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Negative Correlation of Serum hepatitis b Surface Antigen and hepatitis b e Antigen Levels with the Severity of Liver Inflammation in Treatment-naive Patients with chronic hepatitis b virus infection

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Chinese Medical Journal 2017年第22期130卷 2697-2702页

作者： Lu Zhang Ming-Hui Li Wei-Hua Cao Tian-Lin Qi Yao Lu Shu-Ling Wu Hong-Xiao Hao Ge Shen Ru-Yu Liu Lei-Ping Hu Min Chang Wen-Hao Hua Shu-Jing Song Gang Wan Yao Xie Liver Diseases Center Beijing Ditan Hospital Capital Medical University Beijing 100015 China Clinical Test Center Beijing Ditan Hospital Capital Medical University Beijing 100015 China

background： Estimating the grades of liver inflammation is critical in the determination ofantiviral therapy in patients chronically infected with hepatitis b virus （HbV）. The aim of this study was to investigate the correlation ofserum levels of hepatitis b surface antigen （HbsAg） and hepatitis b e antigen （HbeAg） with the liver inflammation grades in treatment-naTve patients with chronic HbV infection. Methods： We retrospectively enrolled 584 treatment-na＇l＇ve HbeAg-positive patients who underwent liver biopsy in Ditan Hospital from January 2008 to January 2016. based on the severity of liver inflammation, the patients were divided into minimal, mild, and moderate groups. SPSS software was used lbr statistical analysis of all relevant data. Results： The liver histological examinations showed that 324, 194, and 66 patients had minimal, mild, and moderate liver inflammation, respectively. The median age of the three groups was 30, 33, and 38 years, respectively （X2 =26.00, P 〈 0.001 ）. The median HbsAg levels in minimal, mild, and moderate inflammation groups were 4.40, 4.16, and 3.67 log U/ml, respectively, and the median HbeAg levels in the three groups were 3.12, 2.99, and 1.86 log sample/cutoff. respectively; both antigens tended to decrease as the grade of inflammation increased （X2 = 99.68 and X2 =99.23, respectively; both P 〈 0.001 ）. The cutoff values of receiver operating characteristic curve in the age, HbsAg and HbeAg levels were 36 years, 4.31 log U/ml, and 2.86 Iog S/CO, respectively, 1 to distinguish minimal grade and other grades of treatment-naTve HbeAg-positive patients with chronic HbV infection. Conclusions： Serum HbsAg and HbeAg quantitation might gradually decrease with aggravated liver inflammation and the corresponding cutoff values rnight help us to distinguish rninimal grades and other grades and detect those who do not need antiviral therapy in treatment-naive HbeAg-positive patients with chronic HbV infection.

关键词： chronic hepatitis b virus infection hepatitis b e Antigen hepatitis b Surface Antigen Liver Inflammation

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Plasmacytoid Dendritic Cell Function and Cytokine Network Profiles in Patients with Acute or chronic hepatitis b virus infection

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Chinese Medical Journal 2018年第1期131卷 43-49页

作者： Ming-Hui Li Lu Zhang Dan Zhang Wei-Hua Cao Tian-Lin Qi Hong-Xiao Hao Xing-Yue Wang Chong-Ping Ran Xiao-Jing Qu Shun-Ai Liu Yao Lu Ge Shen Shu-Ling Wu Min Chang Ru-Yu Liu Lei-Ping Hu Wen-Hao Hua Gang Wan Jun Cheng Yao Xie Liver Diseases Center Beijing Ditan Hospital Capital Medical University Beijing 100015 China Institute of Infectious Diseases Beijing DitanHospitai Capital Medical University Beijing 100015 China Clinical Test Center Beijing Ditan Hospital Capital Medical University Beijing 100015 China

background： Plasmacytoid dendritic cells （pDCs） and cytokines play an important role in occurrence and recovery of hepatitis b virus （HbV） infection. The aim of this study was to explore the frequency and function ofpDC and serum cytokine network profiles in patients with acute or chronic HbV infection. Methods： The healthy individuals （HI group）, hepatitis b envelope antigen （HbeAg）-positive chronic HbV patients in immune tolerance （IT） phase （IT group）, HbeAg-positive chronic HbV patients （CHb group）, and acute HbV patients （AHb group） were enrolled in this study. The frequency of cluster of differentiation antigen 86 （CD86）＋ pDC and the counts of CD86 molecular expressed on surface ofpDC were tested by flow cytometer. The quantitative determinations ofcytokines, including Fins-like tyrosine kinase 3 ligand （FIt-3L）, interferon （1FN）-α2, IFN-γ, interleukin （IL）-17A, IL-6, IL-10, transforming growth factor （TGF）-β1 and TGF-β2, were performed using Luminex multiplex technology. Results： In this study, there were 13 patients in HI group, 30 in IT group, 50 in CHb group, and 32 in AHb group. Compared with HI group, HbV infected group （including all patients in IT, CHb and AHb groups） had significantly higher counts of CD86 molecular expressed on the surface ofpDC （4596.5 ± 896.5 vs. 7097.7 ± 3124.6; P 〈 0.001）. The counts of CD86 molecular expressed on the surface of pDC in Crib group （7739.2 ±4125.4） was significantly higher than that of IT group （6393.4 ± 1653.6, P=0.043）. Compared with IT group, the profile of cytokines of FIt-3L, IFN-γ, and IL-17A was decreased, IFN-α2 was significantly increased （P =0.012） in CH b group. The contents of IL-10, TGF-{31, and TGF-132 in AHb group were significantly increased compared with IT and CHb groups （all P 〈 0.05）. Conclusions： This study demonstrated that the function of pDC was unaffected in HbV infection. The enhanced function of pDC and IFN-α2 might involve triggering the immune response from IT to hepatitis active phase in H bV infection. Acute patients mainly presen

关键词： Acute hepatitis b virus infection chronic hepatitis b virus infection Interferon-α2 Interleukin-10 PlasmacytoidDendritic Cells

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New therapeutic options for persistent low-level viremia in patients with chronic hepatitis b virus infection:Increase of entecavir dosage

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World Journal of Gastroenterology 2021年第8期27卷 666-676页

作者： Guo-Qing Yin Jun Li bei Zhong Yong-Fong Yang Mao-Rong Wang Department of Infectious Diseases Nanjing Zhong-Da HospitalSoutheast University School of MedicineNanjing 210009Jiangsu ProvinceChina Department of Infectious Diseases The First Affiliated Hospital with Nanjing Medical UniversityNanjing 210029Jiangsu ProvinceChina The Sixth Affiliated Hospital Guangzhou Medical University/Qingyuan People’s HospitalQingyuan 511518Guangdong ProvinceChina Department of Liver Disease The Second Hospital of NanjingNanjing University of Chinese MedicineNanjing 210003Jiangsu ProvinceChina Department of Infectious Diseases and Liver Disease Center The Affiliated Nanjing Jinling HospitalNanjing UniversityNanjing 210002Jiangsu ProvinceChina

chronic hepatitis b virus(HbV)infection(CHb)is a public health concern worldwide.Current therapies utilizing nucleos(t)ide analogs(NA)have not resulted in a complete cure for CHb.Furthermore,patients on long-term NA treatment often develop low-level viremia(LLV).Persistent LLV,in addition to causing the progression of liver disease or hepatocellular carcinoma,may shed light on the current plight of NA therapy.Here,we review the literature on LLV,NA treatment,and various doses of entecavir to find a strategy for improving the efficacy of this antiviral agent.For LLV patients,three therapeutic options are available,switching to another antiviral monotherapy,interferon-αswitching therapy,and continuing monotherapy.In real-world clinical practice,entecavir overdose has been used in antiviral therapy for CHb patients with NA refractory and persistent LLV,which encouraged us to conduct further in-depth literature survey on dosage and duration related entecavir studies.The studies of pharmacodynamics and pharmacokinetics show that entecavir has the maximal selected index for safety,and has great potential in inhibiting HbV replication,in all of the NAs.In the particular section of the drug approval package published by the United States Food and Drug Administration,entecavir doses 2.5-20 mg/d do not increase adverse events,and entecavir doses higher than 1.0 mg/d might improve the antiviral efficacy.The literature survey led us to two suggestions:(1)Increasing entecavir dose to 1.0 mg/d for the treatment of NA naïve patients with HbV DNA>2×106 IU/mL is feasible and would provide better prognosis;and(2)Further research is needed to assess the long-term toxic effects of higher entecavir doses(2.5 and 5.0 mg/d),which may prove beneficial in treating patients with prior NA treatment,partial virological response,or LLV state.

关键词： chronic hepatitis b virus infection Low-level viremia Therapeutic options Entecavir Dose Efficacy

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b cell dysfunction in chronic hepatitis b virus infection

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Liver Research 2021年第1期5卷 11-15页

作者： Lijie Ma Xuehua Sun Xiaoni Kong Yueqiu Gao Institute of Clinical Immunology Department of Liver DiseasesShuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina

chronic hepatitis b(CHb)remains a global health problem.The persistence of hepatitis b surface antigen(HbsAg)in the blood for longer than 6 months after the initial infection is a sign of CHb.The therapeutic goal for the functional cure of CHb is the generation of antibodies against HbsAg.However,the adaptive immune response of patients with CHb cannot generate an efficient antiviral response.Many previous studies have evaluated T cell function and T cell therapy specifically designed to counter hepatitis b virus(HbV)infection.As one of the major components of adaptive immunity,b cells also display dysfunctions in anti-HbsAg antibody(HbsAb)production and antigen presentation.Patients with CHb have amplification of CD19^(+)CD10^(-)CD27^(-)CD21^(-)atypical memory b cell subsets and CD19^(+)CD24^(hi)CD38^(hi) regulatory b cells.Currently,no reviews have summarized specific b cell responses during CHb infection.Thus,in this study,we summarized b cell dysfunction during CHb progression and the potential mechanisms behind these dysfunctions to further our understanding of the mechanisms of adaptive immune response of b cells in the process of CHb development and help provide new methods and ideas for the treatment of CHb.

关键词： chronic hepatitis b virus infection b cell dysfunction hepatitis b surface antibody Atypical memory b cells(atMbCs) Antigen-presenting cells(APCs) Regulatory b cells(bregs)

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baseline hepatocyte ballooning is a risk factor for adverse events in patients with chronic hepatitis b complicated with nonalcoholic fatty liver disease

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World Journal of Hepatology 2023年第2期15卷 237-254页

作者： You-Wen Tan Jia-Min Wang Xing-bei Zhou Department of Hepatology The Third Hospital of Zhenjiang Affiliated Jiangsu UniversityZhenjiang 212003Jiangsu ProvinceChina

bACKGROUND Although many studies have investigated the impact of chronic hepatitis b virus(HbV)infection and nonalcoholic fatty liver disease(NAFLD)on liver disease,few have investigated the relationship between nonalcoholic steatohepatitis(NASH)defined by liver pathology and the prognosis of chronic HbV infection.Most patients were followed up for a short time.This study aimed to further explore the impact of NAFLD and the pathological changes confirmed by liver pathology in patients with chronic HbV infection.AIM To study the effect of NAFLD confirmed using liver pathology on the outcomes of long-term serious adverse events[cirrhosis,hepatocellular carcinoma(HCC),and death]in patients with chronic hepatitis b(CHb)virus infection.METHODS We enrolled patients with chronic hepatitis b virus(HbV)infection who underwent liver biopsy at the Third People’s Hospital of Zhenjaing Affiliated Jiangsu University between January 2005 and September 2020.baseline clinical and pathological data on liver pathology and clinical data at the end of follow-up were collected.Propensity score matching(PSM)was used to balance baseline parameters,Kaplan-Meier(K-M)survival analysis was used to evaluate the risk of clinical events,and Cox regression was used to analyze the risk factors of events.RESULTS Overall,456 patients with chronic HbV infection were included in the study,of whom 152(33.3%)had histologically confirmed NAFLD.The median follow-up time of the entire cohort was 70.5 mo.Thirty-four patients developed cirrhosis,which was diagnosed using ultrasound during the follow-up period.K-M survival analysis showed that NAFLD was not significantly associated with the risk of cirrhosis(log-rank test,P>0.05).Patients with CHb with fibrosis at baseline were more prone to cirrhosis(log-rank test,P=0.046).After PSM,multivariate analysis showed that diabetes mellitus,ballooning deformation(bD),and platelet(PLT)were independent risk factors for cirrhosis diagnosed using ultrasound(P<0.05).A total of 10 patients(2.2%)developed HCC,and six of

关键词： Nonalcoholic fatty liver disease Steatohepatitis chronic hepatitis b virus infection Hepatocellular carcinoma Cirrhosis

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Emerging Trends in Epidemiology of hepatitis b virus infection

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Journal of Clinical and Translational Hepatology 2017年第3期5卷 272-276页

作者： Cristina Stasi Caterina Silvestri Fabio Voller Observatory of Epidemiology Regional Health Agency of Tuscany Florence Italy Department of Experimental and Clinical Medicine University of Florence Florence Italy Observatory of Epidemiology Regional Health Agency of Tuscany Florence Italy

Although a vaccine against hepatitis b virus (HbV) has been available since 1982,the prevalence of adults with chronic HbV infection in sub-Saharan Africa and East Asia is still estimated at 5-10%.A high rate of chronic infections is also found in the Amazon and the southern parts of eastern and central Europe.In the Middle East and the Indian subcontinent,the prevalence is 2-5%.Less than 1% of the population of Western Europe and North America is chronically infected.Given the high prevalence of infections (such as hepatitis) among inmates,prison is considered a reservoir for facilitating such infections.based on these premises,this current review examines and discusses emerging trends in the epidemiology of HbV infection,with particular attention to HbV infection in prison.The hepatitis b surface antigen (HbsAg) prevalence in prisoners in west and central Africa is very high (23.5%).The Centers for Disease Control and Prevention has highlighted the importance of HbV blood screening and subsequent anti-HbV vaccination in the prison population.The vaccination was recommended for all inmates,representing an opportunity to prevent HbV infection in a high-risk population.In these subjects,an accelerated hepatitis b immunisation schedule may result in rapid seroconversion for early short-term protection.Therefore,it is necessary to seek collaboration among public health officials,clinicians and correctional authorities to implement a vaccination programme.

关键词： chronic hepatitis b virus infection Public health Anti-HbV vaccine Epidemiology Prison

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