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; AIMS">Hepatitis 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” [Virology 438 (2013) 28–36]

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