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Hepatitis B cure:Current situation and prospects

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World Journal of Hepatology 2024年第6期16卷 900-911页

作者： Ya-Ping Li Chen-Rui Liu Ling He shuang-suo dang Department of Infectious Diseases The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004Shaanxi ProvinceChina

Achievement of a‘clinical cure’in chronic hepatitis B(CHB)implies sustained virological suppression and immunological control over the infection,which is the ideal treatment goal according to domestic and international CHB management *** practice has shown encouraging results for specific patient cohorts using tailored treatment *** regimens incorporate either nucleos(t)ide analogs,immunomodulatory agents such as pegylated interferonα,or a strategic combination of both,sequentially or concurrently *** these advancements in the clinical handling of hepatitis B,achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment *** include,but are not limited to,the emergence of antiviral resistance,incomplete immune recovery,and the persistence of covalently closed circular ***,the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical *** article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.

关键词： Chronic hepatitis B Clinical cure Polyethylene glycol interferon Treatment strategies Research progress

Prohibitin 1 inhibits cell proliferation and induces apoptosis via the p53-mediated mitochondrial pathway in vitro

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 398-413页

作者： Juan-Juan Shi Yi-Kai Wang Mu-Qi Wang Jiang Deng Ning Gao Mei Li Ya-Ping Li Xin Zhang Xiao-Li Jia Xiong-Tao Liu shuang-suo dang Wen-Jun Wang Department of Infectious Diseases The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi'an 710004Shaanxi ProvinceChina Department of Operating Room The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi'an 710004Shaanxi ProvinceChina

BACKGROUND Prohibitin 1(PHB1)has been identified as an antiproliferative protein that is highly conserved and ubiquitously expressed,and it participates in a variety of essential cellular functions,including apoptosis,cell cycle regulation,prolifera-tion,and *** evidence indicates that PHB1 may play an important role in the progression of hepatocellular carcinoma(HCC).However,the role of PHB1 in HCC is *** To investigate the effects of PHB1 on the proliferation and apoptosis of human HCC cells and the relevant mechanisms in *** HCC patients and healthy individuals were enrolled in this study according to the inclusion and exclusion criteria;then,PHB1 levels in the sera and liver tissues of these participates were determined using ELISA,RT-PCR,and *** HepG2 and SMMC-7721 cells were transfected with the pEGFP-PHB1 plasmid and PHB1-specific shRNA(shRNA-PHB1)for 24-72 *** prolif-eration was analysed with an MTT *** cycle progression and apoptosis were analysed using flow cytometry(FACS).The mRNA and protein expression levels of the cell cycle-related molecules p21,Cyclin A2,Cyclin E1,and CDK2 and the cell apoptosis-related molecules cytochrome C(Cyt C),p53,Bcl-2,Bax,caspase 3,and caspase 9 were measured by real-time PCR and Western blot,*** Decreased levels of PHB1 were found in the sera and liver tissues of HCC patients compared to those of healthy individuals,and decreased PHB1 was positively correlated with low differentiation,TNM stage III-IV,and alpha-fetoprotein≥400μg/*** of PHB1 significantly inhibited human HCC cell proliferation in a time-dependent *** revealed that the overexpression of PHB1 arrested HCC cells in the G0/G1 phase of the cell cycle and induced *** proportion of cells in the G0/G1 phase was significantly increased and the proportion of cells in the S phase was decreased in HepG2 cells that were transfected with pEGFP-PHB1 compar

关键词： Prohibitin 1 Hepatocellular carcinoma cells Apoptosis Cell cycle Mitochondrial pathway

HBV相关肝病患者外周血T细胞及细胞因子水平研究

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世界华人消化杂志 2024年第4期32卷 293-301页

作者：刘晨瑞李亚萍王怡恺张雯郝苗王文俊李婷党双锁西安交通大学第二附属医院感染科陕西省西安市710004

背景乙型肝炎病毒(hepatitis B virus,HBV)相关慢性肝病患者外周血T细胞及细胞因子水平与患者免疫功能状态密切相关,不同疾病程度的HBV相关肝病患者的T细胞、细胞因子水平及与肝病阶段的相关性值得进一步探究.目的探究不同阶段HBV相关... 详细信息

背景乙型肝炎病毒(hepatitis B virus,HBV)相关慢性肝病患者外周血T细胞及细胞因子水平与患者免疫功能状态密切相关,不同疾病程度的HBV相关肝病患者的T细胞、细胞因子水平及与肝病阶段的相关性值得进一步探究.目的探究不同阶段HBV相关慢性肝病患者外周血T细胞亚群计数、细胞因子变化特点及关联性.方法本研究为一项观察性研究,共纳入慢性乙型肝炎(chronic hepatitis B,CHB)患者65例,肝硬化失代偿期(decompensated cirrhosis,DCC)患者122例,肝细胞癌(hepatocellular carcinoma,HCC)患者109例,收集患者一般信息、病史、治疗情况及实验室检查结果、Child-Paugh分级及HCC患者肿瘤巴塞罗那分期,分析各项指标,尤其是T细胞亚群计数及细胞因子的组间差异及特征.结果HBV相关肝硬化、HCC患者外周血CD8^(+)T细胞水平与Child分级A到C呈负相关.HCC患者CD8^(+)T细胞绝对计数显著低于DCC[240(150-379)cells/μLvs 277(154-435)cells/μL,P<0.05]及CHB[240(150-379)cells/μL vs 452(269-706)cells/μL,P<0.001]患者.白细胞介素(interleukin,IL)-6、IL-8、肿瘤坏死因子(tumor necrosis factor,TNF)-α在HCC组均最高.DCC、HCC患者Child-Paugh分级越差,CD3^(+)、CD8^(+)T细胞水平越低,IL-6水平越高.HCC患者CD3^(+)、CD8^(+)T细胞水平随着肿瘤巴塞罗那分期由A到D呈下降趋势,IL-6呈上升趋势.且肝硬化、HCC患者CD3^(+)(r=-0.340,P<0.001)、CD8^(+)(r=-0.353,P<0.001)T细胞水平与IL-6升高水平呈显著负相关.结论HBV相关肝硬化、HCC患者外周血CD8^(+)T细胞计数与Child分级(由A到C)呈负相关,且IL-6水平与CD8^(+)T细胞计数存在负相关关系.

关键词：乙型肝炎病毒肝硬化失代偿期肝细胞癌 T细胞亚群计数细胞因子

VCAN,expressed highly in hepatitis B virus-induced hepatocellular carcinoma,is a potential biomarker for immune checkpoint inhibitors

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World Journal of Gastrointestinal Oncology 2022年第10期14卷 1933-1948页

作者： Mu-Qi Wang Ya-Ping Li Meng Xu Yan Tian Yuan Wu Xin Zhang Juan-Juan Shi shuang-suo dang Xiao-LiJia Department of Infectious Diseases The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004Shaanxi ProvinceChina Department of General Surgery The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004Shaanxi ProvinceChina Department of Critical Care Medicine The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004Shaanxi ProvinceChina

BACKGROUND As a proteoglycan,VCAN exists in the tumor microenvironment and regulates tumor proliferation,invasion,and metastasis,but its role in hepatocellular carcinoma(HCC)has not yet been *** To investigate the expression and potential mechanism of action of VCAN in *** Based on The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset,we explored the correlation between VCAN expression and clinical features,and analyzed the prognosis of patients with high and low VCAN *** potential mechanism of action of VCAN was explored by Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and gene set enrichment *** also explored immune cell infiltration,immune checkpoint gene expression,and sensitivity of immune checkpoint[programmed cell death protein 1(PD-1)/cytotoxic T lymphocyte antigen 4(CTLA4)]inhibitor therapy in patients with different VCAN *** mRNA expression and VCAN methylation in peripheral blood were tested in 100 hepatitis B virus(HBV)-related patients(50 HCC and 50 liver cirrhosis).RESULTS VCAN was highly expressed in HCC tissues,which was associated with a poor prognosis in HCC *** significant difference was found in VCAN mRNA expression in blood between patients with HBV-related cirrhosis and those with HCC,but there was a significant difference in VCAN methylation between the two *** correlation between VCAN and infiltrations of several different tumor immune cell types(including B cells,CD8+T cells,and eosinophils)was significantly *** was strongly related to immune checkpoint gene expression and tumor mutation burden,and could be a biomarker of sensitivity to immune checkpoint(PD1/CTLA4)*** addition,VCAN mRNA expression was associated with hepatitis B e antigen,HBV DNA,white blood cells,platelets,cholesterol,and coagulation *** High VCAN level could be a possible biomarker for poor prognosis of HCC,and its immunomodulatory mechan

关键词： VCAN Hepatocellular carcinoma Hepatitis B virus Immune checkpoints Tumor microenvironment

Inhibitory effect of emodin and Astragalus polysaccharide on the replication of HBV

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World Journal of Gastroenterology 2009年第45期15卷 5669-5673页

作者： shuang-suo dang Xiao-Li Jia Ping Song Yan-An Cheng Xin Zhang Ming-Zhu Sun En-Qi Liu Department of Infectious Diseases the Second Affiliated Hospital of Medical School of Xi'an Jiao Tong University Xi'an 710004 Shannxi Province China The Center of Experimental Animal Xi'an Jiao Tong University Xi'an 710004 Shannxi Province China

AIM: To evaluate the anti-viral effect of emodin plus Astragalus polysaccharide (APS) in hepatitis B virus (HBV) transgenic ***: Sixty HBV transgenic mice (HBV TGM) whose weight varied between 18 and 24 g were randomly divided into 3 groups, with 20 mice in each group. Group A was the normal control, where the mice were treated with physiological saline; group B was the positive control where the mice were treated with lamivudine solution (100 mL/kg per day). Group C was the experimental group where the mice were treated with physiological saline containing emodin and APS (57.59 mg/kg per day and 287.95 mg/kg per day, respectively). The mice were treated daily for 3 wk. After 1 wk recovery time, the mice were sacrifi ced and serum as well as liver tissues were collected for ELISA and histological ***: After 21 d treatment, HBV DNA levels in group B and group C significantly declined when compared with group A (P < 0.05). However, a signif icant increase in HBV DNA content was observed in group B, whereas this phenomenon was not observed in group C. A reduction in the contents of HBsAg, HBeAg and HBcAg in the mice from group B and C was observed when compared with group ***: Emodin and APS have a weak but persistent inhibitory effect on HBV replication in vivo, which may function as a supplementary modality in the treatment of hepatitis B infection.

关键词：病毒复制乙肝病毒黄芪多糖抑制作用大黄素乙型肝炎病毒转基因小鼠 DNA含量

Increased expression of chondroitin sulphate proteoglycans in rat hepatocellular carcinoma tissues

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World Journal of Gastroenterology 2012年第30期18卷 3962-3976页

作者： Xiao-Li Jia Si-Yuan Li shuang-suo dang Yan-An Cheng Xin Zhang Wen-Jun Wang Clare E Hughes Bruce Caterson Department of Infectious Diseases The Second Affiliated Hospital of Medical School of Xi'an Jiaotong University Xi'an 710004 Shaanxi Province China Connective Tissue Biology Laboratories Division of Pathophysiology and Repair School of Biosciences Cardiff University Cardiff Wales CF10 3AX United Kingdom The Institute of Endemic Disease Medical School of Xi'an Jiaotong University Xi'an 710061 Shaanxi Province China

AIM:To investigate the expression of chondroitin sulphate proteoglycans(CSPGs)in rat liver tissues of hepatocellular carcinoma(HCC).METHODS:Thirty male Sprague Dawley rats were randomly divided into two groups:control group(n=10) and HCC model group(n=20).Rats in the HCC model groups were intragastrically administrated with 0.2%(w/v)N-diethylnitrosamine(DEN)every 5 d for 16 wk,whereas 0.9%(w/v)normal saline was administered to rats in the control *** 16 wk from the initiation of experiment,all rats were killed and livers were collected and fixed in 4%(w/v)*** tissues were embedded in paraffin and *** staining(hematoxylin and eosin and Toluidine blue)was performed to demonstrate the onset of HCC and the content of sulphated glycosaminoglycan(sGAG).Immunohistochemical staining was performed to investigate the expression of chondroitin sulphate(CS)/dermatan sulphate(DS)-GAG,heparan sulphate(HS)-GAG,keratan sulphate(KS)-GAG in liver ***,expression and distribution of CSPG family members,including aggrecan,versican,biglycan and decorin in liver tissues,were also immunohistochemically ***:After 16 wk administration of DEN,malignant nodules were observed on the surface of livers from the HCC model group,and their hepatic lobule structures appeared largely disrupted under *** blue staining demonstrated that there was an significant increase in sGAG content in HCC tissues when compared with that in the normal liver tissues from the control group[0.37±0.05 integrated optical density per stained area(IOD/area)and 0.21± 0.01 IOD/area,P<0.05].Immunohistochemical studies demonstrated that this increased sGAG in HCC tissues was induced by an elevated expression of CS/DS(0.28±0.02 IOD/area and 0.18±0.02 IOD/area,P< 0.05)and HS(0.30±0.03 IOD/area and 0.17±0.02 IOD/area,P<0.01)but not KS GAGs in HCC *** studies thereby were performed to investigate the expression and distribution o

关键词：硫酸软骨素蛋白多糖大鼠肝癌组织肝细胞肝癌免疫组化染色糖胺聚糖半定量分析

Real life efficacy and safety of direct-acting antiviral therapy for treatment of patients infected with hepatitis C virus genotypes 1, 2and 3 in northwest China

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World Journal of Gastroenterology 2019年第44期25卷 6551-6560页

作者： Ying Yang Feng-Ping Wu Wen-Jun Wang Juan-Juan Shi Ya-Ping Li Xin Zhang shuang-suo dang Department of Infectious Diseases the Second Affiliated Hospital of Xi’an Jiaotong University

BACKGROUND Regimens involving direct-acting antiviral agents(DAAs)are recommended for the treatment of infection with hepatitis C virus(HCV)genotypes 1,2 and *** real-world data is still not enough,especially in *** To investigate the efficacy and safety of DAA-based regimens in a real-life setting in *** This study included 366 patients infected with HCV genotypes 1,2 and 3,with or without cirrhosis,who were observed between May 2015 and December *** were treated with ledipasvir and sofosbuvir(SOF)(genotype 1)with or without ribavirin(RBV),SOF and RBV(genotype 2),or SOF and daclatasvir(genotype 3),with or without RBV,for 12 or more *** participants’sustained virological responses(SVR)at post-treatment week 12(SVR12)was the primary *** occurrence of adverse events and drug-drug interactions were *** In the 366 patients,genotype 1(59.0%)was the most common genotype,followed by genotypes 2(34.4%)and 3(6.6%).Liver cirrhosis was diagnosed in 154(42.1%)***(13.7%)patients were ***-to-treat analysis revealed that SVR12 was 86.3%(316/366).For modified intention-totreat analysis,SVR12 was achieved in 96.6%of overall patients(316/327),96.3%in patients with genotype 1,97.5%in those with genotype 2,and 95.0%in those with genotype *** of the treatment failures were due to lack of follow-up(3cases had non-responses,1 had virological breakthrough,11 relapsed and 36 did not participate in the follow-up).There was no significant difference in SVR between different genotypes and liver statuses(P0.05 for all).The cumulative hepatocellular carcinoma occurrence and recurrence rate after using the DAAs was 0.9%.Most of the

关键词： Hepatitis C virus Direct-acting antiviral agents Efficacy Safety Drug-drug interactions Real-life experience

Apoptotic bone marrow CD34+ cells in cirrhotic patients

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World Journal of Gastroenterology 2011年第15期17卷 2044-2048页

作者： shuang-suo dang Wen-Jun Wang Ning Gao Shun-Da Wang Mei Li La-Yang Liu Ming-Zhun Sun Tao Dong Department of Infectious Diseases Second Affiliated Hospital of Medical School of Xi’an Jiaotong University 157 Xiwu Road Xi’an 710004 Shaanxi Province China MRC Human Immunology Unit Weatherall Institute of Molecular Medicine John Radcliffe Hospital Oxford OX3 9DS United Kingdom

AIM: To access the frequency and level of apoptotic CD34+ cells isolated from the marrow fluid of patients with post-hepatitis cirrhosis. METHODS: The frequency of bone marrow CD34+ cells and apoptotic bone marrow CD34+ cells in 31 inpatients with post-hepatitis cirrhosis (cirrhosis group), and 15 out-patients without liver or blood disorders (control group) was calculated by flow cytometry. Parameters were collected to evaluate liver functions of patients in cirrhosis group. RESULTS: The percentage of normal bone marrow CD34+ cells was 6.30% ± 2.48% and 1.87% ± 0.53% (t = 3.906, P < 0.01) while that of apoptotic marrowCD34+ cells was 15.00% ± 15.81% and 5.73% ± 1.57% (t = 2.367, P < 0.05) in cirrhosis and control groups, respectively. The percentage of apoptotic marrow CD34+ cells was 6.25% ± 3.30% and 20.92 ± 18.5% (t = 2.409, P < 0.05) in Child-Pugh A and Child-Pugh B + C cirrhotic patients, respectively. The percentage of late apoptotic marrow CD34+ cells was positively correlated with the total bilirubin and aspartate aminotransferase serum levels in patients with cirrhosis. CONCLUSION: The status of CD34+ marrow cells in cirrhotic patients may suggest that the ability of hematopoietic progenitor cells to transform into mature blood cells is impaired.

关键词：细胞凋亡 CD34 骨髓细胞肝硬化患者流式细胞仪谷草转氨酶血液疾病

Facial and bilateral lower extremity edema due to drug-drug interactions in a patient with hepatitis C virus infection and benign prostate hypertrophy: A case report

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World Journal of Clinical Cases 2020年第15期8卷 3372-3376页

作者： Ya-Ping Li Ying Yang Mu-Qi Wang Xin Zhang Wen-Jun Wang Mei Li Feng-Ping Wu shuang-suo dang Department of Infectious Diseases Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004Shaanxi ProvinceChina

BACKGROUND New direct-acting antivirals(DAAs)-based anti-hepatitis C virus(HCV)therapies are highly effective in patients with HCV ***,safety data are lacking regarding HCV treatment with DAAs and drugs for *** SUMMARY Herein,we reported a case of HCV-infection in a 46-year-old man with benign prostatic *** patient received sofosbuvir/velpatasvir as well as methadone maintenance therapy for drug *** viral load became negative at week 1 post *** developed facial and bilateral lower extremity edema 48 h after starting receiving *** disappeared 10 d after treatment with oral furosemide and *** In conclusion,this is the first case of an acute edema in the course of treatment with new DAAs,methadone and *** agents are useful in clinical management of patients with HCV infection,particularly in men with benign prostatic *** should be aware of potential drug-drug interactions in this subset of patients.

关键词： Direct-acting antivirals Hepatitis C virus Sofosbuvir/velpatasvir Drug-drug interactions Case report