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  • Publications | DahariLab

    Publications 2025 January 2025 HBV serum RNA kinetics during nucleic acid polymers based therapy predict functional cure Hershkovich, L., et al. Full Text PUBMED January 2025 Modeling of randomized hepatitis C vaccine trials: bridging the gap between controlled human infection models and real-word testing Mackesy-Amiti et al. Full Text PUBMED February 2025 Modeling challenges of hepatitis D virus kinetics during bulevirtide-based therapy Mhlanga, A., et al. Full Text PUBMED February 2025- preprint Modeling of hepatitis B virus infection spread in primary human hepatocytes Shi Z, et al. Preprint 2024 December 2024 Theoretical modeling of hepatitis C acute infection in liver-humanized mice support pre-clinical assessment of candidate viruses for controlled-human-infection studies Shi Z, et al. Full Text PUBMED December 2024 Modelling of hepatitis B virus kinetics and accumulation of cccDNA in primary human hepatocytes Shekhtman, L., et al. Full Text September 2024 Commentary on: Bulevirtide Combined with Pegylated Interferon for Chronic Hepatitis D Dahari, H., Cotler, SJ. Full Text August 2024 Interferon alpha induces a stronger antiviral effect than interferon lambda in HBV/HDV infected humanized mice Duehren, S., et al. Full Text PUBMED July 2024 Spatial inequities in access to medications for treatment of opioid use disorder highlight scarcity of methadone providers under counterfactual scenarios Tatara, E., et al. Full Text PUBMED April 2024 Mathematical Models of Early Hepatitis B Virus Dynamics in Humanized Mice Ciupe, S., et al. Full Text PUBMED March 2024 Reducing Sample Size While Improving Equity in Vaccine Clinical Trials: A Machine Learning-Based Recruitment Methodology with Application to Improving Trials of Hepatitis C Virus Vaccines in People Who Inject Drugs Chiu, R., et al. Full Text PUBMED February 2024 Advances and Challenges in Managing Hepatitis D Virus: Evolving Strategies Gopalakrishna, H., et al. Full Text PUBMED February 2024 Modelling HDV kinetics under entry-inhibitor Bulevirtide suggests the existence of two HDV-infected cell populations Shekhtman, L., et al. Full Text PUBMED 2023 October 2023 Hepatitis D Virus and HBsAg Dynamics in the era of new Antiviral Treatments Shekhtman, L., et al. Full Text PUBMED July 2023 Modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis B virus infection kinetics Hailegiorgis, A., et al. Full Text PUBMED July 2023 Herpes Simplex Virus, Human Papillomavirus, and Cervical Cancer: Overview, Relationship, and Treatment Implications Sausen D., et al. Full Text June 2023 Hepatitis delta virus RNA decline post inoculation in human NTCP transgenic mice is biphasic Maya S., et al. Full Text PUBMED June 2023 Treatment of Chronic Hepatitis D with Peginterferon Lambda - The Phase 2 LIMT-1 Clinical Trial Etzion O., et al. Full Text PUBMED April 2023 Rapid monophasic hepatitis B surface antigen decline during nucleic-acid polymers-based therapy predicts functional cure Hershkovich, L., et al. Full Text PUBMED January 2023 Modeling-Based Response-Guided Hepatitis C Treatment during Pregnancy and Postpartum Kushner, T., et al. Full Text PUBMED 2022 December 2022 Hepatitis B and Hepatitis D Viruses: A Comprehensive Update with an Immunological Focus Sausen D., et al. Full Text PUBMED November 2022 Epstein–Barr Virus (EBV) Epithelial Associated Malignancies: Exploring Pathologies and Current Treatments Shechter O., et al. Full Text PUBMED October 2022 Modeling the Interplay between HDV and HBV in Chronic HDV/HBV Patients Mhlanga A., et al. Full Text PUBMED June 2022 Advances in Parameter Estimation and Learning from Data for Mathematical Models of Hepatitis C Viral Kinetics Reinharz V., et al. Full Text PUBMED March 2022 Modeling-based response-guided DAA therapy for chronic hepatitis C to identify individuals for shortening treatment duration Goyal A., et al. Full Text PUBMED March 2022 Modeling hepatitis C micro-elimination among people who inject drugs with direct-acting antivirals in metropolitan Chicago Tatara E., et al. Full Text PUBMED January 2022 Mathematical modeling suggests that entry-inhibitor Bulevirtide may interfere with hepatitis D virus clearance from circulation Shekhtman L., et al. Full Text PUBMED January 2022 Machine learning for mathematical models of HCV kinetics during antiviral therapy Churkin A., et al. Full Text PUBMED January 2022 A meta-analysis of 20 years of data on people who inject drugs in metropolitan Chicago to inform computational modeling Boodram B., et al. Full Text PUBMED 2021 December 2021 A Mathematical Model for early HBV and -HDV Kinetics during Anti-HDV Treatment Zakh R., et al. Full Text PUBMED November 2021 Modeling hepatitis C virus kinetics during liver transplantation reveals the role of the liver in virus clearance Shekhtman L., et al. Full Text PUBMED September 2021 Ginkgolic acid inhibits Coronavirus strain 229E infection of human epithelial lung cells Bhutta M. S., et al Full Text PUBMED September 2021 Stress-Induced Epstein-Barr Virus Reactivation Sausen D. G., et al Full Text PUBMED September 2021 Letter to the Editor: Examining HBV RNA kinetics during NA treatment - are NA multifunctional antiviral agents? Dahari H., et al Full Text PUBMED August 2021 A Mathematical Analysis of HDV Genotypes: From Molecules to Cells Zakh R., et al. Full Text PUBMED July 2021 Advances and Challenges in Managing Hepatitis D Virus: Evolving Strategies Durso-Cain, K., et al. Full Text PUBMED April 2021 Understanding hepatitis B virus dynamics and the antiviral effect of interferon-a treatment in humanized chimeric mice Reinharz V., et al. Full Text PUBMED January 2021 Early HBV RNA kinetics under NA treatment may reveal new insights into HBV RNA dynamics and NA mode of action-more detailed kinetic studies are needed Dahari H., et al. Full Text PUBMED January 2021 Understanding the antiviral effects of RNAi-based therapy on chronic hepatitis B infection Kadelka S., et al. Full Text PUBMED 2020 October Response guided therapy for reducing duration of direct acting antivirals in chronic hepatitis C infected patients: a Pilot study Etzion O., et al. Full Text PUBMED August Efficient Methods for Parameter Estimation of Ordinary and Partial Differential Equation Models of Viral Hepatitis Kinetics Churkin A., et al. Full Text PUBMED July HCVMultiscaleFit: A Simulator for Parameter Estimation in Multiscale Models of Hepatitis C Virus Dynamics Churkin A., et al. Full Text PUBMED June Modeling based response guided therapy in subjects with recent hepatitis C infection Gorstein E., et al. Full Text PUBMED May Evaluation of short-course direct-acting antivirals and ezetimibe to prevent HCV infection in recipients of organs from HCV-infected donors: A single-centre, open-label study Feld J.J., et al. Full Text PUBMED April Modelling hepatitis D virus RNA and HBsAg dynamics during nucleic acid polymer monotherapy suggest rapid turnover of HBsAg Shekhtman L, et al. Full Text PUBMED April Modeling-based response-guided therapy for chronic hepatitis C under glecaprevir/pibrentasvir may identify patients for ultra-short treatment duration Dasgupta S, et al. Full Text PUBMED April Sustained Virological Response Following an 11 Day Course of Direct Acting Antiviral Therapy for Hepatitis C Infection Yardeni D, et al. Full Text PUBMED January Modeling Challenges of Ebola Virus -Host Dynamics during Infection and Treatment Chertow D.S., et al. Full Text PUBMED 2019 July A Parameter Estimation Method for Multiscale Models of Hepatitis C Virus Dynamics Reinharz V, et al. Full Text PUBMED July Plasma hepatitis E virus kinetics in solid organ transplant patients receiving ribavirin Lhomme S, et al. Full Text PUBMED June Multi-objective model exploration of hepatitis C elimination in an agent-based model of people who inject drugs Tatara E, et al. Full Text PUBMED May Early HCV viral kinetics under DAAs may optimize duration of therapy in patients with compensated cirrhosis Gambato M, et al. Full Text PUBMED April Modeling indicates efficient vaccine-based interventions for the elimination of hepatitis C virus among persons who inject drugs in metropolitan Chicago Echevarria D, et al. Full Text PUBMED March Early Multiphasic HBV Infection Initiation Kinetics Is Not Clone-Specific and Is Not Affected by Hepatitis D Virus (HDV) Infection Tsuge M, et al. Full Text PUBMED March A randomized, proof-of-concept clinical trial on repurposing chlorcyclizine for the treatment of chronic hepatitis C Koh C, et al. Full Text PUBMED January Modeling suggests that microliter volumes of contaminated blood caused an outbreak of hepatitis C during computerized tomography Shteyer E, et al. Full Text PUBMED 2018 August Acute hepatitis B virus infection in humanized chimeric mice has multiphasic viral kinetics Ishida Y, et al. Full Text PUBMED July Modeling of patient virus titers suggests that availability of a vaccine could reduce hepatitis C virus transmission among injecting drug users Major M, et al. Full Text PUBMED June Numerical schemes for solving and optimizing multiscale models with age of hepatitis C virus dynamics Reinharz V, et al. Full Text PUBMED April Accounting for Space--Quantification of Cell-to-Cell Transmission Kinetics Using Virus Dynamics Models Kumberger P, et al. Full Text PUBMED February How to eliminate HCV in people who inject drugs in the USA Dahari H, et al. PUBMED February High-Risk Geographic Mobility Patterns among Young Urban and Suburban Persons who Inject Drugs and their Injection Networks Members Boodram B, et al. PUBMED 2017 December HCV kinetic and modeling analyses project shorter durations to cure under combined therapy with daclatasvir and asunaprevir in chronic HCV-infected patients Canini L et al. PUBMED October A Robust and Efficient Numerical Method for RNA-Mediated Viral Dynamics Reinharz V, et al. PUBMED August Modeling HCV cure after an ultra-short duration of therapy with direct acting agents Goyal A, et al. PUBMED June Pharmacokinetics and pharmacodynamics modeling of lonafarnib in patients with chronic hepatitis delta virus infection Canini L, et al. PUBMED May End of treatment RNA-positive/sustained viral response in an individual with acute HCV infection treated with direct-acting antivirals Shtyer E, et al. PUBMED January Prevalence of End of Treatment RNA-Positivity/Sustained Viral Response in HCV Patients Treated with Sofosbuvir Combination Therapies Malespin M, et al. PUBMED 2016 June HCV Kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir Dahari H, et al. PUBMED September HCV dynamics and cellular gene expression in uPA-SCID chimeric mice with humanized livers during intravenous silibinin monotherapy DebRoy S, et al. PUBMED July Hepatitis C virus cure after direct acting antiviral-related drug-induced liver injury: Case report Hasin Y, et al. PUBMED September Resurrection of response-guided therapy for sofosbuvir combination therapies Dahari H, et al. PUBMED September Cure prevents more than HCV transmission Dahari H, et al PUBMED 2014 December Understanding early serum hepatitis D virus and HBsAg kinetics during pegylated interferon-alfa therapy via mathematical modeling Guedj J, et al. PUBMED check Treatment of hepatitis C with an interferon-based lead-in phase: A perspective from mathematical modeling Rong L, et al. PUBMED January Effect of Ribavirin on Viral Kinetics and Liver Gene Expression in Chronic Hepatitis C Rotman Y, et al. PUBMED June Individualized treatment for patients with low HCV load (genotype 1): A viral kinetic approach. Dahari H, et al. PUBMED 2013 March Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a new estimate of the hepatitis C virus half-life check PUBMED April Modeling the acute and chronic phases of Theiler murine encephalomyelitis virus infection Zhang J, et al. PUBMED August check Gutfraind A, et al. PUBMED March Multiscale modeling approach predicts that the protease inhibitor danoprevir blocks several distinct stages of the HCV replication in vivo. check PUBMED July The HCV NS5A inhibitor daclatasvir has dual mode of action and reveals a shorter HCV half-life estimate. Guedj J, et al. PUBMED check Silymarin for HCV infection. Polyak SJ, et al. PUBMED January Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy Canini L, et al. PUBMED 2015 October Oral Prenylation Inhibition with Lonafarnib in Chronic Hepatitis D Infection: a randomized, double-blinded, placebo controlled phase 2a trial Koh C, et al. PUBMED September Agent-based model forecasts aging of the population of people who inject drugs in metropolitan Chicago and changing prevalence of hepatitis C infections Gutfraind A, et al. PUBMED August Mathematical modeling of hepatitis C prevalence reduction with antiviral treatment scale-up in persons who inject drugs in metropolitan Chicago Echevarria D, et al. PUBMED July Quantification of HCV cell-to-cell spread using a stochastic modeling approach Graw F, et al. PUBMED June Effect of interferon-alfa therapy on hepatitis D virus Guedj J, et al. PUBMED February Sustained virological response with intravenous silibinin: individualized IFN-free therapy via real-time modeling of HCV kinetics Dahari H, et al. PUBMED January Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy Canini L, et al. PUBMED 2012 May Understanding silibinin's modes of action against HCV using viral kinetic modeling Guedj J, Dahari H, et al. PUBMED April Hepatitis C viral kinetics with the nucleoside polymerase inhibitor mericitabine (RG7128) Guedj J, et al. PUBMED 2011 March Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a new estimate of the hepatitis C virus half-life check PUBMED April Modeling the acute and chronic phases of Theiler murine encephalomyelitis virus infection Zhang J, et al. PUBMED August check Gutfraind A, et al. PUBMED March Multiscale modeling approach predicts that the protease inhibitor danoprevir blocks several distinct stages of the HCV replication in vivo. check PUBMED July The HCV NS5A inhibitor daclatasvir has dual mode of action and reveals a shorter HCV half-life estimate. Guedj J, et al. PUBMED March Hepatocyte proliferation and hepatitis C virus (HCV) kinetics. Dahari H, et al. PUBMED 2010 May Rapid emergence of hepatitis C virus protease inhibitor resistance. L. Rong, et al. PUBMED September Quantitative evaluation of HCV vaccine success: a meta-analysis. Dahari H, et al. PUBMED May Pharmacodynamics of PEG-IFN alpha-2a in HIV/HCV co-infected patients: Implications for treatment outcomes. Dahari H, et al. PUBMED August The rate of hepatitis C virus infection initiation in vitro is directly related to particle density Ali Sabahi, et al. PUBMED March Thiazole antibiotics against breast cancer. Marianna Halasi, et al. PUBMED September Novel mechanism of antibodies to hepatitis B virus in blocking viral particle release from cells. Neumann AU, et al. PUBMED August A perspective on modeling hepatitis C virus infection. Guedj J, et al. PUBMED 2009 July Modeling subgenomic HCV RNA kinetics during interferon-a treatment. Dahari H, et al. PUBMED August Mathematical modeling of viral kinetics under immune control during primary HIV-1 infection. Burg D, et al. PUBMED . Modeling HCV kinetics: The relationship between the infected cell loss rate and the final slope of viral decay. Dahari H, et al. PUBMED April A mathematical model of hepatitis C virus dynamics in patients with high baseline viral loads or advanced liver disease. Dahari H, et al. PUBMED January Modeling complex decay profiles of hepatitis B virus during antiviral therapy. Dahari H, et al. PUBMED . Mathematical modeling of HCV infection and treatment. HCV infection. Dahari H, et al. PUBMED January Analysis of hepatitis C virus infection models with hepatocyte homeostasis. Reluga T , et al. PUBMED April Hepatitis B virus clearance rate estimates. Dahari H, et al. PUBMED 2008 Hepatitis C viral kinetics in special populations Dahari H, et al. PUBMED 2007 July Triphasic decline of HCV RNA during antiviral therapy. Dahari H, et al PUBMED July Modeling HCV Dynamics: Liver regeneration and critical drug efficacy. Dahari H, et al PUBMED July Early ribavirin pharmacokinetics, HCV RNA and alanine aminotransferase kinetics in HIV/HCV co-infected patients during treatment with pegylated Interferon and ribavirin. Dahari H, et al PUBMED January Mathematical modeling of subgenomic hepatitis C viral replication in Huh-7 cells. Dahari H, et al PUBMED June Hepatitis C virus RNA kinetics: Drug efficacy and the rate of HCV-infected cells loss. Dahari H, Perelson AS, et al. PUBMED October Hepatitis C virus kinetics in chimeric mice during antiviral therapy. Dahari H, Perelson AS, et al. PUBMED 2006 October The extrahepatic contribution to HCV plasma viremia. Dahari H, et al. PUBMED 2005 Mathematical Modeling of Primary Hepatitis C Infection: Non-cytolytic clearance and early blockage of virion production. Dahari H, et al. PUBMED Second Hepatitis C Compartment Indicated by Viral Dynamics during Liver Transplantation. Dahari H, et al. PUBMED 2004 Hepatitis C Virus Kinetics and Host Responses Associated with Disease and Outcome of Infection. Major ME, et al. PUBMED Antiviral Action of Ribavirin in Chronic Hepatitis C. Pawlotsky JM, et al. PUBMED 2002 October Clinical utility of total HCV core antigen quantification: a new indirect marker of HCV replication. Bouvier-Alias M, et al. PUBMED 2000 July Differences in viral dynamics between genotypes 1 and 2 of hepatitis C virus. Neumann AU, et al. PUBMED 1998 July Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Neumann AU, et al. PUBMED

  • Home | DahariLab

    Dahari Lab Mathematical/Computational Virology & Medicine Theoretical foundations advancing basic science and patient-focused applications Dahari Lab specializes in the study of viral infection dynamics, antiviral treatment responses, and vaccine efficacy. Our scientific inquiry focuses on hepatitis viruses—HCV, HBV, HDV, and HEV—integrating experimental and clinical research with theoretical modeling. We aim to deepen the understanding of viral transmission and inform public health strategies. Learn About Our Research... Featured Publications Modelling of hepatitis B virus kinetics and accumulation of cccDNA in primary human hepatocytes December 2024 Our Current Research Focus HBV HDV HCV Other viruses Q&A with Dr. Dahari LIGHTS SHOP Highlights Presentation: Can we stop Bulevirtide? Lessons learned from viral kinetics modelling Dr. Dahari [OCT 2024] Presentation: Bridging the gap between controlled human infection models and real-word testing using computational modeling of randomized hepatitis C vaccine trials. Dr. Major [SEPT 2024] What happens to HCV incidence after WHO elimination goal is met? Agent-based modeling predicts sustained availability of direct-acting antivirals among people who inject drugs is required to prevent returning to pre-elimination levels. Dr. Dahari [JUNE 2024] Presentation: Modeling HDV Kinetics in the Era of Novel Antivirals. Dr. Dahari [JAN 2024] White House: A U.S. plan for HCV elimination Advancements to Optimize DAA Treatment in HCV Patients Interview with Harel Dahari & Ohad Etzion HCV research (2004-2007) with Dr. Charles Rice, 2020 Nobel Prize recipient. Dahari Lab believes that a diverse community of students, faculty, trainees, and staff promotes innovative research, increases quality of patient care, and provides the richest set of viewpoints for solving complex problems. Location Our Commitment to Diversity

  • Conference | DahariLab

    DeltaCure, 3rd International Meeting 75th Annual Meeting of the American Association for the study of Liver Diseases Nov 15-19, 2024 San Diego, CA, USA Leeor Hershkovich, Harel Dahari, Scott J. Cotler, Theo Heller, Chris Koh, Jeffrey Glenn, Tarik Asselah, Saeed Hamid, Ohad Etzion. Characterization of HDV RNA and HBsAg during pegylated interferon-alpha and ritonavir-boosted lonafarnib combination therapy: The D-LIVR study. Hepatology 2024 Vol 80(Suppl. 1):S312 (Poster of Distinction) Ori Wasserman, Louis Shekhtman, Scott J. Cotler, Elisabetta Degasperi, Maria Paola Anolli, Sara Colonia Uceda Renteria, Dana Sambarino, Marta Borghi, Riccardo Perbellini, Floriana Facchetti, Ferruccio Ceriotti, Harel Dahari, Pietro Lampertico. Bulevirtide monotherapy in patients with compensated cirrhosis and CSPH: a 96-week interim kinetic analysis of real-life setting. Hepatology 2024 accepted Vol 80(Suppl. 1):S309-S310 Ashish, Goyal, Yuji Ishida, Hiromi Abe-Chayama, Ophir Dahari, Chise Tateno-Mukaidani, Harel Dahari, Kazuaki Chayama. Mathematical modeling of acute HBV infection in humanized mice treated with HBs antibodies. Hepatology 2024 Vol 80(Suppl. 1):S335-S336 Mary-Ellen Mackesy-Amiti, Alexander Gutfraind, Eric Tatara, Nicholson T. Collier, Scott J. Cotler, Kimberly Page, Jonathan Ozik, Basmattee Boodram, Marian Major, Harel Dahari. Bridging the gap between controlled human infection models and real-word testing using computational modeling of randomized hepatitis C vaccine trials. Hepatology 2024 Vol 80(Suppl. 1):S405 DeltaCure, 3rd International Meeting Oct 11-12, 2024 Milan, Italy Ori Wasserman, Louis Shekhtman, Scott J. Cotler, Elisabetta Degasperi, Maria Paola Anolli, Sara Colonia Uceda Renteria, Dana Sambarino, Marta Borghi, Riccardo Perbellini, Floriana Facchetti, Ferruccio Ceriotti, Harel Dahari, Pietro Lampertico. Bulevirtide monotherapy in patients with compensated cirrhosis and CSPH: a 96-week interim kinetic analysis of real-life setting. 30th International Symposium on HCV, Flaviviruses and related Viruses Sept 25-28, 2024 Oxford, UK Eric Tatara, Louis Shekhtman, Nicholson Collier, Marian Major, Mary Ellen Mackesy-Amiti, Jonathan Ozik, Basmattee Boodram, Harel Dahari. What happens to HCV incidence after WHO elimination goal is met using direct-acting antivirals? Agent-based modeling emphasizes the need for vaccines to prevent returning to pre-elimination levels in people who inject drugs. Mary-Ellen Mackesy-Amiti, Alexander Gutfraind, Eric Tatara, Nicholson T. Collier, Scott J. Cotler, Kimberly Page, Jonathan Ozik, Basmattee Boodram, Marian Major, Harel Dahari. Bridging the gap between controlled human infection models and real-word testing using computational modeling of randomized hepatitis C vaccine trials. (Oral talk) HBV International Meeting Sept 11-15, 2024 Chicago, IL, USA Oxford, UK Adquate Mhlanga, E. Fabian Cardozo-Ojeda, Sarah Duehren, Scott J. Cotler, Saeed S. Hamid, Yoav Lurie, Edward Gane, Anat Nevo-Shor, David Yardeni, Jeffrey Glenn, Harel Dahari, Ohad Etzion. Mathematical modeling of HDV RNA, ALT and HBsAg kinetics suggests a dual mode of action of peginterferon lambda: The LIMT-1 Study. Adquate Mhlanga, Rami Zakh, Sarah Duehren, Alexander Churkin, Vladimir Reinharz, Danny Barash, Jeffrey Glenn, Ohad Etzion, Scott J. Cotler, Cihan Yurdaydin, Harel Dahari Understanding the interplay between HDV RNA, HBV DNA and HBsAg during lonafarnib-based therapy via mathematical modeling: The LOWR HDV-1 Study. Zhenzhen Shi, Masataka Tsuge, Takuro Uchida, Yuji Teraoka, Nicholson T. Collier, Susan Uprichard, Jonathan Ozik, Yuji Ishida, Chise Tateno, Harel Dahari, Kazuaki Chayama. Modeling infection kinetics in primary human hepatocytes reveals quantitative insight into HBV production cycle and spread. Louis Shekhtman, Yuji Ishida, Masataka Tsuge, Vladimir Reinharz, Chise Tateno-Mukaidani, Susan L Uprichard, Harel Dahari, Kazuaki Chayama. Modeling of hepatitis B virus kinetics and accumulation of cccDNA in primary human hepatocytes. The International Liver Congress, 59th annual meeting of the European Association for the Study of the Liver (EASL) June 5-8, 2024 Milan, Italy Leeor Hershkovich, Harel Dahari, Scott J. Cotler, Ingrid Choong, Colin Hislop, Theo Heller, Chris Koh, Jeffrey Glenn, Tarik Asselah, Saeed Hamid, Ohad Etzion. Characterization of hepatitis D virus RNA and hepatitis B surface antigen kinetics during pegylated interferon-alpha monotherapy: The D-LIVR study. Journal of Hepatology, 2024 Vol 80 (S1): S800-801. Ashish Goyal, Ohad Etzion, Kimberly Page, Tatyana Kushner, Yedidya Saiman, Scott J Cotler, Harel Dahari. Modeling suggests that undetectable HCV at week 2 of DAA therapy could identify patients for shorter treatment duration. Journal of Hepatology, 2024 Vol 80 (S1): S832. Eric Tatara, Louis Shekhtman, Nicholson Collier, Marian Major, Jonathan Ozik, Basmattee Boodram, Harel Dahari. What happens to HCV incidence after WHO elimination goal is met? Agent-based modeling predicts sustained availability of direct-acting antivirals among people who inject drugs is required to prevent returning to pre-elimination levels. Journal of Hepatology, 2024 Vol 80 (S1): S43. (Oral Talk) Ashish Goyal, Takuro Uchida, Grace N Makokha, Hiromi Abe-Chayama, Yuji Ishida, Chise Tateno-Mukaidani, Harel Dahari, Kazuaki Chayama. Mathematical modeling of hepatitis B and D viral kinetics during coinfection in humanized mice suggests differences in their infectivity. Journal of Hepatology, 2024 Vol 80 (S1): S735-736. Adquate Mhlanga, Harel Dahari, Leeor Hershkovich, Scott J. Cotler, Ingrid Choong, Colin Hislop, Theo Heller, Chris Koh, Jeffrey Glenn, Tarik Asselah, Saeed Hamid, Ohad Etzion. Modeling dual antiviral activity of lonafarnib to explain hepatitis D virus RNA negativity 24 weeks after end of therapy despite RNA positivity at end of therapy: The D-LIVR study. Journal of Hepatology, 2024 Vol 80 (S1): S814 Biology and Medicine Through Mathematics Conference May 15-17, 2024 Richmond, VA Adquate Mhlanga, Ohad Etzion, Harel Dahari. A mathematical modeling study on HDV RNA, ALT, and HBsAg dynamics reveals dual mechanisms of peginterferon-lambda Mary-Ellen Mackesy-Amiti, Alexander Gutfraind, Eric Tatara, Nicholson T. Collier, Scott J. Cotler, Kimberly Page, Jonathan Ozik, Basmattee Boodram, Marian Major, Harel Dahari. Bridging the gap between controlled human infection models and real-word testing using computational modeling of randomized hepatitis C vaccine trials. (Oral talk) 74th Annual Meeting of the American Association for the study of Liver Diseases Nov 10-14, 2023 Boston, MA Ashish Goyal, Yuji Ishida, Chise Tateno, Andrew Vaillant, Scott J. Cotler, Kazuaki Chayama, Harel Dahari. Mathematical modeling of HBV kinetics in humanized mice suggests that NA blocks not only rcDNA production but also pgRNA synthesis. Hepatology 2023, 78(Suppl. 1): S530-S531. Leeor Hershkovich, Harel Dahari, Scott J. Cotler, Ingrid Choong, Colin Hislop, Ophir Dahari, Theo Heller, Christopher Koh, Jeffrey Glenn, Tarik Asselah, Saeed Hamid, Ohad Etzion. Characterization of HDV RNA kinetic patterns during treatment: The D-LIVR Phase 3 Study. Late-breaking abstract# 5023. Hepatology 2024, 79:E55-56. Sarah Duehren, Takuro Uchida, Masataka Tsuge, Nobuhiko Hiraga, Abu Fahad Abbasi, Ohad Etzion, Jeffrey Glenn; Christopher Koh, Theo Heller, Scott J. Cotler, Kazuaki Chayama, Harel Dahari. Evaluating the Efficacy of Pegylated IFN-λ and IFN-α Treatments on HBV and HDV Infections in Humanized Mice. Hepatology 2023, 78(Suppl. 1): S570. Christina Park, Julian Hercun, Harel Dahari, Ohad Etzion, Saeed S. Hamid, Edward J. Gane, Yoav Lurie, Farial Rahman, David Yardeni, Pallavi Surana, Colin Hislop, Ingrid Choong, Jeffrey Glenn, Theo Heller and Christopher Koh. Understanding the antiviral effects of peginterferon lambda with and without ritonavir boosted lonafarnib in chronic hepatitis D infection. Hepatology 2023, 78(Suppl. 1): S412. E. Fabian Cardozo-Ojeda, Sarah Duehren, Scott J. Cotler, Saeed S. Hamid, Yoav Lurie, Edward Gane, Anat Nevo-Shor, David Yardeni, Ingrid Choong, Jeffrey Glenn, Harel Dahari, Ohad Etzion. Mathematical modeling of HDV RNA, ALT and HBsAg kinetics suggests a dual mode of action of peginterferon lambda: The LIMT-1 Study. Hepatology 2023, 78(Suppl. 1): S579-S580. Adquate Mhlanga, Rami Zakh, Sarah Duehren, Alexander Churkin, Vladimir Reinharz, Danny Barash, Jeffrey Glenn, Ohad Etzion, Scott J. Cotler, Cihan Yurdaydin, Harel Dahari. Understanding the interplay between HDV RNA, HBV DNA and HBsAg during lonafarnib-based therapy via mathematical modeling: The LOWR HDV-1 Study. Hepatology 2023, 78(Suppl. 1): S591-S592. Eric Tatara, Qinyun Lin, Jonathan Ozik, Marynia Kolak, Nicholson Collier, Dylan Halpern, Luc Anselin, Harel Dahari, Basmattee Boodram, John Schneider. Optimizing methadone provider locations for reducing syringe sharing behavior and HCV transmission risk among persons who inject drugs in metropolitan Chicago. Hepatology 2023, 78(Suppl. 1): S698-S699. Eric Tatara, Louis Shekhtman, Nicholson Collier, Basmattee Boodram, Jonathan Ozik, Harel Dahari. Hybrid agent-based and viral kinetics modeling of hepatitis C micro-elimination among people who inject drugs with direct-acting antivirals in metropolitan Chicago. Hepatology 2023, 78(Suppl. 1): S688-S689. Ari Josephson, Yuji Ishida, Adquate Mhlanga, Zhenzhen Shi, Chise Tateno-Mukaidani, Jordan J Feld, Harel Dahari, Kazuaki Chayama. Modeling HCV kinetics from inoculation to steady state in SCID humanized mice predicts a partial block of viral production possibly due to an early stage of innate immune response. Hepatology 2023, 78 (Suppl. 1): S749-S750. Models of Infectious Disease Agent Study (MIDAS) Oct 29-31, 2023 Atlanta, Georgia Zhenzhen Shi, Adam Burns, Evan Cudone, Karina Durso-Cain, Nicholson Collier, Frederik Graw, Jonathan Ozik, Susan L. Uprichard, Harel Dahari. Modeling cell-to-cell spread of hepatitis C viral infection in vitro using agent-based modelling approach. 29th International Symposium on HCV, Flaviviruses and related Viruses Oct 1-4, 2023 Atlanta, Georgia Zhenzhen Shi, Xin Zhang, Niels Cremers, Johan Neyts, Harel Dahari, Suzanne Kaptein. Characterizing of hepatitis E virus infection in a rat model with and without ribavirin interventions. Eric Tatara, Louis Shekhtman, Nicholson Collier, Jonathan Ozik, Harel Dahari. Hybrid agent-based and viral kinetics modeling of hepatitis C micro-elimination among people who inject drugs with direct-acting antivirals in metropolitan Chicago. Ari Josephson, Yuji Ishida, Adquate Mhlanga, Zhenzhen Shi, Chise Tateno-Mukaidani, Jordan J Feld, Harel Dahari, Kazuaki Chayama. Insights into early acute HCV Infection in uPA-SCID Mice with Humanized Livers versus Chimpanzees using Mathematical Modelling Approach. The HBV International meeting Sept 19-23, 2023 Kobe, Japan Takuro Uchida, Sarah Duehren, Masataka Tsuge, Nobuhiko Hiraga, Susan Uprichard, Ohad Etzion, Jeffrey Glenn; Christopher Koh, Theo Heller, Scott J. Cotler, Kazuaki Chayama, Harel Dahari. Evaluating the Efficacy of Pegylated IFN-λ and IFN-α Treatments on HBV and HDV Infections in Humanized Mice. The International Liver Congress, annual meeting of the European Association for the Study of the Liver (EASL) June 21-24, 2023 Vienna, Austria Sarah Duehren, Louis Shekhtman, Scott J Cotler, Stephan Aberle, Thomas Reiberger, Peter Ferenci, Harel Dahari. Modeling-based response-guided therapy with bulevirtide monotherapy for chronic hepatitis D to identify patients for finite treatment duration. Journal of Hepatology, 2023 Vol 78 (S1):S1170-1.) Zhenzhen Shi, Xin Zhang, Niels Cremers, Johan Neyts, Harel Dahari, Suzanne Kaptein. Rat hepatitis E virus infection in a rat model has multiphasic viral replication kinetics. Journal of Hepatology, 2023 Vol 78 (S1):S1038-9. American Association for the Study of Liver Diseases (AASLD) Digital Liver Meeting Nov 4-8, 2022 Washington DC, USA Louis Shekhtman, Scott J Cotler, Elisabetta Degasperi, Maria Paola Anolli, Sara Colonia Uceda Renteria, Dana Sambarino, Marta Borghi, Riccardo Perbellini, Floriana Facchetti, Ferruccio Ceriotti, Pietro Lampertico, Harel Dahari. Modelling HDV kinetics under entry-inhibitor Bulevirtide suggests the existence of two HDV-infected cell populations: implications for response-guided therapy. Hepatology 2023, 77:E144. AASLD 2022 - Late-breaking abstract# 5031 Abu Abbasi, Harel Dahari, Nyingi Kemmer, Scott J Cotler, Miguel Malespin. Evaluating Pitfalls Within the Hepatology Training Pipeline. Hepatology 2022, Vol 76 (Suppl. 1): S1071-S1072. Richard Chiu, Eric R. Tatara, Mary-Ellen Mackesy-Amit, Basmattee Boodram, Jonathan Ozik, Harel Dahari, Alexander Gutfraind. Equitable recruitment to HCV vaccine clinical trials while reducing required sample size in Chicago area. Hepatology 2022, Vol 76 (Suppl. 1): S402-S403. Zhenzhen Shi, Xin Zhang, Niels Cremers, Johan Neyts, Harel Dahari, Suzanne Kaptein. Rat hepatitis E virus infection in a rat model has multiphasic viral replication kinetics. Journal of Hepatology, 2023 Vol 78 (S1):S1038-9. 2022 International HBV meeting "Molecular Biology of hepatitis B viruses" Sep 18-22, 2022, Paris, France Sarah Duehren, Louis Shekhtman, Scott J Cotler, Stephan Aberle, Thomas Reiberger, Peter Ferenci, Harel Dahari. Modeling-based response-guided therapy with bulevirtide monotherapy for chronic hepatitis D to identify patients for finite treatment duration. Journal of Hepatology, 2023 Vol 78 (S1):S1170-1.) S. Maya, L. Hershkovich, E. F. Cardozo-Ojeda, E. Shirvani-Dastgerdi, J. Srinivas, L. Shekhtman, S.L. Uprichard, A. Berneshawi, T.R. Cafiero, H. Dahari, A. Ploss. Mathematical modeling of early hepatitis D virus (HDV) kinetics in transgenic-hNTCP mice reveals biphasic decline post inoculation. Leeor Hershkovich, Louis Shekhtman, Scott J Cotler, Mathias Jachs, Stephan Aberle, Thomas Reiberger, Peter Ferenci, Harel Dahari. Entry-inhibitor Bulevirtide may interfere with hepatitis D virus clearance from circulation. 20th International Conference of Numerical analysis and Applied Mathematics (ICNAAM) Sep 19-25, 2022 Heraklion, Crete, Greece Adquate Mhlanga, Rami Zakh, Alexander Churkin, Vladimir Reinharz, Harel Dahari, Danny Barash. Towards an improved mathematical model for HDV-HBV interaction. 28th International Symposium on HCV, Flaviviruses and related Viruses July 6-9, 2022 Ghent, Belgium Zhenzhen Shi, Yuji Ishida, Nicholson T Collier, Michio Imamura, Chise Tateno-Mukaidani, Jonathan Ozik, Jordan J Feld, Harel Dahari, Kazuaki Chayama. Modeling acute HCV infection kinetics in humanized mice. The International Liver Congress, 57th annual meeting of the European Association for the Study of the Liver (EASL) June 22-26, 2022 London, UK Louis Shekhtman, Harel Dahari, Scott J. Cotler, Elisabetta Degasperi, Maria Paola Anolli, Sara Colonia Uceda Renteria, Dana, Sambarino, Marta Borghi, Riccardo Perbellini, Floriana Facchetti, Ferruccio Ceriotti, Pietro Lampertico. Most patients with advanced cirrhosis treated with bulevirtide monotherapy have a non-monophasic HDV RNA decline pattern: an interim kinetic analysis of real-life setting. Journal of Hepatology 2022 vol 77 (S1): S874 Leeor Hershkovich, Louis Shekhtman, Michel Bazinet, Mark Anderson, Mary Kuhns, Gavin Cloherty, Scott J. Cotler, Andrew Vaillant, Harel Dahari. Characterizing of hepatitis B virus serum RNA kinetics during combination therapy of TDF plus pegylated interferon alfa-2a with and without nucleic acid polymers. Journal of Hepatology 2022 vol 77 (S1): S851-S852 Sarah Duehren, Christopher Koh, Julian Hercun, Farial Rahman, Pallavi Surana, Anusha Vittal, Gil Ben-Yakov, Walter Chunwei Lai, Ohad Etzion, Scott J. Cotler, Jeffrey S. Glenn, Harel Dahari, Theo Heller. Lonafarnib combination with peginterferon Lambda diminished triphasic HDV kinetic pattern seen under Lambda monotherapy: the LIFT HDV Study. (Oral talk). Journal of Hepatology 2022 vol 77 (S1): S70-S71. E Fabian Cardozo-Ojeda, Sarah Duehren, Saeed S. Hamid, Yoav Lurie, Edward Gane, Nimrah Bader, David Yardeni, Anat Nevo-Shor, Saleh M. Channa, Minaz Mawani, Om Parkash, Ingrid Choong, Scott J. Cotler, Jeffrey Glenn, Harel Dahari, Ohad Etzion. Mathematical modeling of HDV RNA kinetics suggests high peginterferon-lambda efficacy in blocking viral production: Insights from the LIMT-1 study. [PDF] Journal of Hepatology 2022 77 (S1): vol S859 Ashish Goyal, Alex Churkin, Danny Barash, Scott J Cotler, Amir Shlomai, Ohad Etzion, Harel Dahari. Simplifying mathematical-based response guided therapy for reducing duration of direct acting antivirals in chronic hepatitis C infected patients. Journal of Hepatology 2022 vol 77 (S1): S588 Zhenzhen Shi, Yuji Ishida, Nicholson T Collier, Michio Imamura, Chise Tateno-Mukaidani, Jonathan Ozik, Jordan J Feld, Harel Dahari, Kazuaki Chayama. Understanding acute HCV infection kinetics in humanized mice via an agent-based modelling approach. Journal of Hepatology 2022 vol 77 (S1): S252. American Transplant Congress (ATC) June 4-8, 2022 Boston, MA, USA Duehren S, Cotler SJ, Dahari H, Shi Z, Joyce, C, Fernandez LF, Lee DD. Oxygen saturation during donor warm ischemia time and outcome of donation after circulatory death (DCD) liver transplantation: a review of 1207 cases. https://atcmeetingabstracts.com/abstract/oxygen-saturation-during-donor-warm-ischemia-time-and-outcome-of-donation-after-circulatory-death-dcd-liver-transplantation-a-review-of-1207-cases/ . (Oral Talk) EASL, Viral Hepatitis Elimination 2022 – Towards a hepatitis-free world, Virtual Feb 24-25, 2022 Basmattee boodram, Harel Dahari, Jonathan Ozik, Alexander Gutfraind, Nicholson Collier, Desarae Echevarria, Scott Cotler, Marian Major, Eric Tatara. Modeling hepatitis C micro-elimination among people who inject drugs with direct-acting antivirals in metropolitan Chicago. https://easl.eu/wp-content/uploads/2022/02/Viral-Hepatitis-Elimination-2022-Abstract-book.pdf American Association for the Study of Liver Diseases (AASLD) Digital Liver Meeting Nov 12-15, 2021 Mary-Ellen Mackesy-Amiti, Alexander Gutfraind, Eric Tatara, Nicholson Collier, Scott Cotler, Kimberly Page, Jonathan Ozik, Basmattee Boodram, Marian Major, Harel Dahari. Simulations of HCV vaccine trials demonstrate effects of background incidence and unbalanced exposure that can impact vaccine efficacy. Hepatology 2021, Vol 74 (1) (Suppl): 604A. (AASLD Presidential Poster of Distinction) Zhenzhen Shi, Masataka Tsuge, Takuro Uchida, Yuji Teraoka, Nicholson T. Collier, Susan Uprichard, Jonathan Ozik, Yuji Ishida, Chise Tateno, Harel Dahari, Kazuaki Chayama. Understanding HBV spread in primary human hepatocytes via an agent-based modelling approach. Hepatology 2021, Vol 74 (1) (Suppl): 537A. Leeor Hershkovich, Louis Shekhtman, Michel Bazinet, Victor Pântea, Gheorge Placinta, Iurie Moscalu, Scott J. Cotler, Andrew Vaillant, Harel Dahari. Rapid monophasic HBsAg decline during NAP-based therapy predicts functional cure. Hepatology 2021, Vol 74 (1)(Suppl):514A-515A (AASLD Presidential Poster of Distinction) Leeor Hershkovich, Louis Shekhtman, Michel Bazinet,Victor Pântea, Gheorghe Placinta, Iurie Moscalu, Mark Anderson, Jeffrey Gersch, Vera Holzmayer, Mary Kuhns,Gavin A Cloherty, Scott J Cotler, Andrew Vaillant and Harel Dahari. Serum HBV DNA, pregenomic RNA, HBsAg, HBcrAg and ALT kinetic characterization during 24-week tenofovir disoproxil fumarate monotherapy. Hepatology 2021, Vol 74 (1) (Suppl):494A-495A. 5th Digital Workshop on Virus Dynamics October 2021 Jay Srinivas, Stephanie Maya, Benjamin Y. Winer, Harel Dahari, Alexander Ploss. Mathematical modeling of early hepatitis D virus kinetics in transgenic-hNTCP mice. (Oral talk) https://www.fredhutch.org/en/events/workshop-on-virus-dynamics/agenda.html HBV International Meeting Toronto, Canada September 2021 Stephanie Maya, Jay Srinivas, Elham Shirvani-Dastgerdi, Louis Shekhtman, Susan L. Uprichard, Andrew Berneshawi, Thomas R. Cafiero, Harel Dahari, Alexander Ploss. Mathematical modeling of early hepatitis D virus kinetics in transgenic-hNTCP mice. 27th International Symposium on Hepatitis C Virus and Related Viruses (HCV 2021), a virtual conference July 6-9, 2021 Eric Tatara, Alexander Gutfraind, Nicholson T. Collier, Desarae Echevarria, Scott J. Cotler, Marian Major, Basmattee Boodram, Jonathan Ozik, Harel Dahari, Basmattee Boodram. Re-treatment with direct-acting antivirals policy is needed to eliminate Hepatitis C among persons who inject drugs. (Oral Presentation). PLOS ONE 202S. https://doi.org/10.1371/journal.pone.0264983 Susan L. Uprichard, Karina Durso-Cain, Peter Kumberger, Yannik Schalte, Theresa Fink, Harel Dahari, Jan Hasenauer, Frederik Graw. HCV spread kinetics reveal varying contributions of transmission modes to infection dynamics. The Digital International Liver Congress, 56th annual meeting of the European Association for the Study of the Liver (EASL) June 23-26, 2021 Leeor Hershkovich, Louis Shekhtman, Michel Bazinet,Victor Pântea, Gheorge Placinta, Iruie Moscalu, Valentin Cebotarescu, Lilia Cojuhari, Pavlina Jimbei, Liviu Iarovoi, Valentina Smesnoi, Tatiana Musteata, Alina Jucov, Scott Cotler, Andrew Vaillant, Harel Dahari. HBsAg, anti-HBs and ALT kinetic characterization during NAP based combination therapy of HBeAg negative chronic hepatitis B infection. Journal Hepatology 2021 vol 72(2): S750-1 Stephanie Kriss, Alex Churkin, Asher Uziel, Jay Srinivas, Scott Cotler, Ohad Etzion, Amir Shlomai, Danny Barash, Harel Dahari. Real-time utility of response-guided DAA therapy for hepatitis C based on a mathematical modeling approach: database formation and machine learning methods. Journal Hepatology 2021 vol 72(2): S801-2. Alexander Gutfraind, Mary-Ellen Mackesy-Amiti, Eric Tatara, Nicholson Collier, Scott Cotler, Kimberly Page, Jonathan Ozik, Basmattee Boodram, Marian Major, Harel Dahari. Simulations of HCV vaccine trials reveal opportunities to re-evaluate vaccine efficacy. Journal Hepatology 2021 vol 72(2): S768. American Association for the Study of Liver Diseases (AASLD) Digital Liver Meeting Nov 13-16, 2020 Jay Srinivas, Stephanie Maya, Benjamin Y. Winer, Harel Dahari, Alexander Ploss. Characterization of serum HBV kinetics from inoculation to steady state in mice engrafted with components of a human immune system (HIS) and/or human hepatocytes (HEP). (Poster of Distinction). Hepatology 2020; Vol. 72, no. 1 (SUPPL): 509A-510A. Christopher Koh, Julian Hercun, Farial Rahman, Amy Wen-Chun Huang, Ben L. Da, Pallavi Surana, Devika Kapuria, Yaron Rotman, Anusha Vittal, Christy Ann Gilman, Gil Ben-Yakov, Walter Chunwei Lai, Harel Dahari, Jeffrey S. Glenn, and Theo Heller. A Phase 2 Study of Lonafarnib, Ritonavir and Peginterferon Lambda for 24 Weeks: End-of-Study Results from the LIFT HDV Study. (Oral talk , late breaking). Hepatology 2020, accepted. Addiction Health Services Research Conference (AHSR Virtual) Oct 14-16, 2020 Jonathan Ozik, Marynia Kolak, Qinyun Lin, Harel Dahari, Basmattee Boodram, John Schneider, Eric Tatara, Nicholson Collier. Measuring social and spatial inequities in access to opioid use disorder treatment for reducing HIV and HCV transmissions . (Publication ) Addict Sci Clin Pract 2020, 15(Suppl 2):A37 The Digital International Liver Congress, 55th annual meeting of the European Association for the Study of the Liver (EASL) August 27-29, 2020 Preeti Dubey, Stephanie Maya, Elham Shirvani-Dastgerdi, Hannah Shanes, Susan L. Uprichard, Andrew Berneshawi, Harel Dahari*, Alexander Ploss*. Mathematical modeling of early hepatitis D virus kinetics in transgenic-hNTCP mice. (ePoster oral talk) Journal of Hepatology 2020 vol. 73, S837-838. Christopher Koh, Julian Hercun, Farial Rahman, Amy Wen-Chun Huang, Ben L. Da, Pallavi Surana, Devika Kapuria, Yaron Rotman, Anusha Vittal, Christy Ann Gilman, Gil Ben-Yakov, Walter Chunwei Lai, Harel Dahari, Jeffrey S. Glenn, and Theo Heller. A Phase 2 Study of Lonafarnib, Ritonavir and Peginterferon Lambda for 24 Weeks: End-of-Treatment Results from the LIFT HDV Study. (Late breaking) Journal of Hepatology 2020 vol. 73, S130. Society of Mathematical Biology (SMB) 2020 Annual (Virtual) Meeting August 17-20, 2020 Preeti Dubey, Stephanie Maya, Elham Shirvani-Dastgerdi, Hannah Shanes, Susan L. Uprichard, Andrew Berneshawi, Alexander Ploss*, Harel Dahari*. Modeling early hepatitis D virus kinetics in transgenic-hNTCP mice. (Oral talk) Society for Prevention Research (SPR) annual meeting, Virtual Conference July 21-23, 2020 Basmattee Boodram, Eric Tatara, Alexander Gutfraind, Nicholson T. Collier, Scott J. Cotler, Marian Major, Jonathan Ozik, Harel Dahari. Towards achieving WHO’s hepatitis C incidence reduction objective by 2030 among persons who inject drugs: Modeling reveals need for retreatment. 70th Annual Meeting of the American Association for the study of Liver Diseases Boston, Ma, USA November 8-12, 2019 Christopher Koh, Ben L. Da, Pallavi Surana, Amy Wen-Chun Huang, Devika Kapuria, Yaron Rotman, Anusha Vittal, Christy Ann Gilman, Gil Ben-Yakov, Walter Chun-wei Lai, Farial Rahman, Julian Hercun, Harel Dahari, Jeffrey S. Glenn, and Theo Heller. A Phase 2 Study of Lonafarnib, Ritonavir and Lambda Interferon for 24 weeks: Interim End-of-Treatment Results from the LIFT HDV Study. Hepatology 2019; accepted (Oral Late breaking). Ohad Etzion, Sarah Duehren, Saeed Sadiq Hamid, Yoav Lurie, Edward Gane, Nimrah Bader, David Yardeni, Anat Nevo-Shor, SM Channa, Minaz Mawani, Om Parkash, Kyunghee Yang, Diane Longo, Susan L. Uprichard; Robert G. Gish, Scott J. Cotler; Jeffrey Glenn, David Apelian, Harel Dahari. Characterization of HDV, HBsAg and ALT kinetics under Peginterferon-Lambda Monotherapy: The Phase 2 LIMT Study. Hepatology 2019; accepted (Late breaking). Swikriti Dasgupta, Michio Imamura, Takashi Nakahara, Masataka Tsuge, Alexander Churkin, David Yardeni, Ohad Etzion, Susan L. Uprichard, Danny Barash, Scott J. Cotler, Harel Dahari*, Kazuaki Chayama*. Modeling-based response-guided therapy under glecaprevir/pibrentasvir may optimize duration of therapy in patients with compensated cirrhosis. Hepatology 2019; Vol 70(Suppl1):931A. Kevin Walsh, Marianne Martinello, Alexander Churkin, Sijia Lou, Tanya Applegate, Ohad Etzion, Susan L. Uprichard, Scott J. Cotler, Danny Barash, Gail Matthews, Harel Dahari. Modeling indicates 100% negative predictive value of achieving cure in subjects with recent HCV infection treated for 6 weeks with sofosbuvir and ribavirin: The DARE II Study. Hepatology 2019; Vol 70(Suppl1):969A-970A. Elham Shirvani-Dastgerdi, Hannah Shanes, Andrew Berneshawi, Harel Dahari*, Alexander Ploss*.HDV RNA decline post inoculation in human NTCP transgenic mice is biphasic. Hepatology 2019; Vol 70(Suppl1):623A-624A. 70th Annual Meeting of the American Association for the study of Liver Diseases. Boston, Ma, USA, Nov 8-12, 2019 Preeti Dubey, Yuji Ishida, Masataka Tsuge, Mikaru Yamao, Chise Tateno, Susan L Uprichard, Harel Dahari*, Kazuaki Chayama*. Understanding early HBV kinetics during infection and treatment in primary human hepatocytes: a data-driven mathematical modeling approach. Hepatology 201; Vol 70(Suppl1):178A. (Oral talk) Alexander Gutfraind, Eric Tatara, Nicholson T. Collier, Scott J. Cotler, Stephen Feinstone, Kimberly Page, Jonathan Ozik, Basmattee Boodram, Marian Major, Harel Dahari. Simulation of HCV vaccine clinical trials reveals opportunities and challenges for candidate HCV vaccines. Hepatology 2019; Vol 70 (Suppl1):990A. 4th Workshop on viral dynamics Paris, France October 2019 Peter Kumberger, Karina Durso-Cain, Yannik Schälte, Theresa Fink, Harel Dahari, Jan Hasenauer, Susan L. Uprichard, Frederik Graw. Hepatitis C virus spread kinetics reveal varying contributions of transmission modes to infection dynamics. Abstract (Oral Talk) 26th International Symposium on HCV and related Viruses Seoul, South Korea October 5-8, 2019 Dahari H*, Etzion O*, Yardeni D, Issachar A, Nevo-Shor A, Cohen-Naftaly M, Uprichard SL, Sneh Arbib, Munteanu D, Braun M, Cotler SJ, Abufreha N, Mor O, Shlomai A. Modeling based response guided therapy with DAA shortens treatment duration in HCV treated patients. (Oral Talk) Eric Tatara, Alexander Gutfraind, Nicholson T. Collier, Scott J. Cotler, Marian Major, Basmattee Boodram, Jonathan Ozik, Harel Dahari. Agent-based modeling of persons who inject drugs in metropolitan Chicago suggests that re-treatment with antivirals of persons who are re-infected with Hep C is critical to achieve the WHO incidence reduction objective by 2030. 2019 International HBV meeting “Molecular Biology of hepatitis B viruses Melbourne, VIC, Australia October 1-5, 2019 Ghent, Belgium Masataka Tsuge, Ken Tsushima, Nobuhiko Hiraga, Takuro Uchida, Michio Imamura, C. Hayes Nelson, Harel Dahari, Susan L. Uprichard, Kazuaki Chayama. Analysis of the association between HBV infection and long term trends in intrahepatic gene expression. Delaina May, Yuji Ishida, Masataka Tsuge, Mikaru Yamao, Chise Tateno, Harel Dahari, Kazuaki Chayama and Susan L Uprichard. HBV infection and spread in HepG2-NTCP cells initiated by low MOI inoculation in the absence of PEG 17th International Conference of Numerical Analysis and Applied Mathematics (ICNAAM 2019) Rhodes, Greece September 23-28, 2019 Alexander Churkin, Vladimir Reinharz, Stephanie Lewkiewicz, Harel Dahari, Danny Barash. HCVMultiscaleFit: A Simulator for Parameter Estimation in Multiscale Models of Hepatitis C Virus Dynamics. (Oral talk) SIAM Conference on the Life Sciences (LS18) Minneapolis, Minnesota, USA August 6-9, 2019 Danny Barash, Vladimir Reinharz, Alexander Churkin, Harel Dahari. Numerical Methods for Solving and Optimizing Multiscale Models of Hepatitis C Virus Dynamics (Oral talk) Annual meeting of the Theoretical Biology and the Society for Mathematical Biology Montreal, Canada July 21-26, 2019 Mini-Symposia titled: “Hepatitis B viral dynamics: mathematical and numerical methods”. Vladimir Reinharz, Danny Barash, and Harel Dahari. PDE modeling simulations and fitting methods for understanding hepatitis B virus infection in humanized mice. (Oral talk) Preeti Dubey, Yuji Ishida, Masataka Tsuge, Mikaru Yamao, Chise Tateno, Susan L Uprichard, Kazuaki Chayama* Harel Dahari. Modeling hepatitis B virus infection in primary human hepatocytes. (Oral talk) The International Liver Congress, 54th annual meeting of the European Association for the Study of the Liver Vienna, Austria April 10-14, 2019 Yuji Ishida, Preeti Dubey, Masataka Tsuge, Mikaru Yamao, Chise Tateno, Susan L Uprichard, Harel Dahari*, Kazuaki Chayama*. Characterization of HBV kinetics during infection and treatment in primary human hepatocytes. Journal Hepatology 2019; Vol. 70, issue 1. Suppl 1, e701. https://doi.org/10.1016/S0618-8278(19)31399-4 Upendra Kumar, Rafaela VP Ribeiro, Susan L. Uprichard, Marcos Galasso, Atul Humar, Marcelo Cypel, Scott J. Cotler, Harel Dahari*, Jordan J. Feld*. Modeling early viral kinetics during observed HCV acute infection in post lung transplantation recipients. Journal Hepatology 2019; Vol. 70, issue 1. Suppl 1, e494–e495. https://doi.org/10.1016/S0618-8278(19)30971-5 (oral ePoster) Louis Shekhtman, Scott J. Cotler, Susan L. Uprichard, Michel Bazinet, Victor Pantea, Valentin Cebotarescu, Lilia Cojuhari, Pavlina Jimbei, Adalbert Krawczyk, Andrew Vaillant, Harel Dahari. Understanding HDV and HBsAg kinetics during nucleic acid polymer REP 2139 mono-therapy in HBeAg-negative chronic HBV/HDV co-infected patients via mathematical modeling. Journal Hepatology 2019; Vol. 70, issue 1. Suppl 1, e463. https://doi.org/10.1016/S0618-8278(19)30913-2 2019 AASLD/EASL HCV Special Conference Miami, FL, USA February 1‐2, 2019 Eric Tatara, Alexander Gutfraind, Nicholson T. Collier, Scott J. Cotler, Marian Major, Basmattee Boodram, Jonathan Ozik, Harel Dahari. Agent-based modeling of persons who inject drugs in metropolitan Chicago suggests that re-treatment with antivirals of persons who are re-infected with Hep C is critical to achieve the WHO incidence reduction objective by 2030 69th Annual Meeting of the American Association for the study of Liver Diseases San Francisco, CA, USA, Nov 9-13, 2018 Etzion O*, Dahari H*, Yardeni D, Issachar A, Nevo-Shor A, Cohen-Naftaly M, Uprichard SL, Sneh Arbib O, Munteanu D, Braun M, Cotler SJ, Abufreha N, Mor O, Shlomai A. Response-guided therapy with DAA shortens treatment duration in 50% of HCV treated patients. Hepatology 2018; 68(6); 1468A – 1469A. (Late-Breaking # 34).https://doi.org/10.1002/hep.30353 25th International Symposium on HCV and related Viruses Dublin, Ireland Oct 8-11, 2018 Karina Durso-Cain, Peter Kumberger, Harel Dahari, Frederik Graw, Susan L. Uprichard. Dissecting the contribution of cell-to-cell spread to HCV infection dynamics 2018 International HBV meeting Molecular Biology of hepatitis B viruses Taormina (Messina), Italy Oct 3-6, 2018 Upendra Kumar, Takuro Uchida, Kevin Walsh, Michio Imamura, Atesmachew Hailegiorgis, Christopher Koh, Theo Heller, Jeffrey S. Glenn, Susan L. Uprichard, Kazuaki Chayama, Harel Dahari. Preliminary analysis of HBV and HDV dynamics during acute co-infection in uPA/SCID chimeric mice using an agent-based modeling approach. Global Hepatitis Summit Toronto, Canada May 2018 Binhui Deng, Sijia Lou, Preeti Dubey, Ohad Etzion, Kazuaki Chayama, Susan L Uprichard, Mark Sulkowski, Scott J Cotler, Harel Dahari. Modeling time to cure after short-duration treatment for chronic HCV with daclatasvir, asunaprevir, beclabuvir and sofosbuvir: The FOURward Study. (Travel award) Journal Viral Hepatitis, 2018, Vol 25 Suppl S2; pg 58. https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvh.45_12923 VA Research Week May 14 – 18, 2018 Sarah Rahman, Kushal Shah, Veronica Loy, Cara Joyce, Harel Dahari, Roshani Naidu, Steve Scaglione and Susan L. Uprichard. Assessing Ezetimibe as a Safe and Efficacious Treatment for Chronic Hepatitis C The International Liver Congress, 53rd annual meeting of the European Association for the Study of the Liver Paris, France April 11-15, 2018 Preeti Dubey, Christopher Koh, Pallavi Surana, Susan L. Uprichard, Ma Ai Thanda Han, Nancy Fryzek, Gitanjali Subramanya, Devika Kapuria, Ohad Etzion, Varun Takyar, Yaron Rotman, Cihan Yurdaydin, Jeffrey S. Glenn, Scott J. Cotler, Theo Heller and Harel Dahari. Pharmacokinetics and pharmacodynamics modeling of ritonavir boosted lonafarnib therapy in HDV infected patients: A phase 2 LOWR HDV-3 study. Journal Hepatology 2018; Vol. 68, Suppl 1, S508 Upendra Kumar, Takuro Uchida, Atesmachew Hailegiorgis, Nobuhiko Hiraga, Kevin Walsh, Michio Imamura, Christopher Koh, Theo Heller, Jeffrey S. Glenn, Susan L. Uprichard, Kazuaki Chayama, Harel Dahari. Understanding HDV and HBV dynamics during acute co-infection in humanized uPA/SCID chimeric mice using an agent-based modeling approach. Journal Hepatology 2018; Vol. 68, Suppl 1, S783 Atesmachew Hailegiorgis, Yuji Ishida, Michio Imamura, Nobuhiko Hiraga, Hiroshi Yokomichi , Chise Tateno, Susan L. Uprichard, Kazuaki Chayama ,Harel Dahari. Understanding the multiphasic viral kinetics of cute HBV infection observed in humanized uPA/SCID mice using an agent-based modeling approach. Journal Hepatology 2018; Vol. 68, Suppl 1, S782-S783 Louis Shekhtman, Nathaniel Borochov, Scott J. Cotler, Leeor Hershkovich, Susan L. Uprichard, Mamun Al-Mahtab, Michel Bazinet, Andrew Vaillant, Harel Dahari. Modeling serum HBsAg, HBV DNA and transaminase kinetics during REP 2139 monotherapy in chronic HBeAg+ HBV infection. Journal Hepatology 2018; Vol. 68, Suppl 1, S508

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  • People | DahariLab

    Harel Dahari, PhD Professor, Loyola University Chicago Principal Investigator, Division of Hepatology Co-Director Program for Experimental & Theoretical Modeling | AASLD Fellow | MIDAS | CETI I am a scientist focused on mathematical modeling. I believe solving complex problems requires global, multidisciplinary collaborations. Dahari Lab believes that a diverse community of students, faculty, trainees, and staff promotes innovative research, increases quality of patient care, and provides the richest set of viewpoints for solving complex problems. Administrator Marie Go Morelos, MS Senior Research Associate William C Bietsch, MA Postdoctoral Fellow Adquate Mhlanga, PhD Research Associate Louis Shekthman, PhD Adjunct Research Associate Ashish Goyal, PhD Senior Researcher Ronen Borenstein, PhD Research Associate Professor Sasha Gutfraind, PhD Research Assistant Professor Zhenzhen (Tracy) Shi, PhD Research Volunteer Adam Burns, BS Research Volunteer Evan Cudone, BS Research Specialist Sarah Duehren, BS Research Volunteer Keshav Gandhi Research Specialist Leeor Hershkovich, BS Research Specialist Ori Wasserman Research Intern Aarim Khan, BS Lab Alumni Richard Chiu, B.S. Ates Hailegiorgis, PhD Abu Fahad Abbasi, MD Masataka Tsuge, PhD, MD Hiroshima University, Japan Riya Patell E. Fabian Cardozo-Ojeda , PhD Desarae Echevarria, M.S. Ari Josephson, BS Jay Srinivas, B.S. Vladimir Reinharz, PhD Daniel Kakon Hila Dahari Stephanie Kriss Evan Gorstein, B.S Erin Meger, PhD Ashbin Jaison, B.S Preeti Dubey , PhD Upendra Kumar, M.S Laetitia Canini, PhD Kevin Walsh, M.D Hannah Shanes Shayna Korol , M.S S wikriti Dasgupta , B.S Miko Vesovic , M.S Sarah Main Tje Lin, PhD Aadish Chopra, M.S Sijia Lou, M.Sc Oriel Borochov Narender Tanksala, M.S Marina Romadan, M.S Sarah Otis Nathaniel Borochov, B.S Binhui Deng , M.S Rahul Pipalia, M.S Swati Debroy , PhD Natasha Sansone, PhD Mughunandan Chandrasekar Premnath Ramanathan, M.S Ophir Dahari

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    Our Commitment to Diversity: Dahari Lab believes that a diverse community of students, faculty, trainees, and staff promotes innovative research, increases quality of patient care, and provides the richest set of viewpoints for solving complex problems. Since its inception, we have invested in a global network of research partnerships from a variety of disciplines with diverse backgrounds and experiences. Lab Members Bangladesh Canada China Colombia Ethiopia France Germany India Ireland Israel Japan Philippines Russia USA Zimbabwe Partners Australia Austria Belgium Brazil Canada China Italy Japan France Germany Israel Spain Turkey USA

  • Highlights | DahariLab

    Highlights HCV research with Dr. Charles Rice, 2020 Nobel Prize recipient. (2004-2007) Our (2004-2007) HCV research with Dr. Charles Rice, 2020 Nobel Prize recipient contributed to the following translational research which deepened knowledge of the HCV-host dynamic on the molecular level and during acute infection in chimpanzees. Hepatitis C virus kinetics and host responses associated with disease and outcome of infection in chimpanzees (2004) Mathematical modeling of primary hepatitis C infection: noncytolytic clearance and early blockage of virion production (2005) Mathematical modeling of subgenomic hepatitis C virus replication in Huh-7 cells. (2007) Large Scale RGT Clinical Trial Preview October 2020 Success in real-time patient therapy to be tested in larger HCV treatment clinical trial with Israeli research partners. Significant implications for healthcare cost, duration of treatment and patient-care. Harel Dahari's recent work was acknowledge at a conference in South Korea. Publication; Press Release; Conference Ultrashort HCV Time-to-Cure Results May 2020 Proof-of-concept HCV study yields promising results for a 4-week ultra-short, response-guided therapy treatment. Retrospective modeling of viral kinetics underscores the potential usefulness of a personalized modeling-based RGT approach to shorten the duration of treatment. Publication Promising Results for Transplant Recipients May 2020 Therapy combination prevents HCV infection in organ transplant recipient. Anti-viral treatment optimization results in milestone achievement in collaboration with Canadian cohort. For the patient, this results in cheaper, safer treatments, and removes the added risk of HCV while in post-transplant recovery [AASLD]. This comes at a time when HCV infection and mortality rates in younger populations are on the rise due to the ongoing opioid crisis [CDC]. Publication; Press Release; Comment HBV/HDV Research Advancement May 2020 Mathematical modeling leads to new insights in HBV/HDV research with biopharma firm Replicor. Defining Mode of Action helped unlock promising new therapy in development for HBV treatment as well as in patients coinfected with HDV. Publication; Replicor Press Release Principles of Cell Circuits for Tissue Repair and Fibrosis February 2021 DahariLab hosted Miri Adler, PhD from The Broad Institute of MIT and Harvard to discuss her research on the social behavior of cells during tissue repair and fibrosis. As part of her research, Dr. Adler developed a mathematical model to better understand the principles of this dynamic. ReplyForward Add reaction

  • HCV | DahariLab

    HCV Time to Cure: Personalizing Patient Care Through Individualized Treatment HCV Elimination The Key to Eliminating Hepatitis C: Reducing New Infections in Special Populations through Mathematical/Computational Modeling HCV Vaccine The Challenges of Developing and Applying an HCV Vaccine "Dahari Lab is committed to the WHO goal of global HCV elimination" Dahari Lab, through our partnerships, is making a direct impact on patients, moving from theory to the heart of patient care. For almost two decades, Hepatitis C virus (HCV) dynamic research centered on interferon alpha (IFN) therapy. The success rate averaged less than 50% with long treatment cycles of 48 weeks with serious side effects. Mathematical modeling was used retrospectively (not in real-time) to guide the duration of therapy (Current Hepatitis Reports). In 2015, we reached a significant milestone. Real-time modeling was used to predict the duration of the IFN-free treatment using silibinin + ribavirin. This was the first use of real-time mathematical modeling of HCV kinetics to tailor the duration of IFN-free therapy in a specific patient. This was a significant departure from the existing one-size-fits-all approach, allowing the patient to participate in shared decision-making for length of treatment (Liver Int). In 2014, IFN-free, all-oral, direct-acting antivirals (DAAs) were approved. These DAAs ushered in a new era of treatment resulting in an HCV cure rate in over 95% of infected patients. The World Health Organization (WHO) has recognized the need to prevent and control HCV infection, and proposed that HCV elimination was feasible by 2030 through reducing new chronic infections by 90% and HCV-related mortality by 65%. However, the high cost of these drugs is a major obstacle to achieving viral elimination. Results of previous retrospective studies on mathematical modeling of viral kinetics during early stages of DAAs therapy, have suggested that HCV can be cured with a shorter duration of treatment in a substantial proportion of patients. We continued to refine our research with DAAs and mathematical modeling targeting treatment duration and effectiveness (J Hepatology, PLoS One) as well as interventions in specialized patient populations (Liver Int., Journal of Infectious Diseases). A major milestone in our research is a completed proof of concept study that prospectively (in real-time) showed that response-guided therapy (RGT) modeling can be utilized for shortening DAAs duration (up to 50%) without compromising treatment efficacy. Implementation of this personalized form of treatment on a wider scale, may lead to significant cost-savings (up to 50%) and improved access to anti-HCV care. In 2020, a larger clinical trial is planned in cooperation with, and sponsored by the Israeli Ministry of Health (Scientific Reports). The modeling-based RGT has also been expanded to individuals with recent (<6 months) and acute ( Now that a more effective treatment via direct-acting antiviral agents (DAAs) is widely available for HCV, we have entered an era of refining the research in an effort to achieve cost-reduction and ease of treatment. The goal to eliminate HCV as defined by the World Health Organization (WHO) is not only possible, but well within reach by their target of 2030. However, it will only be achieved if treatments can be scaled and paired with strategies that address the characteristics of special groups and the need for re-treatment. Targeting larger populations with chronic infection is one of two tactics needed to achieve the elimination goal. The first tactic is reducing the prevalence (or number of cases) in the general population. It is the most basic strategy. The second is critical to finally eliminating HCV. This involves the ability to map, model and target special populations that represent a disproportionate number of new infections, reinfections or the transfer of infection. Dahari Lab has been at the forefront of modeling one of these special populations: people who inject drugs (PWID). Without an effective treatment strategy (cost, ease to administer, duration, identifying targets) this population, which represents a small percentage of the overall infections, will continue to reintroduce the virus and make elimination difficult to impossible. In our research we used mathematical modeling to predict that DAA treatment scale-up could dramatically reduce the prevalence of chronic HCV infection among PWID in Chicago. This population was identified and targeted due to its on-going high HCV transmission and reinfection rates (PLoS One). The WHO defines elimination as a reduction of HCV incidence by 90% by 2030. We used this parameter in our research to gauge the feasibility and select the factors to consider. In 2019, we published modeling outcomes for cost and reduction of HCV incidence in the population of PWID. The results showed that a 90% reduction is indeed possible through DAA-based treatments. The model produced data that was valuable for public health policy makers to understand the costs associated with various treatment rates, timelines, and their effectiveness (Vaccine). While DAA-based treatment is a very effective therapy in general for PWID, many factors within this community can cause serious setbacks. These factors include cost, restricted access to DAAs, and the risk of reinfection. Intervention strategies must address this dynamic and complex interplay for PWID (e.g. behavior, structure, access to clean needles, etc.) (Lancet Infct Dis). To better understand and map this population with greater depth and detail, we developed an agent-based model (ABM) for PWID in the Chicago metro area. ABM is a more sophisticated modeling that allowed us to create and map unique profiles to model behavior and outcomes. This data gave us deeper insights to make more detailed and relevant predictions at the individual level (such as geography, PWID network, ethnicity, and age) (PLoS One). We formalized this work as the HepCEP model (Hepatitis C Elimination in PWID) and the research was expanded with funding by the NIH. It allowed us to work in close partnership with Marian Major (FDA), Basmattee Boodram (UIC), and Jonathan Ozik (UofC & Argonne National Lab). The HepCEP model showed that, in the Chicago community, exploiting PWID network structures by targeting individuals who may have transmitted the infection helped reduce incidence and cost (through targeted DAA treatment). The benefit to running models is the range of scenarios and options that can be explored quickly to inform policy (2019 Winter Simulation Conference). Another significant finding is the impact of retreatment. The HepCEP model predicted that ignoring retreatment as a factor in the elimination strategy, cost, or duration of treatment will jeopardize achieving the WHO goal. These simulations showed that based on the parameters of the model, just under half the population would need retreatment with a small percentage of individuals needing as many as 7 retreatments. While it may lead the general public to question if retreatments are a waste of time and public money, the data confirms it is all interconnected. The model highlights the importance of a strategy that includes re-treatment of re-infected individuals in order to achieve significant reductions in incidence (ARXIV). Mathematical modeling has proved to be a critical tool for helping define the problem and all of its complexities. Paired with the innovations in DAA treatment and informed public policy, the commitment by the WHO to eliminate HCV is no longer a dream. Models indicate that the goal of hepatitis C virus (HCV) elimination by 2030 put forth by the World Health Organization is possible in theory. The reality is a bit more complicated. While it is possible through treatment alone without developing a vaccine, reinfections in specialty groups can cancel out any progress made in reducing HCV elsewhere in the population. Models have shown that a variety of treatment strategies yield just as many outcomes with a number of tradeoffs. This is confirmed in the data from models built to explore the impact of various treatment approaches to HCV. Developing a vaccine for HCV has many benefits that should not be seen as luxuries or an afterthought. An effective vaccine would reduce treatment cost and duration; prevent new cases; and allow research funding and focus to shift, all on a global scale. Our research at Dahari Lab, along with our partners/collaborators, has contributed to each of these areas. Our 2019 research on treatment and intervention in the special population of people who inject drugs (PWID) in Chicago used mathematical modeling to show the impact of four different treatment interventions. The results showed a combination of direct-acting antivirals (DAAs) plus a vaccine was, by far, the most efficient and cost-effective treatment option. Both incidence and prevalence were significantly impacted and the WHO goal of 90% incidence reduction was achieved in the most efficient way (Vaccine). Even if the vaccine developed was not 100% effective in achieving sterilized immunity (but dramatically reduced the amount of viral load in the blood) it would still greatly reduce the ability for HCV to be transmitted to others. Our study focused on PWID population scenario as these specialty groups while a small percentage represent a higher level of infection, reinfection and transmission (Sci Transl Med). A vaccine which reduces viral load is also important for other specialty groups like healthcare workers. They are exposed to risk frequently and in some cases may not even be aware of the risk in a low-risk, routine environment like a computerized tomography (CT) scan. The risk factors are elevated because people (especially with chronic) HCV are typically asymptomatic. Another major challenge is the vast majority of HCV cases worldwide have not been diagnosed and people are unaware they are infected, much less infecting others. This puts groups typically at low risk in the broader population at a higher risk for infection. This can be especially problematic for healthcare workers or other individuals exposed to even the smallest amount of infected blood (PLoS One). A vaccine that was not a fully sterilizing vaccine but simply reduced the viral load, would greatly reduce the chances of “unknown” infections in low-risk environments as well as known high-risk populations such as PWID or victims of the opioid crisis. This is a critical contribution to the strategy of HCV elimination. These special populations can also present challenges in designing HCV vaccine trials. Through the use of modelling we are currently exploring how to optimize vaccine trial design for PWID and the challenges associated with this group. The quest for controlled human infection (CHI) models to accelerated HCV vaccine development The development of a controlled human infection (CHI) model for the hepatitis C virus (HCV), is considered essential for advancing vaccine research. The design of a CHI model requires careful consideration of the key elements including viral inoculum size, viral clearance rates, and timing of blood sampling intervals for immunological evaluations. Those elements must be fully understood for further development of a final study protocol. Analyzing early viral-host kinetics immediately after time of infection and developing theoretical modeling tools are important aspects for addressing the fore-mentioned key elements to successfully design HCV vaccine trials in the CHI model. A two-step clinical trial in CHI has been recently proposed, with the first step to define viral inoculum and establish viral-host kinetic picture in the absence of any vaccination. Existing chimeric mice with humanized livers that lack of adaptive immune response has the potential to serve as an appropriate preclinical tool to studying early HCV-host interactions. Dahari Lab is focused in developing theoretical models to evaluate and provide insights into the interplay between HCV and host immune response for the design protocols of CHI model studies. This approach aims to replicate the early stages of acute HCV infection, drawing from historical data and mathematical modeling on acute HCV infections in chimpanzees, and is a promising step towards the much-needed HCV vaccine. It is still under discussions not actually happening thus far HCV Translational Science Solving Complex Problems Through a Multidisciplinary Approach At Dahari Lab, we believe solving complex problems is best achieved through a multidisciplinary approach. Our research often includes theoretical (modeling), experimental (cells and animal models) and clinical (patient-based) information to answer research questions. Prof. Susan Uprichard (who participated in the development of the first robust cell culture-based HCV infection system) and Harel Dahari have co-founded a Program for Experimental and Theoretical Modeling (PETM) at Stritch School of Medicine, to promote the interdisciplinary integration of mathematical modeling and experimental biology. Our translational research is undertaken with Prof. Scott Cotler (Director, Division of Hepatology) and partnerships with clinicians from the U.S. and abroad. It is through this research and partnerships that we apply our knowledge from basic biology and clinical trials to techniques and tools designed to improve health outcomes. Overall, the research undertaken often becomes the building blocks for other areas of research. This “Science for the sake of Science” is the first step in any interdisciplinary research. It forms the backbone that leads to work and discoveries that benefit people. This science can also guide or create a check and balance for organizations like the FDA, NIH or pharmaceutical companies. Not every experiment or clinical trial yields a positive result, but it continues to strengthen the foundational knowledge of the scientific community Translational Science Used in Promising Results for Transplant Recipients A compelling example of our interdisciplinary and translational research is the research by Prof. Uprichard and colleagues which revealed that HCV cell-to-cell spread is a critical antiviral drug target and that the FDA-approved drug ezetimibe (EZE; trade name Zetia®) blocks HCV entry and cell-to-cell spread (Nature Medicine). This same foundational knowledge has been applied in a new way with significant results while exploring lung and kidney transplants infected with HCV. Dahari Lab along with Prof. Jordan Feld and colleagues (Canadian cohort) showed that patients can receive a short combo of EZE + direct-acting antiviral (DAA) therapy to block the development of HCV infection once infected transplant is received. This has significant implications for the availability of organs, patient risk and care, as well as DAA cost (Lancet Gastro and Hepatol). This comes at a time when HCV infection and mortality rates in younger populations are on the rise due to the ongoing opioid crisis (CDC). Better Understanding of the Role of the Liver in HCV Clearance through Modeling While the liver, specifically hepatocytes, are widely accepted as the main source for HCV production, the role of the liver/hepatocytes in the clearance of circulating HCV remains largely unknown. Through kinetic and theoretical modeling (in silico) results from both liver transplantation (LT) cases (in vivo) and in cell culture experiments (in vitro) we show that the liver (and hepatocytes) plays a major role in clearing HCV from blood circulation (eLife). To the best of our knowledge, this study is the first one to investigate very detailed HCV kinetics during the absence of the liver and immediately after graft reperfusion. Our study, along with in vitro experiments suggests a role for hepatocytes in the clearance of the virus, a phenomenon which may be limited to hepatotropic viruses. The finding that the liver plays a key role in clearing HCV from the circulation has implications for clinical best practices regarding transplantation and antiviral treatment. For LT, the fact that viral levels remain at a steady state during the absence of the liver phase or anhepatic phase (i.e., the time period after patient liver is removed until the new liver is engrafted), reinforces the need of achieving viral clearance* prior to the anhepatic phase to prevent infection of the liver graft by circulating HCV in blood and avoid antiviral treatment after LT. * Viral clearance is defined as less than 1 copy of the virus genome in the blood stream. A patient is deemed “cured” (also referred to as a sustained virological response, SVR) if six months after the end of antiviral treatment or after LT the virus is not detected in the blood. Modeling cell-to-cell spread of hepatitis C viral (HCV) infection in vitro HCV has two modes of transmission. It enters and spread via the cell-free mode of transmission circulating throughout the host. Once infection is established in the host via cell-free transmission, it can also spread via cell-to-cell. In this case, an infected cell can transmit the virus to adjacent cells. While much is understood about HCV entry and infection via cell-free mode of transmission, the role of HCV cell-to-cell spread in the liver is not as well known. In our research, in collaboration with Dr. Frederik Graw, we set out to quantify cell-to-cell transmission and assess the impact of cellular factors, viral factors, and antivirals (J Virology, Viruses, BioRxiv). Our ongoing research using agent-based modeling (ABM) has greatly enhanced our understanding of this phenomenon. The ABM developed for the study more closely mirrors the complex biological system and cellular functions. The model allowed us to better approximate how the virus spreads in the liver. Due to its complexity, study of HCV in the liver is less common, relying typically, on samples found in the blood. This interactive model (Anylogic) shows what happens when direct viral infection is removed as a variable and only cell-to-cell transmission is allowed. As a result, we are able to study not only the specific mechanism by which the drugs block cell-to-cell spread, but more importantly, measure and quantify their efficacy. Our study included the use of EZE, a cell-to-cell inhibitor, which was also used successfully in blocking HCV infection in transplant patients (The Lancet Gastroenterology & Hepatology). An increased understanding of cell-to cell transmission is important because it is seen a major contributor to viral persistence including developing resistance to therapies. In the case of inhibitor drug therapies or the patient’s own antibodies which block the virus from spreading, the virus can continue to spread via cell-to-cell. Conversely, armed with this knowledge, it is possible to develop more effective anti-virals and treatments. Limitations, Advancements and Free Open Source Numerical Methods for Parameter Estimation of HCV Kinetic Models" Dahari Lab’s commitment to advances in HCV treatment thru viral kinetic models requires constant vigilance in the area of advanced computational and mathematical methods. Modeling is not without its limitations and we are committed to pushing the boundaries in this field. Equally important is the promoting and access of these models for others to build on in their own research. We believe in an open source mindset where applicable, ensuring the greatest number of researchers world-wide have access to advance their own work. In 2016, a partnership with Prof. Danny Barash and colleagues set in motion a series of papers that exemplify this commitment. In 2017 a robust and efficient numerical method was presented for the solution of HCV multiscale models of partial differential equations (PDE). Based on this method, a simulator for PDE with a graphical user interface (GUI) was developed (Frontiers in Applied Mathematics and Statistics). The following year the properties of the numerical solution were investigated and fine-tuned in light of advances in numerical methods (Mathematical Biosciences). The GUI was also given enhancements improving its utility (AIP Conference Proceedings). A 2019 paper followed up with a unique procedure developed to perform parameter estimation directly from the model equations (Bulletin of Mathematical Biology). This was further developed and improved in 2020 (Mathematics Special Issue Mathematical Modelling in Biomedicine). The compound effect of this research has resulted in viral kinetic models that can be calibrated efficiently for more complicated cases. The model simulators also allow for associated quantities to be known or predicted like viral trajectory over time and patient treatment time-to-cure (Journal of Infectious Diseases; Antiviral Research). Click here to access our free (HCV) viral kinetic model simulators (standard or multiscale).

  • Research | DahariLab

    Research About Us In Dahari lab, Division of Hepatology , we conduct research at the intersection of experimental, clinical and theoretical biology with an emphasis on viral infection dynamics and treatment response with a particular focus on hepatitis viruses such as HCV, HEV, HBV and HDV. We apply our interdisciplinary approach across both in vitro and in vivo experimental systems as well as population and patient clinical data with the aim to find and optimize interventions and therapeutics that may ultimately prevent and/or cure these infections. Our collaborators perform viral infection experiments in cell cultures and small animal models that provide the basis for developing mathematical models at a molecular level. We also collaborate closely with public health researchers in Chicago and clinicians in our Division of Hepatology as well as many other clinicians in the United States and abroad who provide kinetic data from patients during infection and treatment. Our data-driven modeling approach helps provide new insights into the dynamics of viral-host-drug interactions during infection and treatment from the molecular to the population level. See Publications HBV HDV HCV Other viruses

  • Other viruses | DahariLab

    Other Viruses Dahari Lab has always had a flexible approach to research and solving problems. We work globally with a relentless curiosity to produce results that solve crucial problems related to the hepatitis virus as well as contribute to the larger body of basic science. Often times this research will be used in the fight against other diseases, sometimes immediately or years later. These break throughs can happen at the intersection of public policy and science to solve a specific problem or through purely academic investigation which is central to scientific research. Ebola, Covid-19, Theiler virus (TMEV), HIV and HEV are examples of lab research with global partners that contributes to the ongoing research to manage these critical health issues. Through open investigation using data modeling and involving multidisciplinary partners, these advances are possible. Research Topics Modeling Challenges of Ebola Virus - Host Dynamics during Infection and Treatment Click to read artcle Modeling the acute and chronic phases of Theiler murine encephalomyelitis virus infection Click to read article Epstein–Barr Virus (EBV) Epithelial Associated Malignancies: Exploring Pathologies and Current Treatments Click to read article Mathematical modeling of viral kinetics under immune control during primary HIV-1 infection Click to read article Plasma hepatitis E virus kinetics in solid organ transplant patients receiving ribavirin Click to read article

  • HDV | DahariLab

    HDV Translational Science Globally, over 40 million people are infected with the Hepatitis Delta virus (HDV). In the US, there is an alarming trend in the rise of infections. Hepatitis D remains a serious challenge for three reasons. First, there is no FDA approved therapy, and the current treatment with interferon-alpha has a very low success rate, twenty five percent. It is the most aggressive form of viral hepatitis and results in accelerated liver-related deaths and hepatocellular carcinoma (a common form of liver cancer). Lastly, there are limited cell-culture and animal models to study the virus in order to test new antivirals.HDV research is still in the beginning stages and the viral dynamics are unique. It is a “satellite” virus and is only infectious in the presence of the hepatitis B virus (HBV). Infection can occur in two ways: coinfection with both HDV and HBV at the same time or the HDV superinfection of an already HBV-infected individual. It is not known why HDV superinfection (compared to co-infection) leads to a higher risk of chronic HDV infection and hepatitis. There is no vaccine for HDV, but it can be theoretically controlled as a result of the success of global HBV vaccinations.Dahari Lab works across disciplines with computational modelers, virologists, clinicians, mouse-model experts and pharmaceutical companies on advancements in treatment. Our focus is on the discovery of HDV treatment response dynamics, the optimization of HDV therapy, and the evaluation of anti-HDV mode of actions of new drugs. Research can be divided across the study of human patients, mouse models and cell cultures. Data collected from all three types of research contribute to the foundational knowledge that is essential in understanding and treating HDV. Clinical (patient) data increases our understanding of the host/virus interplay, especially with new treatments. Mouse models offer the opportunity to study acute HDV because the moment of infection can be controlled (clinical data is mostly from chronic infections.) At the cellular level, these models allow for research within the liver cells directly.Access to data from all three sources, clinical (human), mouse model, and molecular (cellular), offer richer data to develop more sophisticated multicompartmental models. The ability to isolate the virus dynamics and describe in detail the interplay at the host (human), organ (liver) and cellular level is the key to unlocking effective treatments and eventual cure. Research Topics Interferon-alpha (IFN-α): Effect of Interferon-alpha Monotherapy on Hepatitis D Virus (HDV) Currently there are no FDA approved treatments and the prevalent treatment using Interferon-alpha, however patients often relapse even after years of consistent treatment. Monotherapies are often not as effective as multi-therapy treatments, but they provide useful building blocks for foundational knowledge. IFN-α is an example of a less than optimal treatment that has formed the spine of ongoing research. In the spirit of developing a better understanding of the viral kinetics of HDV, we used mathematical modeling (Hepatology), which was successful in developing optimal treatment strategies for patients with hepatitis C virus. This study provided the first detailed kinetic analysis of HDV during pegylated IFN-α therapy and provides new information about HDV infection including the HDV-host dynamics. IFN’s mode of action and effectiveness were also evaluated and contribute to basic science in viral dynamics in general and HDV specifically. Multi-Therapy LIFT hepatitis (HDV) Study: A Phase 2 Study of Lonafarnib, Ritonavir and Peginterferon Lambda Based on the successful indications from two previous monotherapy studies using LNF-RTV and Interferon Lambda, this multi-therapy this multi-therapy study was developed for a first-in-humans clinical trial for patients with chronic HDV. This combination of monotherapies into one treatment regimen confirmed the treatment was safe and tolerable for up to 6 months. Not only was it well-tolerated, but there was a sustained ant-HDV response recorded. The research ends with a question as to whether an increased duration of therapy might lead to increased response rates. Our research is ongoing to characterize and analyze the kinetics through mathematical modeling to better understand the viral-host dynamics. This Multi-Therapy LIFT hepatitis (HDV) study illustrates the direct benefits and impact of research where the outcome is new data or insights which is useful for developing new studies that could lead to new basic science information or a treatment/solution Modeling Hepatitis Delta Virus (HDV) Dynamics During Ritonavir (RTV) Boosted Lonafarnib (LNF) Treatment–The LOWR HDV-3 Study In further study of treatment with Lonafarnib combined with Ritonavir, data collected from a clinical trial was used to investigate viral kinetics and provide insights into HDV-HBsAg-host dynamics during LNF+RTV treatment. The data model initially predicted that a LNF monotherapy dose of 610 mg bid would achieve 99% efficacy [Hepatology Comm, 2017]. Given the maximum LNF tolerated dose was 200 mg bid, the clinical trial would need to be adapted to patient-real-world experience. The addition of RTV allows for slower metabolization of the LNF, resulting in lower dosage and higher efficacy. In the LOWR HDV-3 study combining LNF 100 mg bid with RTV was investigated and exceeded the predicted 99% efficacy concentration [AALSD oral abstract #38]. It was associated with dramatic HDV viral load declines and better tolerability than higher doses of LNF monotherapy. The model was also able to reproduce the observed viral, HBsAg and ALT kinetics in each patient and provide insights into viral-host-drug dynamics. The benefit to patients was real-time modeling of viral kinetics which can be used to individualize duration of therapy. In general, this type of modeling can empower patients to participate in shared decision-making regarding length of treatment. Lonafarnib (LNF): Oral prenylation inhibition with lonafarnib in chronic hepatitis D (HDV) infection This first-in-man, proof-of-concept study aimed to assess the effect of the prenylation inhibitor lonafarnib (LNF) on hepatitis D (HDV) RNA, safety, and tolerability in patients with chronic HDV. Prenylation inhibition disrupts the interaction between aspects of HDV and hepatitis B (HBV) that allow for HDV to be secreted from infected cells. Clinical research with a small sample of patients, in collaboration with Theo Heller and Christopher Koh (NIH, USA), Jeffrey Glen (Stanford) and Eiger Biopharmaceuticals, yielded results strong enough to warrant further research in this area. [Lancet, 2015] The use of LNF reduced the viral load significantly faster than mono-therapies using interferon-based treatments. For the first time, we were able to estimate LNF high efficacy in blocking HDV production and estimate the half-life of HDV in the blood through mathematical modeling of patient data. LNF was effective in all the patients in the small sample, whereas interferon-based therapies often have a percentage of patients that do not see results. A significant research benefit of LNF is that it targets only HDV, while interferon-based therapies are more general, targeting both HDV and HBV. This is a unique opportunity to better understand the interplay of HDV and HBV as well as map the mode of action. In modeling additional data sets of patients chronically infected with HDV from the research with Koh et al., it was possible to predict that a LNF monotherapy dose of 610 mg bid would achieve 99% efficacy [Hepatology Comm. 2017]. While this research did not include clinical trials involving ritonavir, it posed the question that led to actual research on the topic. Mathematical modeling of early hepatitis D virus kinetics in transgenic mice In research conducted in partnership with Ploss Lab at Princeton University, we characterized the early kinetics of HDV and provided insights into early HDV-host dynamics using mathematical modeling. The study involved data from three groups of mice (immunocompetent, immunodeficient, and transgenic*) inoculated with HDV simulating single infection and reinfection. Ongoing research is currently underway to better understand all the dynamics contributing to viral clearance rates. *Transgenically expressing human NTCP (NRG-hNTCP) the receptor for HBV/HDV entry. Mathematical modeling suggests that entry-inhibitor bulevirtide (BLV) may interfere with hepatitis D virus clearance from circulation While in some patient data modeled by Shekhtman et al 2022, BLV (an entry HDV blocker) experienced a decline consistent with its known mode of action, a second effect was also observed. Under treatment with BLV it was possible to observe an increase of HDV before HDV declined, suggesting BLV may also affect the liver’s ability to clear the virus. This transient HDV increase pattern was also seen in study presented by Hershkovich and Shehktman et al at the 2022 International HBV Meeting*, via analyzing and modeling a published BLV monotherapy study. *2022 International HBV meeting "Molecular Biology of hepatitis B viruses" [Paris, Sept. 18-22]

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