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Effect of IFNα-2a on Fas expression and apoptosis rate of peripheral blood cytotoxic T cells in patients with hepatitis B

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Hepatobiliary & Pancreatic diseases International 2005年第3期4卷 403-405页

作者： institute of infectious diseases, zhejiang university school of medicine, hangzhou 310003, china (Hou W, Liu KZ, Li MW and Wo JE) institute of infectious diseases Zhejiang University School of Medicine Hangzhou 310003 China.

Interferon(IFN) with antiviral and im-munomodulatory activities is one of the most important therapeutic agents for the treatment of chronic hepatitis. The apoptotic effect of IFN is influenced by cell type and the types of IFN, which suppresses proliferation and induces apoptosis in some cell types while inhibiting apoptosis in others. The aim of this study was to explore the effect of IFNα-2a on Fas expression and the apoptosis rate of peripheral blood cytotoxic T cells (CTLs) in patients with hepatitis B. METHODS:Peripheral blood mononuclear cells were isolated from 26 patients with hepatitis B including 16 patients with chronic hepatitis B and 10 patients with chronic severe hepatitis B. Fas expression and apoptosis rate of CTLs were analyzed with flow cytometry before and after IFNα-2a treatment. RESULTS:Before IFNα-2a treatment, Fas expression and apoptosis rate of CTLs from patients with chronic hepatitis B were significantly higher than those from patients with chronic severe hepatitis B and healthy controls respectively. No significant difference was observed between Fas expression and apoptosis rate of CTLs from patients with chronic severe hepatitis B and healthy controls. After IFNα-2a treatment,Fas expression and apoptosis rate of CTLs from different groups were compared with those before IFNα-2a treatment, showing no significant difference despite alternation of different degree. CONCLUSIONS:Activation induced cell death (AICD) exists in peripheral blood CTLs from patients with hepatitis B. No effect of IFNα-2a exerts on Fas expression and apoptosis rate of Fas in patients with hepatitis B.

关键词： IFNα-2a hepatitis B cytotoxic T cells Fas activation induced cell death

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Chinese Clinical Practice Guidelines for the Prevention and Treatment of Mother-to-Child Transmission of Hepatitis B Virus(Version 2024)

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infectious Microbes & diseases 2024年第3期6卷 108-116页

作者： Jinfeng Liu Qinglei Zeng Fanpu Ji Hong Ren Wenhong Zhang Lanjuan Li Yingren Zhao infectious diseases Physicians Branch of Chinese Medical Doctor Association Chinese Society of infectious diseases of Chinese Medical Association The First Affiliated Hospital of Xi’an Jiaotong university Xi’anChina Shaanxi Clinical Medical Research Center of infectious diseases Xi’anChina The First Affiliated Hospital of Zhengzhou university ZhengzhouChina The Second Affiliated Hospital of Xi’an Jiaotong university Xi’anChina The Second Affiliated Hospital of Chongqing Medical university ChongqingChina Huashan Hospital Fudan UniversityShanghaiChina State Key Laboratory for the Diagnosis and Treatment of infectious diseases The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina 不详

The Chinese Clinical Practice Guidelines for the prevention and treatment ofmother-to-child transmission of hepatitis B virus,developed by the Chinese Society of infectious diseases of the Chinese Medical Association in 2019,serves as a valuable reference for standardizing the process of preventing mother-to-child transmission in *** new evidence emerges,it is crucial that timely and regular updates are made to the clinical practice guidelines so as to optimize guidance for clinical practice and *** this end,the infectious Disease Physician Branch of Chinese Medical Doctor Association and the Chinese Society of infectious diseases of Chinese Medical Association,in collaboration with multidisciplinary experts,have updated the guidelines based on the latest domestic and international research advancements and clinical practice,in order to provide guidance and reference for clinicians andmaternal and child healthcare workers.

关键词： guidelines hepatitis B virus mother-to-child transmission prevention treatment update

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Advances in cell sources of hepatocytes for bioartificial liver

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Hepatobiliary & Pancreatic diseases International 2012年第6期11卷 594-605页

作者： Xiao-Ping Pan , Lan-Juan Li State Key Laboratory for Diagnosis and Treatment of infectious diseases, First Affiliated Hospital, zhejiang university school of medicine, hangzhou 310003, china State Key Laboratory for Diagnosis and Treatment of infectious diseases First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND: Orthotopic liver transplantation (OLT) is the most effective therapy for liver failure. However, OLT is severely limited by the shortage of liver donors. Bioartificial liver (BAL) shows great potential as an alternative therapy for liver failure In recent years, progress has been made in BAL regarding genetically engineered cell lines, immortalized human hepatocytes, methods for preserving the phenotype of primary human hepatocytes, and other functional hepatocytes derived from stem cells. DATA SOURCES: A systematic search of PubMed and ISI Web of Science was performed to identify relevant studies in English language literature using the Key words such as liver failure bioartificial liver, hepatocyte, stem cells, differentiation, and immortalization. More than 200 articles related to the cell sources of hepatocyte in BAL were systematically reviewed. RESULTS: Methods for preserving the phenotype of primary human hepatocytes have been successfully developed. Many genetically engineered cell lines and immortalized human hepatocytes have also been established. Among these cell lines the incorporation of BAL with GS-HepG2 cells or alginate encapsulated HepG2 cells could prolong the survival time and improve pathophysiological parameters in an animal model of liver failure. The cBAL111 cells were evaluated using the AMC-BAL bioreactor, which could eliminate ammonia and lidocaine, and produce albumin. Importantly, BAL loading with HepLi-4 cells could significantly improve the blood biochemical parameters, and prolong the survival time in pigs with liver failure. Other functional hepatocytes differentiated from stem cells, such as human liver progenitor cells, have been successfully achieved. CONCLUSIONS: Aside from genetically modified liver cell lines and immortalized human hepatocytes, other functionalhepatocytes derived from stem cells show great potential as cell sources for BAL. BAL with safe and effective liver cells may be achieved for clinical liver fa

关键词： bioartificial liver liver failure hepatocyte liver cell source stem cell differentiation immortalization

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Hepatitis C virus infection and biological falsepositive syphilis test:a single-center experience

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Hepatobiliary & Pancreatic diseases International 2011年第4期10卷 399-402页

作者： Wei-Fang Zhu,Shui-Ying Lei and Lan-Juan Li State Key Laboratory for Diagnosis and Treatment of infectious diseases Key Laboratory of infectious diseases,zhejiang Province Department of infectious diseases,First Affiliated Hospital,zhejiang university school of medicine,hangzhou 310003,china State Key Laboratory for Diagnosis and Treatment of infectious diseases Key Laboratory of infectious diseases Zhejiang Province Department of infectious diseases First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:Rapid plasma regain positive and/or treponema pallidum hemagglutination negative [RPR(+)/TPHA(-)] results were designated as biologic false-positive (BFP).There are limited data about BFP reactions against syphilis in patients with hepatitis C virus (HCV) *** study aimed to determine the prevalence of BFP reactions for syphilis in patients with HCV infection in a large sample and assess the relationship between BFP reactions and HCV ***:A total of 2656 patients with positive anti-HCV and 5600 healthy control subjects were enrolled in this *** C serology was determined by a second generation ELISA test for HCV *** serology was determined by the RPR *** subjects with reactive RPR positive underwent the TPHA *** and laboratory data were collected by trained ***:Among 2656 patients,111 (4.2%) had a reactive RPR *** the 111 patients who were subjected to reactive RPR test,30 (27.0%) showed HCV(+)/RPR(+).Of 5600 healthy controls,80 (1.4%) had a reactive RPR *** (17.5%) controls with HCV(-)/RPR(+) had a non-reactive TPHA *** represented 1.1% of all HCV-positive and 0.3% of all HCV-negative subjects (P0.05).CONCLUSIONS:The data of this study demonstrate that HCV infection is associated with a false-positive RPR *** this study BFPs were significantly more common in HCV positive patients compared to HCV-negative *** abnormality can be considered as a predictor for *** BFPs must be considered in assessing the frequency of syphilis in a

关键词： hepatitis C virus biological false-positive syphilis

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Expression of A, G and B melanoma antigen genes in human hepatocellular carcinoma

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Hepatobiliary & Pancreatic diseases International 2002年第4期1卷 570-573页

作者： Zhi Chen Jun-Bing Shao Wei Wu the institute of infectious diseases, First Affiliated Hospital, zhejiang university school of medicine, hangzhou 310003, china institute of infectious diseases First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China. chenzhi@***

Objective: To observe the expression of the A melano- ma antigen (MAGE), G melanoma antigen (GAGE) and B melanoma antigen (BAGE) genes in human hepatocellular carcinoma cell lines. Methods: The MAGE-1, MAGE-3, GAGE1-8, GAGE1-2 and BAGE mRNA lever in hepatocellular carcinoma cell lines SMMC-7721, QQY-7701, BEL- 7402 were studied by reverse transcription polymer- ase chain reaction and were compared with biopsied liver tissues. Results: MAGE-1 and BAGE mRNA were expressed in SMMC-7721, MAGE-3 and BAGE in QGY-7701, MAGE-1 and GAGE1-2 in BEL-7402. None of these genes was expressed in biopsied liver tissues. Conclusions: MAGE-1, MAGE-3, GAGE1-8, GAGE1-2 and BAGE were expressed in hepatocellu- lar carcinoma cell lines, respectively. These tumor- specific antigens can be used as molecular markers and possible targets of immunotherapy for patients with hepatocellular carcinoma.

关键词： B melanoma antigen G melanoma antigen A melanoma antigen hepatocellular carcinoma

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Current therapy with nucleoside/nucleotide analogs for patients with chronic hepatitis B

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Hepatobiliary & Pancreatic diseases International 2006年第3期5卷 350-359页

作者： Xiao-Wei Xu and Ya-Gang Chen Department of infectious diseases, First Affiliated Hospital, zhejiang university school of medicine, hangzhou 310003, china Department of infectious diseases First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310006 China.

BACKGROUND: Currently, more and more nucleos(t)ide analogs are appearing as therapeutic options in the treatment of chronic hepatitis B (CHB). Their efficacy and safety profile in hepatitis B virus (HBV) infection have already been studied in detail worldwide. This review summarizes the efficacy of lamivudine, adefovir, entecavir and newer antiviral agents such as emtricitabine, telbivudine and clevudine in the treatment of hepatitis B in different clinical situations. DATA SOURCES: An English-language literature search using OVID and MEDLINE was performed and a total of 40 articles on the treatment of chronic hepatitis with nucleos(t)ide analogues were selected. RESULTS: Nucleos(t)ide analogs such as lamivudine, adefovir and entecavir are well tolerated and induce a decrease in serum HBV-DNA levels associated with normalization of serum alanine aminotransferase (ALT) levels. But their sustained response with HBeAg to anti-HBe seroconversion is rarely obtained and HBsAg loss is exceptional. The response is maintained during therapy which needs to be continued indefinitely in the majority of patients since withdrawal of treatment is generally followed by a rapid reactivation of hepatitis B. However, drug resistant mutations can be induced in long-term treatment. Other newer antiviral agents such as emtricitabine, telbivudine and clevudine in the treatment of hepatitis B are still under phaseⅡorⅢclinical trials. CONCLUSIONS: Nucleos(t)ide analogs play an important role in the therapy of hepatitis B now and in the future. Lamivudine is limited by the frequent emergence of drugresistant (HBV) mutants (YMDD). Adefovir and entecavir appear to be effective against both YMDD mutation and wild type. Therapeutic options against hepatitis B virus remain a major clinical challenge.

关键词： hepatitis B antivirus lamivudine adefovir entecavir emtricitabine telbivudine clevudine

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Key challenges to the development of extracorporeal bioartificial liver support systems

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Hepatobiliary & Pancreatic diseases International 2012年第3期11卷 243-249页

作者： Li-Fu Zhao, Xiao-Ping Pan and Lan-Juan Li State Key Laboratory for Diagnosis and Treatment of infectious diseases, First Affiliated Hospital, zhejiang university school of medicine, hangzhou 310003, china State Key Laboratory for Diagnosis and Treatment of infectious diseases First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND: For nearly three decades, extracorporeal bioartificial liver (BAL) support systems have been anticipated as promising tools for the treatment of liver failure. However, these systems are still far from clinical application. This review aimed to analyze the key challenges to the development of BALs. DATA SOURCE: We carried out a PubMed search of Englishlanguage articles relevant to extracorporeal BAL support systems and liver failure. RESULTS: Extracorporeal BALs face a series of challenges. First, an appropriate cell source for BAL is not readily available. Second, existing bioreactors do not provide in vivolike oxygenation and bile secretion. Third, emergency needs cannot be met by current BALs. Finally, the effectiveness of BALs, either in animals or in patients, has been difficult to document. CONCLUSIONS: Extracorporeal BAL support systems are mainly challenged by incompetent cell sources and flawed bioreactors. To advance this technology, future research is needed to provide more insights into interpreting the conditions for hepatocyte differentiation and liver microstructure formation.

关键词： bioartificial liver liver failure cell source bioreactor

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In vitro cleavage of hepatitis B virus C mRNA by 10-23 DNA enzyme

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Hepatobiliary & Pancreatic diseases International 2005年第4期4卷 573-576页

作者： Wei Hou, Jian-Er Wo, Min-Wei Li and Ke-Zhou Liu institute of infectious diseases, First Affiliated Hospital, zhejiang university school of medicine, hangzhou 310003, china institute of infectious diseases First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China.

BACKGROUND: 10-23 DNA enzyme is one kind of de-oxyribozymes for RNA cleavage. The inhibition effects of 10-23 DNA enzyme on the expression of the HBV C gene in HepG2. 2. 15 cells were demonstrated previously. The aim of this study was to further explore the cleavage activities of 10-23 DNA enzyme targeting at HBV C gene mRNA in vitro. METHODS: 10-23 DNA enzyme named Drz-HBV-C-9 specific to HBV C gene ORF A1816UG was designed and synthesized. HBV C gene mRNA was obtained by the in vitro transcription method. Cleavage activities of Drz-HBV-C-9 were observed in vitro. Values of kinetic parameters including Km,Kcat and Kcat/Km were calculated accordingly. RESULTS: Under the certain cleavage conditions, Drz-HBV-C-9 could efficiently cleave target mRNA at specific sites in vitro. Cleavage products of 109nt plus 191nt were obtained. The kinetic parameters, Km,Kcat and Kcat/ Km for Drz-HBV-C-9, were 1.4 ×10-9 mol, 1.6 min-1 and 1.1 × 109 mol-1 · min-1, respectively. CONCLUSIONS: 10-23 DNA enzyme targeting at HBV C gene mRNA possesses specific cleavage activities in vitro. This would be a potent antiviral strategy with respect to HBV gene therapy.

关键词： 10-23 DNA enzyme hepatitis B C gene cleavage in vitro

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Prevalence of hepatitis B and C in HIV-infected patients:a meta-analysis

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Hepatobiliary & Pancreatic diseases International 2011年第2期10卷 122-127页

作者： Jia-Jia Chen, Cheng-Bo Yu, Wei-Bo Du and Lan-Juan LiState Key Laboratory for Diagnosis and Treatment of infectious diseases, First Affiliated Hospital, zhejiang university school of medicine, hangzhou 310003, china State Key Laboratory for Diagnosis and Treatment of infectious diseases First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND: Hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share similar routes of transmission by sexual intercourse or drug use by parenteral injection, so coinfection is common. This study aimed to determine the prevalence of coinfection with either HCV or HBV in patients infected with HIV. DATA SOURCES: A meta-analysis was performed to quantify HBV coinfection with HCV in HIV patients. Published studies in the English and Chinese language medical literature involving cohorts of HIV patients concomitantly infected with HBV and/or HCV were collected from the PubMed database, ISI Web of Science, the Cochrane library clinical trials registry, CNKI (china National Knowledge Infrastructure) and Google Scholar, for relevant articles before November 2009. The search was conducted with the following key words:hepatitis C, HCV, hepatitis B, HBV, human immunodeficiency virus, HIV, and coinfection. Data were extracted from relevant studies by two investigators. RevMan 5.0 software was used to perform the meta-analysis. RESULTS: We identified 22 studies involving 17 664 patients. Substantial differences in the HCV rate compared to the HBV rate in HIV patients were found in the overall analysis [odds ratio (OR)=3.00; 95% confidence interval (CI) 1.90-4.73]. A subgroup analysis showed similar results in a European group, but not in Asian or African groups. However, a meta-analysis between HIV+HBV+HCV+ and HIV+HBV+HCV-patients showed no significant difference (OR=0.91; 95% CI 0.57-1.45). Although subgroup analysis still lacked essential differences, different regions seemed to have different patterns. CONCLUSIONS: HCV-HIV coinfection is more frequent than HBV-HIV coinfection overall. However, HCV infection does not affect the prevalence of HBV infection in HIV-positive patients.

关键词： hepatitis B virus hepatitis C virus human immunodeficiency virus coinfection meta-analysis

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Gene heterogeneity of hepatitis B virus isolates from patients with severe hepatitis B

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Hepatobiliary & Pancreatic diseases International 2005年第4期4卷 530-534页

作者： Wei Wu, Yu Chen, Bing Ruan and Lan-Juan Li hangzhou, china Department of infectious diseases, First Affiliated Hospital, zhejiang university school of medicine, Key Laboratory of infectious diseases of Health Ministry of china, hangzhou 310003, china Department of infectious diseases First Affiliated Hospital Zhejiang University School of Medicine Key Laboratory of Infectious Diseases of Health Ministry of China Hangzhou 310003 China.

BACKGROUND: The pathogenesis of severe hepatitis B remains unknown. Reports have indicated that hepatitis B virus (HBV) mutations are important factors in the pathogenesis of this disease. This study was to investigate the genetic heterogeneity of HBV strains from serum samples of patients with fulminant hepatitis B. METHODS: Full-length HBV genomes from 4 patients with severe hepatitis B were cloned and sequenced to observe mutations in every open reading-frame ( ORF). Serum samples of another 25 patients with severe hepatitis B, 30 patients with chronic hepatitis B, and 25 HBV carriers were collected for sequencing and comparison of mutations in preS2, preC and core promoter regions. RESULTS: Of 4 HBV full-length genome sequences, 3 had a G to A mutation at nucleotide A1896 in the preC region and 1 had double mutations of T1762-A1764 in the core promoter region. The 4 sequences showed mutations in the known B or T cell epitopes of the preS2 and C regions. For the other 3 groups, more mutations were seen in the preS2 region in the HBV isolates from the patients with severe hepatitis B than those from the patients with chronic hepatitis B and HBV carriers (P <0.01). There was a significant difference of mutations in the T cell epitope region of preS2 between the patients with severe hepatitis B and those with chronic hepatitis B or HBV carriers (P <0.01). In the preC and core promoter regions, the mutation frequencies of T1653 and C1753 were 48.0% and 24.0% respectively in the patients with severe hepatitis B, but none of these mutations were observed in the patients with chronic hepatitis B group or HBV carriers (P <0.01). The mutation frequency of T1762-A1764 was 76.0% in the patients with severe hepatitis B, 40.0% in the patients with chronic hepatitis B (P <0. 01) , and 16. 0% in the HBV carriers ( P < 0. 01). There was a significant difference in A1896 mutation between the patients with severe hepatitis B and the patients with chronic hepatitis B (P < 0. 05 ) o

关键词： hepatitis B virus severe hepatitis virus genome gene heterogeneity preS2 preC core promoter

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