哈维·J·阿尔特（ Harvey J. Alter ）近十年来的部分研究成果 诸平 王庆浩博主在《 2020诺贝尔生理医学奖原创探索之旅 》博文中指出：1970年哈维·J·阿尔特（ Harvey J. Alter ） 与其同事开始研究输血患者的肝炎发病率，1972年他们在Ann Intern Med发表了研究结果。3年之后的1975年Harvey J. Alter与其同事在N Engl J Med发表论文，报告了输血相关性肝炎不是由于甲肝和乙肝引起的。同年Harvey J. Alter与其同事在Lancet发表论文，报告输血相关肝炎的临床和血清学分析，有8例是“非A非B（非甲肝非乙肝）”肝炎。1978年Alter和他的同事们发现，这些肝炎患者的血液可能会把这种疾病传染给黑猩猩。这说明这种输血性肝炎具有传染性。Alter的系统研究发现了一种新的独特的慢性病毒性肝炎，Alter小组称其为“非A、非B”型肝炎（起初命名类似非典，后来命名为丙肝）。如果从1970年算起，至今已经有50年了， 哈维·J·阿尔特在探索丙肝病毒研究的征程中，他类似于马拉松长跑的领跑者，与他人合作，接力赛跑，50年如一日，至今奔跑 前进的步伐从未减慢。看看近十年的新作，方知进入 耄耋 之年的 哈维·J·阿尔特是怎样对待科学研究，怎样对待丙肝研究的。 Time for the Elimination of Hepatitis C Virus as a Global Health Threat John W. Ward, Alan R. Hinman, Harvey J. Alter 2020,The Liver -Chapter This chapter reviews the health burden of hepatitis C virus (HCV) infection, the process for development of HCV elimination goals, the successes and challenges in the implementation of interventions t ... more Reflections on the History of HCV: A Posthumous Examination Harvey J. Alter , Patrizia Farci, Jens Bukh, Robert H. Purcell 2020,Clinical Liver Disease -Article A microarray-based pathogen chip for simultaneous molecular detection of transfusion–transmitted infectious agents Valeria De Giorgi, Huizhi Zhou, Harvey J. Alter , Robert D. Allison 2019,Journal of Translational Medicine -Article BACKGROUND: New and emerging transfusion-transmitted infections remain a threat to the blood supply. Blood donors are currently screened for less than half of known agents, primarily by individual tes ... more No Observed Risk of Pregnancy and Maternal-Fetal Transmission of Zika Virus Following Blood Transfusion Valeria DeGiorgi, Jennifer Tan, Sarah Fowler, Sonia Maciejewski, David Gordon, Harvey J. Alter , Robert D Allison 2019,Research Square -Preprint BACKGROUND: Zika virus (ZIKV) is primarily mosquito-borne, but can also be transfusion- and sexually transmitted. Maternal-fetal transmission may result in fetal loss or severe congenital defects. MET ... more Interpretation of pathogen load in relationship to infectivity and pathogen reduction efficacy Jeffrey McCullough, Harvey J. Alter , Paul M. Ness 2019,Transfusion -Article Is Elimination of Hepatitis B and C a Pipe Dream or Reality? Harvey J Alter , Francis V Chisari 2019,Gastroenterology -Article From B to Non-B to C: The Hepatitis C Virus in Historical Perspective Harvey J. Alter 2019,HCV: The Journey from Discovery to a Cure -Chapter The discovery of HCV was an evolutionary process beginning with the serendipitous identification of the Australia antigen that later proved to be the surface protein of the hepatitis B virus (HBV) and ... more Binding of Free and Immune Complex‐\Associated Hepatitis C Virus to Erythrocytes Is Mediated by the Complement System Kazi Abdus Salam, Richard Y. Wang, Teresa Grandinetti, Valeria Giorgi, Harvey J. Alter , Robert D. Allison 2018,Hepatology -Article Erythrocytes bind circulating immune complexes (ICs) and facilitate IC clearance from the circulation. Chronic hepatitis C virus (HCV) infection is associated with IC-related disorders. In this study, ... more Circulating let-7 levels in serum correlate with the severity of hepatic fibrosis in chronic hepatitis C Kentaro Matsuura, Nobuhiro Aizawa, Hirayuki Enomoto, Shuhei Nishiguchi, Hidenori Toyoda, Takashi Kumada, Etsuko Iio, Kyoko Ito, Shintaro Ogawa, Masanori Isogawa, Harvey J Alter , Yasuhito Tanaka 2018,Open Forum Infectious Diseases -Article Background: Evaluating the progression of hepatic fibrosis in chronic hepatitis C (CHC) is critical, and identifying a predictive biomarker for fibrosis will be helpful for implementing personalized s ... more The case against transfusion‐\transmitted non‐\ABC hepatitis H. J. Alter 2018,Journal of Internal Medicine -Article Click here to view the Original article by Edgren et al. Preferential association of hepatitis C virus with CD19+ B cells is mediated by complement system Richard Y. Wang, Patricia Bare, Valeria De Giorgi, Kentaro Matsuura, Kazi Abdus Salam, Teresa Grandinetti, Cathy Schechterly, Harvey J. Alter 2016,Hepatology -Article Extrahepatic disease manifestations are common in chronic hepatitis C virus (HCV) infection. The mechanism of HCV-related lymphoproliferative disorders is not fully understood. Recent studies have fou ... more Analysis of long noncoding RNA expression in hepatocellular carcinoma of different viral etiology Quan Zhang, Kentaro Matsuura, David E. Kleiner, Fausto Zamboni, Harvey J. Alter , Patrizia Farci 2016,Journal of Translational Medicine -Article BACKGROUND: Dysregulation of long noncoding RNA (lncRNA) expression contributes to the pathogenesis of many human diseases, including liver diseases. Several lncRNAs have been reported to play a role ... more Circulating let‐\7 levels in plasma and extracellular vesicles correlate with hepatic fibrosis progression in chronic hepatitis C Kentaro Matsuura, Valeria De Giorgi, Cathy Schechterly, Richard Y Wang, Patrizia Farci, Yasuhito Tanaka, Harvey J Alter 2016,Hepatology -Article The goal of this study was to determine whether an association exists between circulating microRNA (miRNA) levels and disease progression in chronic hepatitis C (CHC), whether plasma or extracellular ... more A historical perspective on the discovery and elucidation of the hepatitis B virus Timothy M. Block, Harvey J. Alter , W. Thomas London, Mike Bray 2016,Antiviral Research -Article The discovery in 1965 of the Australia antigen, subsequently identified as the hepatitis B virus surface antigen (HBsAg), was such a watershed event in virology that it is often thought to ... more Hepatitis E Virus Does Not Contribute to Hepatic Decompensation Among Patients With Advanced Chronic Hepatitis C Niharika Samala, Elizabeth C. Wright, A. Gretchen Buckler, Vanessa Vargas, Kirti Shetty, K. Rajender Reddy, Michael R. Lucey, Harvey J. Alter, Jay H. Hoofnagle, Marc G. Ghany 2016,Clinical Gastroenterology and Hepatology -Article BACKGROUND AIMS: AbstractText Label=BACKGROUND amp; AIMSHepatitis E (HEV) can cause acute-on-chronic liver failure in persons with pre-existing liver disease. We investi ... more Single-Genome Sequencing of Hepatitis C Virus in Donor-Recipient Pairs Distinguishes Modes and Models of Virus Transmission and Early Diversification Hui Li, Mark B. Stoddard, Shuyi Wang, Elena E. Giorgi, Lily M. Blair, Gerald H. Learn, Beatrice H. Hahn, Harvey J. Alter, Michael P. Busch, Daniel S. Fierer, Ruy M. Ribeiro, Alan S. Perelson, Tanmoy Bhattacharya, George M. Shaw 2016,Journal of Virology -Article Despite the recent development of highly effective anti-hepatitis C virus (HCV) drugs, the global burden of this pathogen remains immense. Control or eradication of HCV will likely require the broad a ... more Inherent transcriptional signatures of NK cells are associated with response to IFNα + rivabirin therapy in patients with Hepatitis C Virus Maria Libera Ascierto, Federica Bozzano, Davide Bedognetti, Francesco Marras, Cathy Schechterly, Kentaro Matsuura, Antonino Picciotto, Simona Marenco, Yingdong Zhao, Valeria DeGiorgi, Michele Sommariva, Lorenzo Moretta, Ena Wang, Harvey J Alter, Francesco M Marincola, Andrea De Maria 2015,Journal of Translational Medicine -Article BACKGROUND: Differences in the expression of Natural Killer cell receptors have been reported to reflect divergent clinical courses in patients with chronic infections or tumors. However, extensive mo ... more An Epidemiologic Investigation of a Case of Acute Hepatitis E Souvik Sarkar, Elenita M. Rivera, Ronald E. Engle, Hanh T. Nguyen, Cathy A. Schechterly, Harvey J. Alter, T. Jake Liang, Robert H. Purcell, Jay H. Hoofnagle, Marc G. Ghany 2015,Journal of Clinical Microbiology -Article Hepatitis E virus (HEV) is considered a zoonotic infection in developed nations. A case of acute hepatitis E in a researcher following a scalpel injury while working on a pig prompted a seroepidemiolo ... more Immunoglobulin with High-Titer In Vitro Cross-Neutralizing Hepatitis C Virus Antibodies Passively Protects Chimpanzees from Homologous, but Not Heterologous, Challenge Jens Bukh, Ronald E. Engle, Kristina Faulk, Richard Y. Wang, Patrizia Farci, Harvey J. Alter, Robert H. Purcell 2015,Journal of Virology -Article The importance of neutralizing antibodies (NAbs) in protection against hepatitis C virus (HCV) remains controversial. We infused a chimpanzee with H06 immunoglobulin from a genotype 1a HCV-infected pa ... more Transfusion‐\associated hepatitis before the screening of blood for hepatitis risk factors Ronald E. Engle, Jens Bukh, Harvey J. Alter, Suzanne U. Emerson, Joni L. Trenbeath, Hanh T. Nguyen, Alicia Brockington, Tanaji Mitra, Robert H. Purcell 2014,Transfusion -Article BACKGROUND: The true incidence of transfusion-associated hepatitis (TAH) before blood screening is unknown. Our aims were to reevaluate blood recipients receiving unscreened blood and analyze hepatiti ... more Differential Responses of Plasmacytoid Dendritic Cells to Influenza Virus and Distinct Viral Pathogens Jaime M. Thomas, Zoltan Pos, Jennifer Reinboth, Richard Y. Wang, Ena Wang, Gregory M. Frank, Paolo Lusso, Giorgio Trinchieri, Harvey J. Alter, Francesco M. Marincola, Emmanuel Thomas 2014,Journal of Virology -Article Plasmacytoid dendritic cells (pDCs) are key components of the innate immune response that are capable of synthesizing and rapidly releasing vast amounts of type I interferons (IFNs), particularly IFN- ... more The road not taken or how I learned to love the liver: A personal perspective on hepatitis history Harvey J. Alter 2014,Hepatology -Article Corrigendum to “The modulation of hepatitis C virus 1a replication by PKR is dependent on NF-kB mediated interferon beta response in Huh7.5.1 cells” Lumin Zhang, Harvey J. Alter, Haiping Wang, Shuaizheng Jia, Ena Wang, Francesco M. Marincola, James W.-K. Shih, Richard Y. Wang 2013,Virology -Article Association of IL28B genotype with fibrosis progression and clinical outcomes in patients with chronic hepatitis C: A longitudinal analysis Mazen Noureddin, Elizabeth C. Wright, Harvey J. Alter, Shauna Clark, Emmanuel Thomas, Richard Chen, Xiongce Zhao, Cathy Conry‐\Cantilena, David E. Kleiner, T. Jake Liang, Marc G. Ghany 2013,Hepatology -Article Interleukin (IL)28B polymorphisms are associated with spontaneous clearance of hepatitis C virus (HCV) infection and response to therapy. Whether IL28B genotype affects fibrosis progression or clinica ... more An assessment of hepatitis E virus (HEV) in US blood donors and recipients: no detectable HEV RNA in 1939 donors tested and no evidence for HEV transmission to 362 prospectively followed recipients Chenyu Xu, Richard Y. Wang, Cathy A. Schechterly, Shengxiang Ge, James W. Shih, Ning‐\Shao Xia, Naomi L.C. Luban, Harvey J. Alter 2013,Transfusion -Article BACKGROUND: Hepatitis E virus (HEV) infection has become relevant to blood transfusion practice because isolated cases of blood transmission have been reported and because HEV has been found to cause ... more Blood system changes since recognition of transfusion‐\associated AIDS Jay S. Epstein, Harold W. Jaffe, Harvey J. Alter, Harvey G. Klein 2013,Transfusion -Article Evolutionary analysis of hepatitis C virus gene sequences from 1953 Rebecca R. Gray, Yasuhito Tanaka, Yutaka Takebe, Gkikas Magiorkinis, Zelma Buskell, Leonard Seeff, Harvey J. Alter, Oliver G. Pybus 2013,Philosophical Transactions of the Royal Society B Biological Sciences -Article Reconstructing the transmission history of infectious diseases in the absence of medical or epidemiological records often relies on the evolutionary analysis of pathogen genetic sequences. The precisi ... more G105 Profibrogenic Chemokines and Viral Evolution Predict Rapid Progression of Hepatitis C to Cirrhosis Patrizia Farci, Harvey J. Alter 2013,JAIDS Journal of Acquired Immune Deficiency Syndromes -Article The clinical presentation and outcomes of chronic hepatitis C are highly variable, and it is not possible to predict which individuals will rapidly evolve to severe fibrosis and liver failure. Using s ... more The modulation of hepatitis C virus 1a replication by PKR is dependent on NF-kB mediated interferon beta response in Huh7.5.1 cells Lumin Zhang, Harvey J. Alter, Haiping Wang, Shuaizheng Jia, Ena Wang, Francesco M. Marincola, James W.-K. Shih, Richard Y. Wang 2013,Virology -Article Protein kinase R (PKR), a sensor of double-stranded RNA, plays an important role in the host response to viral infection. Hepatitis C genotype 2a virus (HCV2a) has been shown to induce PKR activation ... more Isolation of Human Monoclonal Antibodies to the Envelope E2 Protein of Hepatitis C Virus and Their Characterization Yohko K. Shimizu, Minako Hijikata, Masamichi Oshima, Kazufumi Shimizu, Harvey J. Alter, Robert H. Purcell, Hiroshi Yoshikura, Hak Hotta 2013,PLoS ONE -Article We isolated and characterized two human monoclonal antibodies to the envelope E2 protein of hepatitis C virus (HCV). Lymphoblastoid cell lines stably producing antibodies were obtained by immortalizin ... more Investigation of residual hepatitis C virus in presumed recovered subjects Kei Fujiwara, Robert D. Allison, Richard Y. Wang, Patricia Bare, Kentaro Matsuura, Cathy Schechterly, Krishna Murthy, Francesco M. Marincola, Harvey J. Alter 2013,Hepatology -Article Recent studies have found hepatitis C virus (HCV) RNA in peripheral blood mononuclear cells (PBMCs) of the majority of presumed recovered subjects. We investigated this unexpected finding using sample ... more A Multicenter Blinded Analysis Indicates No Association between Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and either Xenotropic Murine Leukemia Virus-Related Virus or Polytropic Murine Leukemia Virus Harvey J. Alter, Judy A. Mikovits, William M. Switzer, Francis W. Ruscetti, Shyh-Ching Lo, Nancy Klimas, Anthony L. Komaroff, Jose G. Montoya, Lucinda Bateman, Susan Levine, Daniel Peterson, Bruce Levin, Maureen R. Hanson, Afia Genfi, Meera Bhat, HaoQiang Zheng, Richard Wang, Bingjie Li, Guo-Chiuan Hung, Li Ling Lee, Stephen Sameroff, Walid Heneine, John Coffin, Mady Hornig, W. Ian Lipkin 2012,mBio -Article The disabling disorder known as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) has been linked in two independent studies to infection with xenotropic murine leukemia virus-related vir ... more To have B or not to have B: Vaccine and the potential eradication of hepatitis B Harvey J. Alter 2012,Journal of Hepatology -Article Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis Patrizia Farci, Kurt Wollenberg, Giacomo Diaz, Ronald E. Engle, Maria Eliana Lai, Paul Klenerman, Robert H. Purcell, Oliver G. Pybus, Harvey J. Alter 2012,Proceedings of the National Academy of Sciences of the United States of America -Article Chronic hepatitis C may follow a mild and stable disease course or progress rapidly to cirrhosis and liver-related death. The mechanisms underlying the different rates of disease progression are unkno ... more A 25-Year Study of the Clinical and Histologic Outcomes of Hepatitis C Virus Infection and Its Modes of Transmission in a Cohort of Initially Asymptomatic Blood Donors Robert D. Allison, Cathy Conry-Cantilena, Deloris Koziol, Cathy Schechterly, Paul Ness, Joan Gibble, David E. Kleiner, Marc G. Ghany, Harvey J. Alter 2012,The Journal of Infectious Diseases -Article BACKGROUND: A total of 738 volunteer blood donors who were positive for anti-hepatitis C virus (HCV) were assessed for risk factors and outcomes for up to 15 years within the study and up to 54 years ... more The clinical relevance of persistent recombinant immunoblot assay–indeterminate reactions: insights into the natural history of hepatitis C virus infection and implications for donor counseling Addisalem T. Makuria, Sukanya Raghuraman, Peter D. Burbelo, Cathy C. Cantilena, Robert D. Allison, Joan Gibble, Barbara Rehermann, Harvey J. Alter 2012,Transfusion -Article BACKGROUND: Recombinant immunoblot assay (RIBA) is used to determine the specificity of antibody to hepatitis C virus (anti-HCV). The RIBA result is recorded as positive, negative, or indeterminate. T ... more Infectivity in chimpanzees (Pan troglodytes) of plasma collected before HCV RNA detectability by FDA-licensed assays: implications for transfusion safety and HCV infection outcomes Michael P. Busch, Krishna K. Murthy, Steven H. Kleinman, Dale F. Hirschkorn, Belinda L. Herring, Eric L. Delwart, Vito Racanelli, Joo Chun Yoon, Barbara Rehermann, Harvey J. Alter 2012,Blood -Article Serial plasma aliquots (50 mL) obtained from 10 commercial donors who converted from hepatitis C virus (HCV) RNA negative to positive were transfused into 2 chimpanzees to assess infectivity during ea ... more Absence of transfusion‐\associated microchimerism in pediatric and adult recipients of leukoreduced and gamma‐\irradiated blood components Rosa Sanchez, Tzong‐\Hae Lee, Li Wen, Leilani Montalvo, Cathy Schechterly, Camilla Colvin, Harvey J. Alter, Naomi L.C. Luban, Michael P. Busch 2012,Transfusion -Article BACKGROUND: Transfusion-associated microchimerism (TA-MC), the persistence of significant levels of donor white blood cells (WBCs) in blood recipients for prolonged periods, has been demonstrated afte ... more A2 Molecular Evolution of Hepatitis C Virus (HCV) and Clinical Outcome in Patients With Hepatitis C Patrizia Farci, Kurt Wollenberg, Harvey J. Alter 2012,JAIDS Journal of Acquired Immune Deficiency Syndromes -Article HCV causes persistent infection in up to 85% of infected individuals, and about 30% of them develop long-term sequelae, such as cirrhosis or hepatocellular carcinoma. The mechanisms of viral persisten ... more Hepatitis C: the end of the beginning and possibly the beginning of the end. Harvey J Alter, T Jake Liang 2012,Annals of Internal Medicine -Article Retraction for Lo et al., Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors Shyh-Ching Lo, Natalia Pripuzova, Bingjie Li, Anthony L Komaroff, Guo-Chiuan Hung, Richard Wang, Harvey J Alter 2012,Proceedings of the National Academy of Sciences of the United States of America -Article Failure to Confirm XMRV/MLVs in the Blood of Patients with Chronic Fatigue Syndrome: A Multi-Laboratory Study Graham Simmons, Simone A. Glynn, Anthony L. Komaroff, Judy A. Mikovits, Leslie H. Tobler, John Hackett, Ning Tang, William M. Switzer, Walid Heneine, Indira K. Hewlett, Jiangqin Zhao, Shyh-Ching Lo, Harvey J. Alter, Jeffrey M. Linnen, Kui Gao, John M. Coffin, Mary F. Kearney, Francis W. Ruscetti, Max A. Pfost, James Bethel, Steven Kleinman, Jerry A. Holmberg, Michael P. Busch, for the Blood XMRV Scientific Research Working Group 2011,Science -Article Murine leukemia viruses (MLVs), including xenotropic-MLV-related virus (XMRV), have been controversially linked to chronic fatigue syndrome (CFS). To explore this issue in greater depth, we compiled c ... more The natural history of acute hepatitis C: clinical presentation, laboratory findings and treatment outcomes R. Loomba, M. M. Rivera, R. McBurney, Y. Park, V. Haynes‐\Williams, B. Rehermann, H. J. Alter, S. K. Herrine, T. J. Liang, J. H. Hoofnagle, T. Heller 2011,Alimentary Pharmacology Therapeutics -Article BACKGROUND: Acute hepatitis C has variable modes of presentation and frequently results in chronic infection. Its optimal management has yet to be defined. AIM: To establish natural history and compli ... more Reply to Erlwein et al. and Martin: On detection of murine leukemia virus-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors Shyh-Ching Lo, Natalia Pripuzova, Bingjie Li, Anthony L. Komaroff, Guo-Chiuan Hung, Richard Wang, Harvey J. Alter 2010,Proceedings of the National Academy of Sciences of the United States of America -Article Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors Shyh-Ching Lo, Natalia Pripuzova, Bingjie Li, Anthony L. Komaroff, Guo-Chiuan Hung, Richard Wang, Harvey J. Alter 2010,Proceedings of the National Academy of Sciences of the United States of America -Article Chronic fatigue syndrome (CFS) is a serious systemic illness of unknown cause. A recent study identified DNA from a xenotropic murine leukemia virus-related virus (XMRV) in peripheral blood mononuclea ... more Parvovirus B19 infection transmitted by transfusion of red blood cells confirmed by molecular analysis of linked donor and recipient samples Mei‐\ying W. Yu, Harvey J. Alter, Maria Luisa A. Virata‐\Theimer, Yansheng Geng, Li Ma, Cathy A. Schechterly, Camilla A. Colvin, Naomi L.C. Luban 2010,Transfusion -Article BACKGROUND: Extremely high viremic levels of parvovirus B19 (B19V) can be found in acutely infected, but asymptomatic donors. However, reports of transmission by single-donor blood components are rare ... more Understanding the natural history of chronic HBV and HCV infections. David L Thomas, Adrian M Di Bisceglie, Harvey J Alter, Norah A Terrault 2010,The Journal of Family Practice -Article Genomic scale analysis of racial impact on response to IFN-α Zoltan Pos, Silvia Selleri, Tara L. Spivey, Jeanne K. Wang, Hui Liu, Andrea Worschech, Marianna Sabatino, Alessandro Monaco, Susan F. Leitman, Andras Falus, Ena Wang, Harvey J. Alter, Francesco M. Marincola 2010,Proceedings of the National Academy of Sciences of the United States of America -Article Limited responsiveness to IFN-alpha in hepatitis C virus (HCV)-infected African-Americans compared to European Americans (AAs vs. EAs) hinders the management of HCV. Here, we studied healthy non-HCV-i ... more
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