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Trends in Mortality of cirrhosis in china: An Analysis of the china Death Surveillance Database from 2008 to 2020

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Journal of clinical and Translational Hepatology 2024年第3期12卷 236-244页

作者： Xiaoxiao Wang Huixin Liu Jinlei Qi Lijun Wang Peng Yin Feng Liu Lai Wei Yu Wang Maigeng Zhou Huiying Rao Peking University People’s Hospital Peking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijing International Cooperation Base for Science and Technology on NAFLD DiagnosisBeijingChina Department of clinical Epidemiology and Biostatistics Peking University People’s HospitalBeijingChina National center for chronic Noncommunicable Disease control and Prevention Chinese Center for Disease Control and PreventionBeijingChina Beijing Tsinghua changgung Hospital Tsinghua UniversityBeijingChina chinese Foundation for hepatitis Prevention and control BeijingChina

Background and Aims:china accounts for 14.9%of total cirrhosis deaths worldwide.A detailed and comprehensive understanding of the contemporary status of cirrhosis mortality in china is crucial for establishing strategies for intervention and decreasing the disease burden of cirrhosis *** study aimed to report the cirrhosis mortality rates in our whole country or province over ***:Mortality data from 2008 to 2020 were retrieved from the Disease Surveillance Point System(DSPs)of the chinese center for Disease control and *** crude mortality rate and age-standardized mortality rate of patients with cirrhosis were stratified by sex,residential location,and *** average annual percentage change(AAPc)in cirrhosis mortality rates from 2008 to 2020 was also ***:The crude mortality rate of cirrhosis was 4.57/100,000 people in *** with females and individuals living in urban areas,males and people living in rural areas had greater age-standardized *** crude mortality rate and age-standardized mortality rate in provinces in Southwest china(Guangxi,Yunnan,Guizhou,and Qinghai)were greater than those in other ***,with increasing age,the age-specific mortality rate increased *** 2008 to 2020,the mortality rate of cirrhosis in china decreased except for in males aged 50–59 years,females aged 45–49 years and females aged 80–84 ***:The mortality rate of patients with cirrhosis in china decreased from 2008 to *** the future,interventions of cirrhosis mortality control need to pay more attention to all males,females aged 45–49 and 80–84 years,and people living in rural areas and in provinces in Southwest china.

关键词： cirrhosis Mortality Trend china

Mortality Burden of liver cancer in china: An Observational Study From 2008 to 2020

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Journal of clinical and Translational Hepatology 2024年第4期12卷 371-380页

作者： Huixin Liu Xiaoxiao Wang Lijun Wang Peng Yin Feng Liu Lai Wei Yu Wang Maigeng Zhou Jinlei Qi Huiying Rao Department of clinical Epidemiology and Biostatistics Peking University People's HospitalBeijingChina Peking University People’s Hospital Peking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijing International Cooperation Base for Science and Technology on NAFLD DiagnosisBeijingChina National center for chronic Noncommunicable Disease control and Prevention Chinese Center for Disease Control and PreventionBeijingChina Beijing Tsinghua changgung Hospital Tsinghua UniversityBeijingChina chinese Foundation for hepatitis Prevention and control BeijingChina

Background and Aims:china accounts for nearly half of liver cancer deaths globally.A better understanding of the current liver cancer mortality will be helpful to establishing priorities for intervention and to decreasing the disease burden of liver *** study aimed to explore and predict the mortality burden of liver cancer in ***:Data were extracted from the Disease Surveillance Point system of the chinese center for Disease control and Prevention from 2008 to *** and age-standardized liver cancer mortality rates were reported by sex,urban or rural residence,and *** in liver cancer mortality rates from 2008 to 2020 were estimated as average annual percentage change(AAPc).The changing trend of live cancer mortality in the future is also ***:In 2020,the crude mortality of liver cancer was 25.57/100,000,and males and people lived in rural areas had higher age-standardized liver cancer mortality rates than females and people lived in people in urban *** mortality and age-standardized mortality rates in southwest provinces(Guangxi,Sichuan,Tibet)and in a northeast province(Heilongjiang)were higher than that in other provinces,and age-specific mortality rates increased with *** 2008 to 2020,liver cancer mortality rates decreased,but people under 50 years of age had a higher AAPc than those over 50 years of age,possibly because of the adoption of hepatitis B virus vaccination in newborns and ***,the mortality of liver cancer in 2021–2030 is predicted to have a downward ***:liver cancer mortality rates declined in china from 2008 to *** interventions to control liver cancer mortality need to focus on people of male sex,older age,and living in rural areas or less developed provinces.

关键词： liver cancer Mortality Burden Trend china Prediction

Precore mutation enhances viral replication to facilitate persistent infection especially in HBeAg-negative patients

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Virologica Sinica 2024年第2期39卷 319-330页

作者： Guixin Li Danli Yang Xin Liu Ting Zhang Hui Liu Jun Zou Zimeng Xu Xiangmei chen Lizhong Dai Hongsong chen Fengmin Lu Peking University People's Hospital Peking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijing International Cooperation Base for Science and Technology on NAFLD DiagnosisBeijing100044China Department of Microbiology and Infectious Disease center School of Basic Medical SciencesPeking UniversityBeijing100191China Baruch S.Blumberg Institute DoylestownPA18901USA Shenzhen Sanyuansheng Biotechnology co. LtdShenzhen518000China Precision Medicine center of Zhengzhou University Academy of Medical SciencesZhengzhou UniversityZhengzhou450001China Peking University-Sansure Biotech Joint laboratory of Molecular Medicine Sansure Biotech Co.LtdChangsha410205China

Naturally occurred precore(Pc,G1896A)and/or basal core promoter(BcP,A1762T/G1764A)mutations are prevalent in chronic HBV-infected patients,especially those under HBeAg-negative ***,the replicative capacity of HBV with Pc/BcP mutations remains ***,meta-analysis showed that,only under HBeAg-negative status,the serum HBV DNA load in patients with Pc mutation was 7.41-fold higher than those without the *** Pc mutation alone and BcPþPc mutations promoted HBV replication in cell and hydrodynamic injection mouse *** human hepatocyte chimeric mouse model,BcPþPc mutations led to elevated replicative capacity and intrahepatic core protein ***,prec RNA harboring Pc mutation could serve as mRNA to express core and P proteins,and such pgRNA-like function favored the maintenance of cccDNA pool under HBeAg-negative ***,BcPþPc mutations induced more extensive and severe human hepatocyte damage as well as activated endoplasmic reticulum stress and TNF signaling pathway in livers of chimeric *** study indicates that HBeAg-negative patients should be monitored on HBV mutations regularly and are expected to receive early antiviral treatment to prevent disease progression.

关键词： hepatitis B virus Precore mutation Basal core promoter mutations Endoplasmic reticulum stress

cD4^+cXcR5^+ T cells activate cD27^+IgG^+ B cells via IL-21 in patients with hepatitis c virus infection

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Hepatobiliary & Pancreatic diseases International 2016年第1期15卷 55-64页

作者： Fan-Yun Kong Bo Feng Heng-Hui Zhang Hui-Ying Rao Jiang-Hua Wang Xu cong Lai Wei Peking University People’s Hospital Peking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases

BAcKGROUND： chronic hepatitis c virus （HcV） infection causes the skewing and activation of B cell subsets, but the characteristics of IgG＋ B cells in patients with chronic hepa- titis c （cHc） infection have not been thoroughly elucidated. cD4＋cXcR5＋ follicular helper T （Tfh） cells, via interleukin （IL）-21 secretion, activate B cells. However, the role of cD4＋cXcR5＋ T cells in the activation ofIgG＋ B cells in cHc patients is not clear. METHODS： The frequency of IgG＋ B cells, including cD27-IgG＋ B and cD27＋IgG＋ B cells, the expression of the activation markers （cD86 and cD95） in IgG＋ B cells, and the percentage of circu- lating cD4＋cXcR5＋ T cells were detected by flow cytometry in cHc patients （n=70） and healthy controls （n=25）. The con- centrations of serum IL-21 were analyzed using ELISA. The role of cD4＋cXcR5＋ T cells in the activation of IgG＋ B cells was investigated using a co-culture system. RESULTS： A significantly lower proportion of cD27＋IgG＋ B cells with increased expression of cD86 and cD95 was observed in cHc patients. The expression of cD95 was negatively correlated with the percentage of cD27＋IgG＋ B cells, and it contributed to cD27＋IgG＋ B cell apoptosis. circulating cD4＋cXcR5＋ T cells and serum IL-21 were significantly increased in cHc patients. Moreover, circulating cD4＋cXcR5＋ T cells from cHc patients induced higher expressions of cD86 and cD95 in cD27＋IgG＋ B cells in a co-culture system; the blockade of the IL-21 decreased the expression levels of cD86 and cD95 in cD27＋IgG＋ B ***： HcV infection increased the frequency of cD4＋cXcR5＋ T cells and decreased the frequency of cD27＋IgG＋ B cells. cD4＋cXcR5＋ T cells activated cD27＋IgG＋ B cells via the secretion of IL-21.

关键词： chronic hepatitis c IgG+ B cells cD4+cXcR5+ T cells

Recovery of natural killer cells is mainly in post-treatment period in chronic hepatitis c patients treated with sofosbuvir plus ledipasvir

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World Journal of Gastroenterology 2018年第40期24卷 4554-4564页

作者： Xiao-Xiao Wang Bi-Fen Luo Han-Ji Jiang Xu cong Qian Jin Dan-Li Ma Lai Wei Bo Feng Peking University Hepatology Institute Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases Peking University People's Hospital

AIM To investigate how natural killer(NK) cells are affected in the elimination of hepatitis c virus(HcV) by sofosbuvir/ledipasvir, two highly effective direct-acting antivirals(DAAs). METHODS Thirteen treatment-na?ve and treatment-experienced chronic hepatitis c(cHc) patients were treated with sofosbuvir/ledipasvir, and NK cells were detected at baseline, weeks 2, 4, 8 and 12 during therapy, and week post of treatment(Pt)-12 and 24 after the end of therapy by multicolor flow cytometry and compared with those from 13 healthy controls. RESULTS All patients achieved sustained virological response. There was a significant decline in cD56^(bright) NK cell frequencies at week 8(P = 0.002) and week 12(P = 0.003), which were altered to the level comparable to healthy controls at week Pt-12, but no difference was observed in the frequency of cD56^(dim) NK cells. compared with healthy controls, the expression levels of NKG2A, NKp30 and cD94 on NK cells from cHc patients at baseline were higher. NKG2A, NKp30 and cD94 started to recover at week 12 and reached the levels similar to those of healthy controls at week Pt-12 or Pt-24. Before treatment, patients have higher interferon(IFN)-γ and perforin levels than healthy controls, and IFN-γ started to recover at week 8 and reached the normalized level at week Pt-12. cONcLUSION NK cells of cHc patients can be affected by DAAs, and phenotypes and function of NK cells recover not at early stage but mainly after the end of sofosbuvir/ledipasvir treatment.

关键词： Direct-acting antivirals therapy hepatitis c virus Natural killer cells Natural killer subsets

Effect of spleen operation on antiviral treatment in hepatitis cvirus-related cirrhotic patients

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World Journal of Gastroenterology 2014年第41期20卷 15387-15397页

作者： Bo Feng Wei Zhang Bi-Fen Luo Guang-Jun Song Jian Wang Qian Jin Hong Qin Lai Wei Peking University People’s Hospital Peking University Hepatology Institute Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases

AIM: To investigate the impact of spleen operation (SO) on interferon-α (IFN-α)-based antiviral treatment in patients with hepatitis c virus (HcV)-related cirrhosis.

关键词： hepatitis c virus cirrhosis Interferon Ribavirin Splenectomy Partial splenic embolization

Emerging antivirals for the treatment of hepatitis B

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World Journal of Gastroenterology 2014年第24期20卷 7707-7717页

作者： Xue-Yan Wang Hong-Song chen Peking University Hepatology Institute Peking University People’s Hospital Beijing key laboratory of hepatitis c and immunotherapy for liver diseases

chronic infection with hepatitis B virus(HBV)constitutes a major global public health threat,causing substantial disease burdens such as liver cirrhosis and hepatocellular carcinoma,thus representing high unmet medical *** available therapies are safe,well tolerated,and highly effective in decreasing viremia and improving measured clinical outcomes with low rates of antiviral ***,long-term management remains a clinical challenge,mainly due to the slow kinetics of HBV surface antigen *** this article,we review emerging antivirals directed at novel targets derived from mechanisms of viral cellular entry,viral replication,viral assembly,and the host immune response,leading to preclinical and clinical trials for possible future therapeutic *** recent therapeutic advances in the development of all categories of HBV inhibitors may pave the way for regimens of finite duration that result in long-lasting control of chronic hepatitis B infection.

关键词： hepatitis B Antiviral Nucleoside analogue Nucleotide analogue Non-nucleoside antivirals

An Ideal Hallmark closest to complete cure of chronic hepatitis B Patients:High-sensitivity Quantitative HBsAg Loss

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Journal of clinical and Translational Hepatology 2023年第1期11卷 197-206页

作者： Zi-Long Wang Jia-Rui Zheng Rui-Feng Yang Lin-Xiang Huang Hong-Song chen Bo Feng Peking University People’s Hospital Peking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijingChina

In the era of antiviral therapy,the main goal of treatment has shifted from the persistent inhibition of hepatitis B virus(HBV)replication to the pursuit of serological clearance of HBs surface antigen(HBsAg).Based on the life cycle of HBV,HBsAg originates from covalently closed circular DNA(cccDNA)and integrated HBV DNA,thus reflecting their transcriptional *** HBsAg loss may mean elimination or persistent inactivity of the HBV genome including cccDNA and integrated HBV *** loss improves the recovery of abnormal immune function,which in turn,may further promote the clearance of residual *** with functional cure and the great improvement of clinical outcomes,the continuous seroclearance of high-sensitivity quantitative HBsAg may represent the complete cure of chronic hepatitis B(cHB).For many other risk factors besides HBV itself,patients with HBsAg loss still need regular *** this review,we summarized the evolution of cHB treatment,the origin of serum HBsAg,the pattern of HBsAg seroclearance,and the effect of HBsAg loss on immune function and disease *** addition,we discuss the significance of high-sensitivity HBsAg detection and its possibility as a surrogate of complete cure.

关键词： hepatitis B virus chronic hepatitis B HBsAg Immunoassay Functional cure complete cure Biomarker

HBsAg stimulates NKG2D receptor expression on natural killer cellsand inhibits hepatitis c virus replication

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Hepatobiliary & Pancreatic diseases International 2018年第3期17卷 233-240页

作者： Xiao-Xiao Wang Xiao-Ben Pan Jin-chao Han Xu cong Qian Jin Xiang-Sha Kong Lai Wei Bo Feng Peking University People’s Hospital Peking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesNo.11 Xizhimen South StreetBeijing 100044China

Background： Higher hepatitis B surface antigen （HBsAg） facilitates hepatitis c virus （HcV） clearance inpatients with hepatitis B virus （HBV）/HcV co-infection. We investigated the effect of exogenous HBsAgon the... 详细信息

关键词： hepatitis B surface antigen hepatitis c virus Natural killer cells NKG2D