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New perspective on the natural course of chronic hbv infection

Frontiers of Medicine 2014年第2期8卷 129-134页

作者： Yong-Yuan Zhang Ke-Qin Hu Zhongping Duan HB Vtech LLC 13901 Lullaby RD Germantown MD 20874 USA Division of Gastroenterology and Hepatology University of California Irvine School of Medicine Orange CA 92868 USA You An Hospital Capital Medical University Beijing 100069 China

chronic hepatitis B virus （hbv） infection is a significant threat to public health and an enormous burden on society. Mechanisms responsible for chronic hbv infection remain poorly understood. A better understanding of the natural course of chronic hbv infection may shed new light on the mechanisms underlying this disease and help in designing new antiviral strategies. Natural course of chronic hbv infection is conventionally viewed as an uninterrupted process that is usually marked by hbv e antigen （HBeAg） seroconversion or characterized by different phases associated with assumed host responses to hbv infection. However, none of these descriptions captures or highlights the core events that determine the natural course of chronic hbv infection. In this review, we briefly present the current knowledge on this subject and explain the significance and implication of events that occur during infection. A pre-core mutant becomes predominant in the viral population following elimination of the wild-type virus in duck hepatitis B virus-chronically infected animals. The coupled events in which first there is viral clearance that clears wild-type virus and then there is the reinfection of wild-type virus cleared livers with mutant virus are highly relevant to understanding of the natural course of chronic hbv infection under both treated and untreated conditions. In our new perspective, a general natural course of chronic hbv infection comprises cycles of viral clearance and reinfection, and such cycles prolong the chronic hbv infection course. Reviewing published data on the natural course of chronic hbv infection can reduce the possibility of missing important points in the initial data interpretation.

关键词： hepatitis B virus chronic hbv infection natural course hepatitis B seroconversion

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The Expression of CD2 in chronic hbv infection

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Cellular & Molecular Immunology 2008年第1期5卷 69-73页

作者： Jie Li Baotai Qi Ping Chen Linjing He Ping Wang Yuqiang Ji Ming Xie Department of Pathogenic Microbiology and Immunology Medical School of Xi＇an Jiaotong University Xi＇an 710061 China

It was previously reported that several kinds of intercellular adhesion molecules are closely related to chronic hbv infection. The complex of CD2 and CD58 plays an important role in enhancing the adhesion of T lymphocytes to target cells, and promoting hyperplasia and activation of T lymphocytes. In this study, we detected the level of CD2 expressed on the surface of PBMC, the expression level of CD2 mRNA in PBMC and the percentage of CD2 positive cells in PBMC of patients with chronic hbv infection and compared them with the expression level of normal controls. We also determined the level of serum hbv DNA from patients with chronic hbv infection and from normal controls. The clinical characteristics of hepatic function were tested as well. The results showed that the expression of CD2 significantly increased with the severity of chronic hbv infection, which suggested that CD2 might contribute to the hepatocyte damage in chronic hbv infection. Cellular ＆ Molecular Immunology.

关键词： chronic hbv infection CD2 RT-PCR

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Efficiency and safety of lamivudine therapy in patients with chronic hbv infection, dialysis or after kidney transplantation

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World Journal of Gastroenterology 2005年第3期11卷 400-402页

作者： Tadeusz Wojciech Lapinski Robert Flisiak Jerzy Jaroszewicz Ma3gorzata Michalewicz Oksana Kowalczuk Department of Infectious Diseases Institute of Molecular Biology

AIM: To analyze the effectiveness and safety of lamivudine treatment in patients with chronic hbv infection undergoing hemodialysis or after kidney transplantation, and to study the frequency of tyrosine - methionine - aspartate - aspartate (YMDD) mutation occurrence after lamivudine treatment. METHODS: We analyzed 91 patients with chronic hepatitis B, among whom, 16 patients underwent hemodialysis, 7 patients had kidney transplantation and 68 patients had normal function of kidney. The hemodialysis patients were treated by lamivudine 300 mg/wk. patients after kidney transplantation and patiente with normal function of kidney were treated with lamivudine 100 mg/d. Therapy lasted for 12 mo. hbv-DNA, HBsAg, HBeAg and anti-HBe, and anti-HCV antibodies were assessed in sera of patients. The analysis was performed before and 6 mo after the end of lamivudine treatment. Before, during and after the lamivudine therapy, the number of erythrocytes, leukocytes, platelets and hemoglobin concentration, ALT and AST activity, as well as bilirubin, urea and creatinine concentrations were analyzed in sera from patients. RESULTS: After the 12-mo lamivudine treatment, elimination of hbv - DNA was observed in 56% patients undergoing hemodialysis and in 53% patients with normal kidney function. Only 1 from 7 (14%) kidney-transplanted patients eliminated hbv-DNA. Furthermore, HBeAg elimination was observed in 36% hemodialysis patients, in 51% patients with normal function of kidneys and in 43% kidney transplanted patients. Among the patients undergoing dialysis, no YMDD mutation was found after 12 mo of therapy, while it was detected in 9 patients (13%) with normal function of kidney and in 2 kidney-transplanted patients (29%, P<0.006). We did not observe significant side effecte of lamivudine treatment in studied patiente. CONCLUSION: Effectiveness of lamivudine therapy in dialysis patients is comparable with that in patiente with normal function of kidney. Lamivudine treatment is well

关键词： chronic hbv infection Lamivudine Kidney transplantation Hemodialysis

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The role of PGE2 in chronic hbv infection

The role of PGE2 in chronic HBV infection

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第十二届全国免疫学学术大会

作者： Li Xiaoyan Xu Yong Xie Tingting Gao Lifen Ma Chunhong Liang Xiaohong Key Laboratory of infection and Immunity of Shandong Province Department of ImmunologySchool of MedicineShandong University

Background:chronic hepatitis B(CHB) infection is still a major global health *** more than 250 million people are chronically infected with hbv and each year a growing number of patients die of chronic hbv infection related liver cirrhosis and hepatocellular carcinomad *** immune response was deemed to play a crucial role in the chronicity of ***2 has a paradoxical role in immune responses,acting as both a proinflammatory mediator and a potent immunosuppressant,especially in tumor and chronic infection to limit the functions of natural killer(NK) cells and *** and Results:Here,we found that,compared with that in healthy donors,serum prostaglandin E2(PGE2) level were significantly upregulated in patients with chronic hepatitis *** analysis showed that serum PGE2 level was negatively correlated with the production of granzymeB and perforin by CD8T cells and positively correlated with the expression of Tim3 on CD8 *** vivo experiment based on the AAV/hbv1.2 model,using PGE2 analogs showed that intraperitoneal injection of PGE2 analogues significantly increased HBsAg and pgRNA *** cytometry analysis of hepatic mononuclear cells showed that PGE2 analogs inhibits the secretion of IFN-γ-and TNF-α by CD8T *** vitro experiments showed that PGE2 did not affect viral replication of ***:These results suggest that PGE2 might involve in the chronicity of hbv ***,PGE2 blockade would be a promising therapeutic candidate for the intervention of CHB.

关键词： chronic hbv infection prostaglandin E2 CD8+T cells

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Antibiotic-induced gut bacteria depletion has no effect on hbv replication in hbv immune tolerance mouse model

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Virologica Sinica 2023年第3期38卷 335-343页

作者： Yanan Bu Kaitao Zhao Zaichao Xu Yingcheng Zheng Rong Hua Chuanjian Wu Chengliang Zhu Yuchen Xia Xiaoming Cheng State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology Hubei Jiangxia LaboratoryInstitute of Medical VirologyTaiKang Center for Life and Medical SciencesTaiKang Medical SchoolWuhan UniversityWuhan430071China Department of Clinical Laboratory Renmin Hospital of Wuhan UniversityWuhan430060China Department of Pathology Center for Pathology and Molecular DiagnosticsHubei Clinical Center and Key Laboratory of Intestinal and Colorectal DiseasesZhongnan Hospital of Wuhan UniversityTaiKang Medical SchoolWuhan UniversityWuhan430071China

Commensal microbiota is closely related to Hepatitis B virus(hbv)*** bacteria maturation accelerates hbv immune clearance in hydrodynamic injection(HDI)hbv mouse ***,the effect of gut bacteria on hbv replication in recombinant adeno-associated virus(AAV)-hbv mouse model with immune tolerance remains *** aim to investigate its role on hbv replication in AAV-hbv mouse model.C57BL/6 mice were administrated with broad-spectrum antibiotic mixtures(ABX)to deplete gut bacteria and intravenously injected with AAV-hbv to establish persistent hbv *** microbiota community was analyzed by fecal qPCR assay and 16S ribosomal RNA(rRNA)gene *** replication markers in blood and liver were determined by ELISA,qPCR assay and Western blot at indicated time *** response in AAV-hbv mouse model was activated through HDI of hbv plasmid or poly(I:C)and then detected by quantifying the percentage of IFN-γ^(+)/CD8^(+)T cells in the spleen via flow cytometry as well as the splenic IFN-γmRNA level via qPCR *** found that antibiotic exposure remarkably decreased gut bacteria abundance and *** treatment failed to alter the levels of serological hbv antigens,intrahepatic hbv RNA transcripts and HBc protein in AAV-hbv mouse model,but contributed to HBsAg increase after breaking of immune ***,our data uncovered that antibiotic-induced gut bacteria depletion has no effect on hbv replication in immune tolerant AAV-hbv mouse model,providing new thoughts for elucidating the correlation between gut bacteria dysbiosis by antibiotic abuse and clinical chronic hbv infection.

关键词： Hepatitis B virus(hbv) Gut bacteria Antibiotic mixtures(ABX) Adeno-associated virus(AAV)-hbv mouse model Persistent hbv replication chronic hbv infection

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Macrophage Phenotypes and Hepatitis B Virus infection

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Journal of Clinical and Translational Hepatology 2020年第4期8卷 424-431页

作者： Yujia Li Shilin Li Xiaoqiong Duan Chunhui Yang Min Xu Limin Chen Institute of Blood Transfusion Chinese Academy of Medical Sciences and Peking Union Medical CollegeChengduSichuanChina Toronto General Research Institute University of TorontoTorontoON M5G 1L6Canada

Globally, hepatitis B virus (hbv) infection and its related liver diseases account for 780,000 deaths every year. Outcomes of hbv infection depend on the interaction between the virus and host immune system. It is becoming increasingly apparent that Kupffer cells (KCs), the largest population of resident and monocyte-derived macrophages in the liver, contribute to hbv infection in various aspects. These cells play an important role not only in the anti-hbv immunity including virus recognition, cytokine production to directly inhibit viral replication and recruitment and activation of other immune cells involved in virus clearance but also in hbv outcome and progression, such as persistent infection and development of end-stage liver diseases. Since liver macrophages play multiple roles in hbv infection, they are directly targeted by hbv to benefit its life cycle. In the present review, we briefly outline the current advances of research of macrophages, especially the studies of their phenotypes, in chronic hbv infection.

关键词： Hepatitis B virus chronic hbv infection Macrophage Phenotype

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Fitting logistic regression models to assess vitamin D deficiency with clinical parameters in chronic hepatitis B patients

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Infectious Disease Modelling 2021年第1期6卷 612-617页

作者： Freshteh Osmani Ghodsiyeh Azarkar Department of Biostatistics and Epidemiology Faculty of HealthBirjand University of Medical SciencesBirjandIran Infectious Disease Research Center Birjand University of Medical SciencesBirjandIran

Statistical models provide a quantitative structure with which clinicians can evaluate their hypotheses to explain patterns in observed data and generate *** contrast,vitamin D is an important immune modulator that plays an emerging role in liver diseases such as chronic hepatitis B(CHB).Therefore,we quantified 25(OH)D_(3) serum levels in 292 CHB patients tested for their association with clinical *** 292 patients,69(63%),95(47%),and 39(19%)had severe vitamin D deficiency(25(OH)D_(3)hbv patients(52%).Vitamin D deficiency was observed in most CHB ***,our results recommend that substitution of vitamin D can be a substitution method in the treatment of patients with hbv-associated disorders.

关键词： Vitamin D deficiency Data-mining chronic hbv infection

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Antiviral Therapy of Liver Cirrhosis Related to Hepatitis B Virus infection

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Journal of Clinical and Translational Hepatology 2014年第3期2卷 197-201页

作者： Lun-Gen Lu Department of Gastroenterology Shanghai First People's Hospital Shanghai Jiaotong University School of Medicine Shanghai China

Hepatitis B virus (hbv) infection is a leading cause of liver disease worldwide,with 75% of those affected distributed in the Asia-Pacific *** one million hbv-infected patients die of liver cirrhosis and hepatocellular carcinoma (HCC) each *** left untreated,6-20% of chronic hepatitis B (CrHB) patients will develop cirrhosis over five *** cumulative incidence of hbv-related cirrhosis,disease progression,and prognosis are closely associated with serum hbv DNA *** therapy in hbv-related cirrhosis has been documented by several long-term cohort studies to decrease disease progression to hepatic decompensation and *** approval and availability of oral antiviral agents with better safety profiles has greatly improved the prognosis for hbv-related ***,we discuss the significance of antiviral therapy for hbv-related cirrhosis and the management of hbv-related diseases in the future.

关键词： Hepatitis B virus chronic hbv infection Liver cirrhosis Antiviral therapy

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Perilipin2 inhibits the replication of hepatitis B virus deoxyribonucleic acid by regulating autophagy under high-fat conditions

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World Journal of Virology 2023年第5期12卷 296-308页

作者： Chuang Wang Xiao-Yun Gao Mei Han Meng-Chun Jiang Xiao-Yi Shi Chun-Wen Pu Xuan Du Graduate School Graduate School of Dalian Medical UniversityDalian 116000Liaoning ProvinceChina Department of Geriatric The Second Affiliated Hospital of Dalian Medical UniversityDalian 116023Liaoning ProvinceChina Department of Gastroenterology The Second Affiliated Hospital of Dalian Medical UniversityDalian 116023Liaoning ProvinceChina Dalian Public Health Clinical Center Dalian Municipal Research Institute for Public HealthDalian 116001Liaoning ProvinceChina

BACKGROUND chronic hepatitis B virus(hbv)infection is often associated with increased lipid deposition in ***,when combined with non-alcoholic fatty liver disease or hyperlipidemia,it tends to have a lower hbv deoxyribonucleic acid(DNA)*** relationship between lipid metabolism and hbv DNA replication and its underlying mechanisms are not well *** To investigate the relationship between lipid metabolism and hbv DNA replication and its underlying *** 1603 HBsAg-seropositive patients were included in the *** first explored the relationship between patients'lipid levels,hepatic steatosis,and hbv DNA ***,we constructed an hbv infection combined with a hepatic steatosis cell model in vitro by fatty acid stimulation of HepG2.2.15 cells to validate the effect of lipid metabolism on hbv DNA replication in *** knocking down and overexpressing Plin2,we observed whether Plin2 regulates autophagy and hbv *** inhibiting both Plin2 and cellular autophagy under high lipid stimulation,we examined whether the Plin2-autophagy pathway regulates hbv *** The results revealed that serum triglyceride levels,high-density lipoprotein levels,and hepatic steatosis ratio were significantly lower in the hbv-DNA high load *** regression analysis indicated that hepatic steatosis and serum triglyceride levels were negatively correlated with hbv-DNA *** analysis by HBeAg showed significant negative correlations between hbv-DNA load and hepatic steatosis ratio in both HBeAgpositive and HBeAg-negative *** in vitro cell model was developed by stimulating HepG2.2.15 cells with palmitic acid and oleic acid to study the relationship between hbv-DNA load and lipid *** results of the in vitro experiments suggested that fatty acid treatment increased lipid droplet deposition and decreased the expression of cell supernatant HBsAg,HBeAg,and hbv DNA *** blot and polymerase c

关键词： Lipid metabolism chronic hbv infection Nonalcoholic fatty liver Plin2 Autophagy

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Modeling and Simulation for Dynamics of Anti-hbv infection Therapy

Modeling and Simulation for Dynamics of Anti-HBV Infection T...

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The International Conference on Automation and Robotics(ICAR 2011)

作者： Xiao Chen Lequan Min Yongan Ye Yu Zheng Automation School University of Science and Technology Beijing Mathematics and Physics School University of Science and Technology Beijing Traditional Chinese Internal Medicine Key Laboratory of China Education Ministry Dongzhimen Hospital Beijing University of Chinese Medicine

Based on our previous researches, this paper introduces a new differential equation model to describe the dynamics of traditional Chinese medicines（TCM） + nucleoside analogues（NA） anti-hbv infection treatment for the chronic hepatitis B（CHB） patients. This model has five state variables. A treatment-activated specific term in this model is in charge of directly clearing patients’ hbv rather than damaging patients’ hepatocytes. As an application, we use this model to simulate the dynamics of TCM + NA anti-hbv infection personalized combination treatments. The numerical simulations and analysis show that the TCM+ NA combination treatments are able to activate patients’ abilities of cytokine-midiated noncytolytic hbv clearance.

关键词： chronic hbv infection Mathematical modeling Basic virus reproductive number Global stability Numerical simulation

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