGY
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Serum hepatitis B virus RNA is a predictor of HBeAg seroconversion and virological response with entecavir treatment in chronic hepatitis B patients 被引量:18
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作者 Hao Luo Xia-Xia Zhang +5 位作者 Li-Hua Cao Ning Tan Qian Kang Hong-Li Xi Min Yu Xiao-Yuan Xu 《World Journal of Gastroenterology》 SCIE CAS 2019年第6期719-728,共10页
BACKGROUND Characteristics of alterations of serum hepatitis B virus(HBV) RNA in different chronic hepatitis B(CHB) patients still cannot be fully explained. Whether HBV RNA can predict HBeAg seroconversion is still c... BACKGROUND Characteristics of alterations of serum hepatitis B virus(HBV) RNA in different chronic hepatitis B(CHB) patients still cannot be fully explained. Whether HBV RNA can predict HBeAg seroconversion is still controversial.AIM To investigate whether HBV RNA can predict virological response or HBeAg seroconversion during entecavir(ETV) treatment when HBV DNA is undetectable.METHODS The present study evaluated 61 individuals who were diagnosed and treated with long-term ETV monotherapy at the Department of Infectious Diseases of Peking University First Hospital(China) from September 2006 to December 2007.Finally, 30 treatment-naive individuals were included. Serum HBV RNA were extracted from 140 μL serum samples at two time points. Then they were reverse transcribed to cDNA with the HBV-specific primer. The product was quantified by real-time quantitative PCR(RT-PCR) using TAMARA probes. Statistical analyses were performed with IBM SPSS 20.0.RESULTS Level of serum HBV RNA at baseline was 4.15 ± 0.90 log10 copies/mL. HBV RNA levels showed no significant difference between the virological response(VR)and partial VR(PVR) groups at baseline(P = 0.940). Serum HBV RNA significantly decreased among patients who achieved a VR during ETV therapy(P < 0.001). The levels of HBV RNA in both HBeAg-positive patients with seroconversion group and those with no seroconversion increased after 24 wk of treatment. Overall, HBV RNA significantly but mildly correlated to HBsAg(r =0.265, P = 0.041), and HBV RNA was not correlated to HBV DNA(r = 0.242, P =0.062). Furthermore, serum HBV RNA was an independent indicator for predicting HBeAg seroconversion and virological response. HBeAg seroconversion was more likely in CHB patients with HBV RNA levels below4.12 log10 copies/mL before treatment.CONLUSION The level of serum HBV RNA could predict HBeAg seroconversion and PVR during treatment. In the PVR group, the level of serum HBV RNA tends to be increasing. 展开更多
关键词 Chronic hepatitis b hepatitis b virus RNA Virological response hbeag SEROCONVERSION ENTECAVIR
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HBV DNA level and antigen concentration in evaluating liver damage of patients with chronic hepatitis B 被引量:14
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作者 Yao Xie Hui Zhao +1 位作者 Wang-Su Dai Dao-Zhen Xu the Department of Infectious Diseases, Beijing Ditan Hospital. Beijing 100011, China 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2003年第3期418-422,共5页
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
关键词 hepatitis b hepatitis b virus antigen hbeag HbV DNA ALT
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Establishment and preliminery use of hepatitis Bvirus preS1/2 antigen assay 被引量:14
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作者 CHEN Kun, HAN Bao Guang, MA Xian Kai, ZHANG He Qiu, MENG Li, WANG Guo Hua, XIA Fang, SONG Xiao Guo and LING Shi Gan 《World Journal of Gastroenterology》 SCIE CAS CSCD 1999年第6期550-552,共3页
关键词 hepatitis b VIRUS PreS1/*!S2 antigen ELISA hepatitis b E antigen/analysis
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Transformation of hepatitis B serologic markers in babies born to hepatitis B surface antigen positive mothers 被引量:40
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作者 Jian-SheWang HuiChen Qi-RongZhu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第23期3582-3585,共4页
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
关键词 hepatitis b e antigen hepatitis b e antibody hepatitis b Chronic Maternal-infantile transmission hepatitis b surface antigen Children
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Models for predicting hepatitis B e antigen seroconversion in response to interferon-α in chronic hepatitis B patients 被引量:14
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作者 Chang-Tai Wang Ya-Fei Zhang +7 位作者 Bing-Hu Sun Yu Dai Hui-Lan Zhu Yuan-Hong Xu Meng-Ji Lu Dong-Liang Yang Xu Li Zhen-Hua Zhang 《World Journal of Gastroenterology》 SCIE CAS 2015年第18期5668-5676,共9页
AIM:To develop models to predict hepatitis B e antigen(HBe Ag)seroconversion in response to interferon(IFN)-αtreatment in chronic hepatitis B patients.METHODS:We enrolled 147 treatment-nave HBe Agpositive chronic h... AIM:To develop models to predict hepatitis B e antigen(HBe Ag)seroconversion in response to interferon(IFN)-αtreatment in chronic hepatitis B patients.METHODS:We enrolled 147 treatment-nave HBe Agpositive chronic hepatitis B patients in China and analyzed variables after initiating IFN-α1b treatment.Patients were tested for serum alanine aminotransferase(ALT),hepatitis B virus-DNA,hepatitis B surface antigen(HBs Ag),antibody to hepatitis B surface antigen,HBe Ag,antibody to hepatitis B e antigen(anti-HBe),and antibody to hepatitis B core antigen(anti-HBc)at baseline and 12 wk,24 wk,and 52 wk after initiating treatment.We performed univariate analysis to identify response predictors among the variables.Multivariate models to predict treatment response were constructed at baseline,12 wk,and 24 wk.RESULTS:At baseline,the 3 factors correlating most with HBe Ag seroconversion were serum ALT level>4×the upper limit of normal(ULN),HBe Ag≤500 S/CO,and anti-HBc>11.4 S/CO.At 12 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤250 S/CO,decline in HBe Ag>1 log10 S/CO,and anti-HBc>11.8 S/CO.At 24 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤5 S/CO,anti-HBc>11.4 S/CO,and decline in HBe Ag>2 log10 S/CO.Each variable was assigned a score of1,a score of 0 was given if patients did not have any of the 3 variables.The 3 factors most strongly correlating with HBe Ag seroconversion at each time point were used to build models to predict the outcome after IFN-αtreatment.When the score was 3,the response rates at the 3 time points were 57.7%,83.3%,and 84.0%,respectively.When the score was 0,the response rates were 2.9%,0.0%,and 2.1%,respectively.CONCLUSION:Models with good negative and positive predictive values were developed to calculate the probability of response to IFN-αtherapy. 展开更多
关键词 CHRONIC hepatitis b INTERFERON hepatitis b e antigen Treatment Model
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Clinical utility of hepatitis B surface antigen kinetics in treatment-na?ve chronic hepatitis B patients during longterm entecavir therapy 被引量:12
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作者 Tien-Ching Lin Yen-Cheng Chiu +5 位作者 Hung-Chih Chiu Wen-Chun Liu Pin-Nan Cheng Chiung-Yu Chen Ting-Tsung Chang I-Chin Wu 《World Journal of Gastroenterology》 SCIE CAS 2018年第6期725-736,共12页
AIM To investigate the utility of hepatitis B surface antigen(HBsAg) kinetics in chronic hepatitis B patients during long-term entecavir treatment.METHODS This retrospective study included treatment-na?ve chronic hepa... AIM To investigate the utility of hepatitis B surface antigen(HBsAg) kinetics in chronic hepatitis B patients during long-term entecavir treatment.METHODS This retrospective study included treatment-na?ve chronic hepatitis B patients who received at least 2 years of consecutive entecavir treatment. Patients were followed up at three to six month intervals with liver biochemistry, hepatitis B virus DNA, and abdominal sonography. In hepatitis B e antigen(HBeAg)-positive patients, HBeAg levels were assessed every three to six month until results became negative. Serum HBsAg levels were determined at the baseline, oneyear and five-year time points. Liver cirrhosis was diagnosed through liver biopsy, imaging examinations, or clinical findings of portal hypertension. Hepatocellular carcinoma was diagnosed by histological examination or dynamic image studies.RESULTS A total of 211 patients were enrolled. The median treatment time was 5.24(2.00-9.62) years. Multivariate analysis showed that lower baseline HBsAg levels were associated with an earlier virological response, earlier hepatitis B e antigen(HBeAg) seroconversion, and earlier biochemical response in HBeAg-positive patients(cut-off value: 4 log IU/mL) and an earlier virological response in HBeAg-negative non-cirrhotic patients(cut-off value: 2.4 log IU/mL). Although HBsAg levels decreased slowly during long-term entecavir treatment, higher HBsAg decrease rates were found in the first year for HBeAg-positive non-cirrhotic patients, and patients with higher baseline HBsAg levels. More favorable clinical outcomes were not observed by a rapid HBsAg decline per se, but depended on lower baseline HBsAg levels.CONCLUSION Baseline HBsAg can be used to predict treatment responses. HBsAg levels and decrease rates should be considered together according to disease status while interpreting HBsAg changes. 展开更多
关键词 CHRONIC hepatitis b ENTECAVIR hepatitis b e antigen hepatitis b surface antigen KINETICS
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Hepatitis B virus infection:defective surface antigen expression and pathogenesis 被引量:11
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作者 Chun-Chen Wu Ying-shan Chen +2 位作者 Liang Cao Xin-Wen Chen Meng-ji Lu 《World Journal of Gastroenterology》 SCIE CAS 2018年第31期3488-3499,共12页
Hepatitis B virus(HBV) infection is a global public health concern. HBV causes chronic infection in patients and can lead to liver cirrhosis, hepatocellular carcinoma, and other severe liver diseases. Thus, understand... Hepatitis B virus(HBV) infection is a global public health concern. HBV causes chronic infection in patients and can lead to liver cirrhosis, hepatocellular carcinoma, and other severe liver diseases. Thus, understanding HBV-related pathogenesis is of particular importance for prevention and clinical intervention. HBV surface antigens are indispensable for HBV virion formation and are useful viral markers for diagnosis and clinical assessment. During chronic HBV infection, HBV genomes may acquire and accumulate mutations and deletions, leading to the expression of defective HBV surface antigens. These defective HBV surface antigens have been found to play important roles in the progression of HBV-associated liver diseases. In this review, we focus our discussion on the nature of defective HBV surface antigen mutations and their contribution to the pathogenesis of fulminant hepatitis B. The relationship between defective surface antigens and occult HBV infection are also discussed. 展开更多
关键词 hepatitis b SURFACE protein DEFECTIVE SURFACE antigen mutants Endoplasmic reticulum stress FULMINANT hepatitis b OCCULT hepatitis b virus infection PATHOGENESIS
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On-treatment monitoring of liver fibrosis with serum hepatitis B core-related antigen in chronic hepatitis B 被引量:14
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作者 Xiu-Juan Chang Chao Sun +17 位作者 Yan Chen Xiao-Dong Li Zu-Jiang Yu Zheng Dong Wen-Lin Bai Xiao-Dong Wang Zhi-Qin Li Da Chen Wen-Juan Du Hao Liao Qi-Yu Jiang Li-Jun Sun Yin-Yin Li Cui-Hong Zhang Dong-Ping Xu Yong-Ping Chen Qin Li Yong-Ping Yang 《World Journal of Gastroenterology》 SCIE CAS 2019年第32期4764-4778,共15页
BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of h... BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of hepatitis B core-related antigen(HBcrAg)for hepatic histologic changes in patients with chronic hepatitis B(CHB)treated with entecavir.METHODS This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression,respectively,in 403 CHB patients,including 374 with entecavir for 72 weeks(291 underwent paired liver biopsy)and 29 as controls.RESULTS Level of HBcrAg correlated negatively with liver fibrosis staging(γ=-0.357,P<0.001)in hepatitis B e antigen(HBeAg)-positive patients,and positively with liver fibrosis staging in HBeAg-negative patients.Higher HBcrAg concentration was associated with younger age,HBeAg positive status,high HBV DNA loads,high level of hepatitis B surface antigen(HBsAg)and higher necroinflammation,but not with HBV genotype.Serum concentration of HBcrAg,basal core promoter/precore(BCP/PC)mutant,quantitation of HBsAg(qHBsAg)and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression.HBV DNA was undetectable in 88.37%of patients treated with entecavir at week 72,while their level of HBcrAg was still detectable.A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement.HBcrAg concentration>6.33 log IU/mL at baseline and logarithmic reduction>1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement,respectively.CONCLUSION HBcrAg level is associated with liver fibrosis progression.HBcrAg is an excellent monitor of hepatic histological changes,especially in CHB patients treated with nucleoside analogs. 展开更多
关键词 hepatitis b core-related antigen Liver fibrosis Cirrhosis On-treatment monitoring
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Hepatitis B surface antigen levels during natural history of chronic hepatitis B: A Chinese perspective study 被引量:13
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作者 Lin-Yan Zeng Jiang-Shan Lian +9 位作者 Jian-Yang Chen Hong-Yu Jia Yi-Min Zhang Dai-Rong Xiang Liang Yu Jian-Hua Hu Ying-Feng Lu Lin Zheng Lan-Juan Li Yi-Da Yang 《World Journal of Gastroenterology》 SCIE CAS 2014年第27期9178-9184,共7页
AIM: To determine the baseline hepatitis B surface antigen (HBsAg) levels during the different phases of chronic hepatitis B (CHB) patients in China.
关键词 hepatitis b surface antigen quantification Chronic hepatitis b Natural history PERSPECTIVE
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Add-on pegylated interferon augments hepatitis B surface antigen clearance vs continuous nucleos(t)ide analog monotherapy in Chinese patients with chronic hepatitis B and hepatitis B surface antigen≤1500 IU/mL:An observational study 被引量:35
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作者 Feng-Ping Wu Ying Yang +7 位作者 Mei Li Yi-Xin Liu Ya-Ping Li Wen-Jun Wang Juan-Juan Shi Xin Zhang Xiao-Li Jia Shuang-Suo Dang 《World Journal of Gastroenterology》 SCIE CAS 2020年第13期1525-1539,共15页
BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterfero... BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy. 展开更多
关键词 Chronic hepatitis b Peginterferonα-2a Nucleos(t)ide ANALOG hepatitis b surface antigen CLEARANCE hepatitis b surface antigen seroconversion ADD-ON therapy
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Efficacy of telbivudine in HBeAg-positive chronic hepatitis B patients with high baseline ALT levels 被引量:10
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作者 Guo-Cai Lv Wen-Jiang Ma +3 位作者 Lin-Jung Ying Xi Jin Lin Zheng Yi-Da Yang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2010年第32期4095-4099,共5页
AIM:To evaluate the efficacy and safety of telbivudine(LDT) in hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB) patients who have high baseline alanine aminotransferase(ALT) levels between 10 and 20 time... AIM:To evaluate the efficacy and safety of telbivudine(LDT) in hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB) patients who have high baseline alanine aminotransferase(ALT) levels between 10 and 20 times the upper limit of normal.METHODS:Forty HBeAg-positive CHB patients with high baseline ALT levels between 10 and 20 times the upper limit of normal were enrolled and received LDT monotherapy for 52 wk.Another forty patients with baseline ALT levels between 2 and 10 times the upper limit of normal were included as controls.We compared the virological,biochemical,serological and side effect profiles between the two groups at 52 wk.RESULTS:By week 52,the mean decrease in hepatitis B virus(HBV) DNA level compared with baseline was 7.03 log10 copies/mL in the high baseline ALT group and 6.17 log10 copies/mL in the control group,respectively(P < 0.05).The proportion of patients in whom serum HBV DNA levels were undetectable by polymerase chain reaction assay was 72.5% in the high baseline ALT group and 60% in the control group,respectively(P < 0.05).In addition,45.0% of patients in the high baseline ALT group and 27.5% of controls became HBeAg-negative,and 37.5% of those in the high baseline group and 22.5% of controls,respectively,had HBeAg seroconversion(P < 0.05) at week 52.Moreover,in the high baseline group,4 out of 40 patients(10%) became hepatitis B surface antigen(HBsAg)-negative and 3(7.5%) of them seroconverted(became HBsAg-positive).Only 1 patient in the control group became HBsAg-negative,but had no seroconversion.The ALT normalization rate,viral breakthrough,genotypic resistance to LDT,and elevations in creatine kinase levels were similar in the two groups over the 52 wk.CONCLUSION:High baseline ALT level is a strong predictor for optimal results during LDT treatment. 展开更多
关键词 Chronic hepatitis b hepatitis b e antigen Serum alanine aminotransferase level TELbIVUDINE
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Relationship of human leukocyte antigen class II genes with the susceptibility to hepatitis B virus infection and the response to interferon in HBV-infected patients 被引量:28
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作者 Yong-Nian Han Jin-Long Yang Shui-Gen Zheng Qun Tang Wei Zhu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第36期5721-5724,共4页
AIM: To study the relationship of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles with the genetic susceptibility to HBV infection and the response to interferon (IFN) in HBV-infected patients. METHODS: Low... AIM: To study the relationship of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles with the genetic susceptibility to HBV infection and the response to interferon (IFN) in HBV-infected patients. METHODS: Low-resolution DNA typing kit was used to determine HLA-DR-1 and -DQB1 genes in 72 patients with chronic hepatitis B (CHB) and HLA-DRB1 in 200 healthy people ready to donate their bone marrow in Shanghai. Among CHB patients, 35 were treated with IFNα-1b for 24 wk. RESULTS: The frequencies of HLA-DRBI*06, DRBI*08 and DRB1*16 alleles in 72 patients were higher than in 200 healthy people (2.08% vs0%, OR = 3.837, P= 0.018; 11.11% vs5.50%, OR = 2.148, P= 0.034; and 6.94% vs 3.00%, OR = 0.625, P = 0.049, respectively); whereas that of DRBI*07 allele was lower (2.78% vs 7.75%, OR = 0.340, P= 0.046). The frequency of HLA-DRBI* 14 allele was higher in 11 responders to IFN compared with 24 non-responders (18.18% vs2.08%, OR = 10.444, P = 0.031), whereas that of DQBI*07 allele was inverse (9.09% vs37.50%, OR = 0.167, P= 0.021). CONCLUSION: The polymorphism of HLA class II may influence the susceptibility to HBV infection and the response to IFN in studied CHB patients. Compared with other HLA-DRB1 alleles, HLA-DRBI*06, DRBI*08, and DRB1*16 may be associated with chronicity of HBV infection, HLA-DRBI*07 with protection against HBV infection, and HLA-DRB1*14 allele may be associated with a high rate of the response of CHB patients to IFN treatment. Compared with other HLA-DQB1 alleles, HLA-DQBI*07 may be associated with low response rate to IFN. 2005 The WJG Press and Elsevier Inc. All rights reserved 展开更多
关键词 hepatitis b Human leukocyte antigens Geneticsusceptibility INTERFERON
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HBeAg negative variants and their role in the natural history of chronic hepatitis B virus infection 被引量:24
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作者 Alexra Alexopoulou Peter Karayiannis 《World Journal of Gastroenterology》 SCIE CAS 2014年第24期7644-7652,共9页
Molecular virology methods including polymerase chain reaction, cloning and sequencing have revolutionised our understanding of viral genome variation. In the case of hepatitis B virus (HBV), sequencing studies have i... Molecular virology methods including polymerase chain reaction, cloning and sequencing have revolutionised our understanding of viral genome variation. In the case of hepatitis B virus (HBV), sequencing studies have identified a number of virus variants normally found during the natural course of chronic infection. The appearance of the precore stop codon (with G-for-A substitution at position 1896) and basal core promoter (BCP) (with A-for-T and G-for-A, at positions 1762 and 1764, respectively) variants which reduce or abrogate hepatitis B e antigen (HBeAg) production, heralds the initiation of the seroconversion phase from HBeAg to anti-HBe positivity. The gradual removal of the tolerogenic effect of HBeAg leads to the awakening of the immune response (immune clearance phase). Most patients after HBeAg seroconversion become &#x0201c;inactive HBsAg carriers&#x0201d;. However during the course of infection precore and/or BCP variants may emerge and be selected leading to HBeAg negative chronic hepatitis B (CHB) with high viremia levels (reactivation phase). The prevalence of HBeAg negative CHB has been increasing over the last few decades and has become the commonest type of HBV infection in many countries of the world. This probably reflects the aging of existing HBV carriers and the effective prevention measures restricting new HBV infections. Frequent acute exacerbations accompanied by high viral replication, elevated alanine aminotransferase levels and histological activity are a common feature of HBeAg negative CHB leading to cirrhosis much faster than in HBeAg positive CHB patients. 展开更多
关键词 Precore stop codon variants basal core promoter variants hepatitis b e antigen negative chronic hepatitis b Re-activation hepatitis b virus-DNA replication
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