Academic Appointments

Honors & Awards

  • NEEMA (Epidemiologic and Economic Modeling Grant) Prevention policy modeling lab (PPML), Centers for Disease Control and Prevention (2020-2025)
  • The 2016 Stanford Cancer Institute Translational Research Grant, Stanford Cancer Institute (2016-2017)
  • Spectrum Accelerator Innovation Seed Grant, Stanford Center for Clinical and Translational Research and Education (2014-2015)
  • Takemi Fellow in International Health, Harvard School of Public Health (2011-2013)
  • Gratification for Exceptional Research, Erasmus Medical Center (2008)
  • Sheila Sherlock Fellowship, European Association for the Study of the Liver (2008)

Boards, Advisory Committees, Professional Organizations

  • Member, ICE-HBV International Coalition to Eliminate HBV (2017 - Present)
  • Member, Strategic Information and Modeling Reference Group, World Health Organization (2016 - Present)
  • Expert Panel, European Association for the Study of the Liver (EASL) (2015 - Present)
  • Expert Panel, The Asian Pacific Association for the Study of the Liver (APASL) (2015 - Present)
  • Member of the Liver Cancer Working Group, Stanford University (2014 - Present)
  • Editorial Board, World Journal of Gastroenterology (2013 - Present)
  • Member, International Society for Pharmacoeconomics and Outcomes Research (ISPOR) (2012 - Present)
  • Advisor, Burden of Disease Study Bielefeld, Germany (2010 - 2011)
  • Member of Knowledge Team, LiverDoc (2007 - Present)
  • Platform Member, European Vigilance Network for the Management of Antiviral Drug Resistance (VIRGIL) (2007 - 2008)

Service, Volunteer and Community Work

  • Global Hepatitis Report 2017, World Health Organization

    Reviewer of data and content



  • Public Health Internship (2006)


    Cape Town, South Africa

  • Research Hepatitis B, Rui Jin hospital Jia Tong University (2010)


    Shanghai, China

  • Research Hepatitis B, Ankara Medical School (2009)


    Ankara, Turkey

All Publications

  • Hepatitis delta virus infection in Turkey: A meta-analysis of prevalence. IJID regions Toy, M., Guler, B., Somay, K., Gencdal, G., Yurdaydin, C. 2024; 10: 228-234


    Objectives: Hepatitis delta virus (HDV) infection has been granted orphan disease status by the US Food and Drug Administration and the European Medicines Agency owing to its rarity and relatively limited research and treatment options. Turkey is considered an endemic country for the virus. We aimed to provide a current and updated country- and region-specific HDV infection prevalence.Methods: In this meta-analysis, we searched databases, including MEDLINE, PUBMED, EMBASE, and UlakBim (Turkish Medical Index) published between January 1, 2006, and December 31, 2022. We included blood donor studies, outpatient clinic studies that comprised patients without cirrhosis, and inpatient clinical studies that comprised patients with cirrhosis. Turkey was divided into three regions: West, Central, and East Turkey.Results: After a systematic assessment, 41 studies were included. Using a random-effects model, the estimated HDV prevalence among hepatitis B surface antigen-positive blood donors, outpatient clinic, and inpatient clinic patients were 3.37% (confidence interval [CI] 1.99-6.11), 5.05% (CI 4.00-6.23), and 29.06% (CI 10.45-51.79), respectively. The HDV prevalence among outpatient clinic patients in Western, Central, and Eastern regions were 3.38% (CI 2.47-4.44), 2.15% (CI 1.37-3.09), and 9.81% (CI 6.61-13.55), respectively.Conclusions: East Turkey continues to have a high burden of HDV. Public health efforts, such as screening, should be targeted accordingly.

    View details for DOI 10.1016/j.ijregi.2024.02.003

    View details for PubMedID 38444561

  • Psychometric Tests for Hepatitis B - A Systematic Review. Evaluation & the health professions Ispas, S., Iliescu, D., Ren, L., So, S., Toy, M. 2023: 1632787231188458


    Hepatitis B is a condition that directly affects hundreds of millions of people, who may require testing for certain psychological constructs. This systematic review presents the current state with regard to the instruments that are used for the measurement of psychological variables in relation to hepatitis B. We conducted a comprehensive search in bibliographic databases (PubMed, Embase, Scopus, Web of Science, PsycINFO, CINAHL, and the Cochrane Library), and grey literature search. We identified commonly used measures, their psychometric properties and gaps in the research. Our findings from the 38 papers included in the review indicate that while several tests have been developed to cater to hepatitis B patients, most are focused on quality of life, with few targeting other needed directions, such as stigma or attitudes to vaccination. We also show the limits in current measures and discuss potential improvements.

    View details for DOI 10.1177/01632787231188458

    View details for PubMedID 37461882

  • Hepatitis delta virus infection in Turkey: A meta analysis of prevalence Toy, M., Senturk, B., Somay, K., Gencdal, G., Yurdaydin, C. ELSEVIER. 2023: S928-S929
  • Gaps and Disparities in Chronic Hepatitis B Monitoring and Treatment in the United States, 2016-2019. Medical care Pham, T. T., Toy, M., Hutton, D., Thompson, W., Conners, E. E., Nelson, N. P., Salomon, J. A., So, S. 2023; 61 (4): 247-253


    BACKGROUND: Chronic hepatitis B (CHB) carries an increased risk of death from cirrhosis and hepatocellular carcinoma (HCC). The American Association for the Study of Liver Diseases recommends patients with CHB receive monitoring of disease activity, including ALT, hepatitis B virus (HBV) DNA, hepatitis B e-antigen (HBeAg), and liver imaging for patients who experience an increased risk for HCC. HBV antiviral therapy is recommended for patients with active hepatitis and cirrhosis.METHODS: Monitoring and treatment of adults with new CHB diagnoses were analyzed using Optum Clinformatics Data Mart Database claims data from January 1, 2016, to December 31, 2019.RESULTS: Among 5978 patients with new CHB diagnosis, only 56% with cirrhosis and 50% without cirrhosis had claims for≥1 ALT and either HBV DNA or HBeAg test, and among patients recommended for HCC surveillance, 82% with cirrhosis and 57% without cirrhosis had claims for≥1 liver imaging within 12 months of diagnosis. Although antiviral treatment is recommended for patients with cirrhosis, only 29% of patients with cirrhosis had≥1 claim for HBV antiviral therapy within 12 months of CHB diagnosis. Multivariable analysis showed patients who were male, Asian, privately insured, or had cirrhosis were more likely (P<0.05) to receive ALT and either HBV DNA or HBeAg tests and HBV antiviral therapy within 12 months of diagnosis.CONCLUSION: Many patients diagnosed with CHB are not receiving the clinical assessment and treatment recommended. A comprehensive initiative is needed to address the patient, provider, and system-related barriers to improve the clinical management of CHB.

    View details for DOI 10.1097/MLR.0000000000001825

    View details for PubMedID 36893410

  • Gaps in Prenatal Hepatitis B Screening and Management of HBsAg Positive Pregnant Persons in the U.S., 2015-2020. American journal of preventive medicine Pham, T. T., Maria, N., Cheng, V., Nguyen, B., Toy, M., Hutton, D., Conners, E. E., Nelson, N. P., Salomon, J. A., So, S. 2023


    The Advisory Committee for Immunization Practices (ACIP) recommends testing all pregnant women for hepatitis B surface antigen (HBsAg) and testing HBsAg-positive pregnant women for hepatitis B virus deoxyribonucleic acid (HBV DNA). HBsAg-positive pregnant persons are recommended by the American Association for the Study of Liver Diseases to receive regular monitoring, including alanine transaminase (ALT) and HBV DNA and antiviral therapy for active hepatitis and to prevent perinatal HBV transmission if HBV DNA level is >200,000 IU/mL.Using Optum Clinformatics Data Mart Database claims data, pregnant women who received HBsAg testing and HBsAg-positive pregnant persons who received HBV DNA and alt testing and antiviral therapy during pregnancy and after delivery during January 1, 2015-December 31, 2020 were analyzed.Among 506,794 pregnancies, 14.6% did not receive HBsAg testing. Pregnant women more likely to receive testing for HBsAg (p<0.01) were persons aged ≥20 years, were Asian, had >1 child, or received education beyond high school. Among the 0.28% (1,437) pregnant women who tested positive for hepatitis B surface antigen, 46% were Asian. The proportion of HBsAg-positive pregnant women who received HBV DNA testing during pregnancy and in the 12 months after delivery was 44.3% and 28.6%, respectively; the proportion that received HBsAg was 31.6% and 12.7%, respectively; the proportion that received ALT testing was 67.4% and 47%, respectively; and the proportion that received HBV antiviral therapy was 7% and 6.2%, respectively.This study suggests that as many as half a million (∼14%) pregnant persons who gave birth each year were not tested for HBsAg to prevent perinatal transmission. More than 50% of HBsAg-positive persons did not receive the recommended HBV-directed monitoring tests during pregnancy and after delivery.

    View details for DOI 10.1016/j.amepre.2023.01.041

    View details for PubMedID 36906494

  • Knowledge and Attitude Related to Hepatitis C among Medical Students in the Oral Direct Acting Antiviral Agents Era in Vietnam. International journal of environmental research and public health Pham, T. T., Nguyen, T. T., So, S., Hoang, T. H., Nguyen, T. T., Ngo, T. B., Nguyen, M. P., Thai, Q. H., Nguyen, N. K., Ho, T. Q., Tran, Q. P., Mai, T. S., Toy, M., Pham, M. K. 2022; 19 (19)


    BACKGROUND: Medical students play important frontline roles in the prevention, early detection, and treatment of hepatitis C. This study investigated knowledge and attitudes toward hepatitis C among 5th- and 6th-year medical students and possible associated factors.METHODS: A cross-sectional survey was conducted among 2000 students from eight medical universities using a self-administered structured questionnaire.RESULTS: The mean knowledge and attitude scores for hepatitis C were 20.1 ± 4.0 (out of 26) and 10.6 ± 2.9 (out of 20), respectively. Approximately, three-quarters (74.4%) of the participants had a good knowledge score, but only a small proportion (3.1%) obtained a good attitude score. Although the participants had fairly high knowledge about the causes, consequences, and transmission routes of hepatitis C, there were important gaps in their knowledge about hepatitis C screening and treatment. In multivariate analysis, female students, 5th-year students, and students from the central provinces had significantly higher knowledge and attitude scores. There was a low positive correlation between knowledge and attitude scores.CONCLUSION: This study points out the need to update the medical training curriculum to improve the knowledge and attitude of students about hepatitis C infection.

    View details for DOI 10.3390/ijerph191912298

    View details for PubMedID 36231600

  • Costs and health impact of delayed implementation of a national hepatitis B treatment program in China. Journal of global health Toy, M., Hutton, D., Jia, J., So, S. 2022; 12: 04043


    Background: Hepatitis B virus (HBV) infection is a leading public health problem in China. COVID-19 pandemic has interrupted the delivery of health care interventions worldwide, including HBV infection control.Methods: In this study, we used a Markov model to quantify the costs and population health impact of HBV treatment in China for the following scenarios: 1) current practice with only 17% of treatment eligible HBV infected adults receiving antiviral treatment; 2) reaching the World Health Organization (WHO) treatment target of 80% by 2030 with a steady increase in treatment rate beginning in 2022; and 3) the effect of a 1-5-year delay in meeting the 2030 WHO treatment target. A one-way as well as a probabilistic sensitivity analysis were conducted.Results: Without increasing antiviral treatment for treatment eligible HBV infected adults, the life-time health care costs for the estimated 89.2 million adults living with HBV in China is US$1305 billion and 10.8 million (12%) will die from HBV-related liver disease. Increasing treatment to achieve the WHO 80% target by 2030 would save US$472 billion and prevent 3.3 million HBV-related deaths. We estimated that a 1-year delay beyond 2030 in reaching the WHO 80% treatment target would likely lead to US$55 billion increase in future health care costs, and an additional 334000 future deaths from HBV-related liver disease or cancer.Conclusions: Reaching the WHO 2030 with minimal delays would have an immense health and economic benefit. Implementing a national treatment program for HBV in China should be a key priority for policymakers.

    View details for DOI 10.7189/jogh.12.04043

    View details for PubMedID 35796158

  • Cost-Effectiveness of Hepatitis B Testing and Vaccination of Adults Seeking Care for Sexually Transmitted Infections. Sexually transmitted diseases Hutton, D., Toy, M., Salomon, J. A., Conners, E. E., Nelson, N. P., Harris, A. M., So, S. 2022


    BACKGROUND: The estimated number of people living with hepatitis B virus (HBV) infection acquired through sexual transmission was 103,000 in 2018, with an estimated incidence of 8,300 new cases per year. While hepatitis B (HepB) vaccination is recommended by the Advisory Committee for Immunization Practices for persons seeking evaluation and treatment for sexually transmitted infections (STI), pre-vaccination testing is not yet recommended. Screening may link persons with chronic hepatitis B (CHB) to care and reduce unnecessary vaccination.METHODS: We used a Markov model to calculate the health impact, and cost-effectiveness of one-time HBV testing combined with the first dose of the hepatitis B vaccine for adults seeking care for STI. We ran a lifetime, societal perspective analysis for a hypothetical population of 100,000 ages 18-69 years. The disease progression estimates were taken from recent cohort studies and meta-analyses. In the US, an intervention that costs less than $100,000 per quality adjusted life year (QALY) is generally considered cost-effective. The strategies that were compared were: 1) vaccination without HBV screening, 2) vaccination and HBsAg screening, 3) vaccination and screening with HBsAg and anti-HBs, and 4) vaccination and screening with HBsAg, anti-HBs and anti-HBc. Data were obtained from Centers for Medicare and Medicaid services reimbursement, the CDC vaccine price list, and additional cost-effectiveness literature.RESULTS: Compared with current recommendations, the addition of one-time HBV testing is cost saving and would prevent an additional 138 cases of cirrhosis, 47 cases of decompensated cirrhosis, 90 cases of hepatocellular carcinoma, 33 liver transplants, and 163 HBV-related deaths, and gain 2185 QALYs, per 100,000 adults screened. Screening with the 3-tests panel would save $41.6-$42.7 million /100,000 adults tested compared with $41.5-$42.5 million for the 2-tests panel and $40.2-$40.3 million for HBsAg alone.CONCLUSIONS: One-time HBV pre-vaccination testing in addition to HepB vaccination for unvaccinated adults seeking care for STI would save lives, prevent new infections and unnecessary vaccination, and is cost saving.

    View details for DOI 10.1097/OLQ.0000000000001632

    View details for PubMedID 35312661

  • Letter to the Editor: Importance of Universal Screening for Chronic Hepatitis B Infection in Adults in the United States. Hepatology (Baltimore, Md.) Cohen, C., Moraras, K., Jackson, M., Kamischke, M., Gish, R. G., Brosgart, C. L., Toy, M., Hutton, D., Block, T. M., Wang, S., So, S. 1800

    View details for DOI 10.1002/hep.32304

    View details for PubMedID 34951931

  • The Price Tag of a Potential Cure for Chronic Hepatitis B Infection: A Cost Threshold Analysis for USA, China, and Australia. Liver international : official journal of the International Association for the Study of the Liver Toy, M., Hutton, D., McCulloch, K., Romero, N., Revill, P. A., Penicaud, M., So, S., Cowie, B. C. 2021


    BACKGROUND & AIMS: We aim to capture the economic impact of a potential cure for chronic hepatitis B infection (CHB) in three countries (USA, China, and Australia) with different health systems and epidemics to estimate the threshold drug prices below which a CHB cure would be cost-saving and/or highly cost-effective.METHODS: We simulated patients' hepatitis B progression, under three scenarios: current long-term suppressive antiviral therapy, functional cure defined as sustained undetectable HBsAg and HBV DNA, and partial cure defined as sustained undetectable HBV DNA only after a finite, 48-week treatment.RESULTS: Compared with current long-term antiviral therapy, a 30% effective functional cure among patients with and without cirrhosis in the USA, China and Australia would yield 17.50, 17.32 and 20.42 QALYs per patient, and 20.61, 20.42 and 20.62 QALYs, respectively. In financial terms, for CHB patients with and without cirrhosis, this would be cost-saving at a one-time treatment cost under US$11,944 and US$6,694 respectively in the USA, US$1,744 and US$1,001 in China, and US$12,063 and US$10,983 in Australia.CONCLUSION: We show that in purely economic tems, a CHB cure will be highly cost-effective even if effective in only 30% of treated patients. The threshold price for cure is largely determined by the current antiviral drug costs, since it will replace a daily antiviral pill that is inexpensive and effective, although not curative. The likely need for combination therapies to achieve cure will also present cost challenges. While cost-effectivenss is important, it cannot be the only consideration, as cure will provide many benefits additional to reduced liver diease and HCC, including eliminating the need for a long term daily pill and reducing stigma often associated with chronic viral infection.

    View details for DOI 10.1111/liv.15027

    View details for PubMedID 34328697

  • Cost-Effectiveness of One-Time Universal Screening for Chronic Hepatitis B Infection in Adults in the United States. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Toy, M., Hutton, D., Harris, A. M., Nelson, N., Salomon, J. A., So, S. 2021


    BACKGROUND: An estimated 862,000 to 2.4 million people have chronic hepatitis B infection (CHB). Left undiagnosed and untreated CHB increases risk of death from liver cirrhosis or liver cancer. Hepatitis B screening is recommended for pregnant women and populations with increased CHB risk, but diagnosis rates remain low with only 33% of people with CHB aware of their infection.. This study aimed to assess the cost-effectiveness of universal adult screening for CHB.METHODS: We used a Markov model to calculate the costs, population health impact and cost-effectiveness of one-time universal screening and CHB monitoring and treatment compared to current practice. Sensitivity analysis was performed on model parameters to identify thresholds for cost-savings or cost-effectiveness based on willinness-to-pay of $50,000/QALY . The analysis assumed testing would be performed during routine healthcare visits, and generic tenofovir or entecavir would be dispensed for treatment. Testing costs were based on Medicare reimbursement rates.RESULTS: At an estimated 0.24% prevalence of undiagnosed CHB, universal HBsAg screening in adults 18-69 years old is cost-saving compared with current practice if antiviral treatment drug costs remain below $894 per year. Compared with current practice, universal screening would avert an additional 7.4 cases of compensated cirrhosis, 3.3 cases of decompensated cirrhosis, 5.5 cases of hepatocellular carcinoma, 1.9 liver transplants, and 10.3 HBV related deaths at a savings of $263,000 per 100,000 adults screened.CONCLUSION: Universal HBsAg screening of adults in the US general population for CHB is cost-effective and likely cost-saving compared to current CHB screening recommendations.

    View details for DOI 10.1093/cid/ciab405

    View details for PubMedID 33956937

  • Cost-Effectiveness of Testing and Treatment for Hepatitis B Virus and Hepatitis C Virus Infections: An Analysis by Scenarios, Regions, and Income. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research Tordrup, D., Hutin, Y., Stenberg, K., Lauer, J. A., Hutton, D. W., Toy, M., Scott, N., Chhatwal, J., Ball, A. 2020; 23 (12): 1552–60


    OBJECTIVES: Testing and treatment for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are highly effective, high-impact interventions. This article aims to estimate the cost-effectiveness of scaling up these interventions by scenarios, regions, and income groups.METHODS: We modeled costs and impacts of hepatitis elimination in 67 low- and middle-income countries from 2016 to 2030. Costs included testing and treatment commodities, healthcare consultations, and future savings from cirrhosis and hepatocellular carcinomas averted. We modeled disease progression to estimate disability-adjusted life-years (DALYs) averted. We estimated incremental cost-effectiveness ratios (ICERs) by regions and World Bank income groups, according to 3 scenarios: flatline (status quo), progress (testing/treatment according to World Health Organization guidelines), and ambitious (elimination).RESULTS: Compared with no action, current levels of testing and treatment had an ICER of $807/DALY for HBV and -$62/DALY (cost-saving) for HCV. Scaling up to progress scenario, both interventions had ICERs less than the average gross domestic product/capita of countries (HBV: $532/DALY; HCV: $613/DALY). Scaling up from flatline to elimination led to higher ICERs across countries (HBV: $927/DALY; HCV: $2528/DALY, respectively) that remained lower than the average gross domestic product/capita. Sensitivity analysis indicated discount rates and commodity costs were main factors driving results.CONCLUSIONS: Scaling up testing and treatment for HBV and HCV infection as per World Health Organization guidelines is a cost-effective intervention. Elimination leads to a much larger impact though ICERs are higher. Price reduction strategies are needed to achieve elimination given the substantial budget impact at current commodity prices.

    View details for DOI 10.1016/j.jval.2020.06.015

    View details for PubMedID 33248510

  • The case for simplifying and using absolute targets for viral hepatitis elimination goals JOURNAL OF VIRAL HEPATITIS Razavi, H., Blach, S., Razavi-Shearers, D., Abaalkhail, F., Abbas, Z., Abdallah, A., Ferreira, P., Abu Raddad, L., Adda, D., Agarwal, K., Aghemo, A., Ahmed, A., Al-Busafi, S. A., Al-hamoudi, W., Al-Kaabi, S., Al-Romaihi, H., Aljarallah, B., AlNaamani, K., Alqahtani, S., Alswat, K., Altraif, I., Asselah, T., Bacon, B., Bessone, F., Bizri, A., Block, T., Bonino, F., BranclaoMello, C., Browny, K., Bruggmann, P., Brunetto, M., Buti, M., Cabezas, J., Calleja, J., Batanjer, E., Chan, H., Chang, H., Chen, C., Christensen, P., Chuang, W., Cisneros, L., Cohen, C., Colombo, M., Conway, B., Cooper, C., Craxi, A., Crespo, J., Croes, E., Cryer, D., de Barros, F., Derbala, M., Dillon, J., Doss, W., Dou, X., Doyle, J., Duberg, A., Dugan, E., Dunn, R., Dusheiko, G., El Khayat, H., EI-Sayed, M. H., Eshraghian, A., Esmat, G., Mur, R., Ezzat, S., Falconer, K., Fassio, E., Ferrinho, P., Flamm, S., Flisiak, R., Foster, G., Fung, J., Garcia-Samaniego, J., Gish, R. G., Goncales, F., Halota, W., Hamoudi, W., Hassany, M., Hatzakis, A., Hay, S., Himatt, S., Hoepelman, I. M., Hsu, Y., Hui, Y., Hunyady, B., Jacobson, I., Janjua, N., Janssen, H., Jarcuska, P., Kabagambe, K., Kanto, T., Kao, J., Kaymakoglu, S., Kershenobich, D., Khamis, F., Kim, D., Kim, Y., Kondili, L. A., KottiliI, S., Kramvis, A., Kugelmas, M., Kurosaki, M., Lacombe, K., Lagging, M., Lao, W., Lavanchy, D., Lazarus, J., Lee, A., Lee, S. S., Levyl, M., Liakina, V., Lim, Y., Liu, S., Maddrey, W., Malekzade, R., Marinho, R., Mathur, P., Maticic, M., Mendes Correa, M., Mera, J., Merat, S., Mogawer, S., Mohamed, R., Muellhaupti, B., Muljono, D., Mostafa, I., Nahum, M., Nawaz, A., Negro, F., Ninburg, M., Ning, Q., Ntiri-Reid, B., Nymadawa, P., Oevrehus, A., Ormeci, N., Orrego, M., Osman, A., Oyunsuren, T., Pant, C., Papaevangelou, V., Papatheodoridis, G., Popping, S., Prasad, P., Prithiviputh, R., Qureshi, H., Ramji, A., Razavi-Shearer, K., Reddy, R., Remak, W., Richter, C., Ridruejo, E., Robaeys, G., Robert, S., Roberts, L., Roudot-Thoraval, F., Saab, S., Said, S., Salamat, A., Sanai, F., Sanchez-Avila, J., Schiff, E., Schinazi, R., Sebastiani, G., Seguin-Devaux, C., Shanmugam, R. P., Sharara, A., Shilton, S., Shouval, D., Sievert, W., Simonova, M., Sohrabpour, A., Sonderup, M., Soza, A., Spearman, C., Steinfurth, N., Sulkowski, M., Tan, S., Tanaka, J., Tashi, D., Thein, H., Thompson, P., Tolmane, I., Toy, M., Valantinas, J., Van de Vijver, D., Velez-Moller, P., Vince, A., Waked, I., Wang, S., Wedemeyer, H., Wong, V., Xie, Q., Yamada, S., Yang, H., Yesmembetov, K., Yilmaz, Y., Younossi, Z., Yu, M., Yuen, M., Yurdaydin, C., Yusuf, A., Zekry, A., Zeuzem, S. 2020


    The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries' progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100 000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100 000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.

    View details for DOI 10.1111/jvh.13412

    View details for Web of Science ID 000584509000001

    View details for PubMedID 32979881

  • Hepatitis Delta Virus Epidemiology in the Industrialized World. AIDS reviews Toy, M., Ahishali, E., Yurdaydin, C. 2020; 23 (3)


    Within the hepatitis virus landscape, one incomplete virus, the hepatitis delta virus (HDV), appears to differ from hepatitis B and C viruses in the context as it still may not infrequently lead to complications of chronic liver disease and continues to be associated with significant liver-related mortality even when patients have received available treatment for it. Breakthrough therapies are so far lacking for HDV-infected patients and treatment has not changed since the discovery of HDV in 1977 and consists mainly of interferons. While there was little interest on the global epidemiology of HDV until recently, this has changed in the past 2 years and we are currently observing a stream of papers on the global epidemiology of HDV and commentaries about why prevalence estimates appear to differ so dramatically. This may be related to the fact that reliable data are not available for most of the countries. However, in the industrialized world, data on the epidemiology of HDV are expected to be of better overall quality. Hence, this review was undertaken to provide a detailed overview on the epidemiology of HDV infection in industrialized countries using data from representative larger countries. In industrialized countries, with maybe the exception of China, HDV infection is a disease of high-risk groups. Migrant groups and people who inject drugs are the most encountered high-risk groups. This review summarizes the dynamics of their contribution to the HDV epidemiology in industrialized countries of the west and the east.

    View details for DOI 10.24875/AIDSRev.20000056

    View details for PubMedID 33104688

  • Hepatitis B cure: modeling the economics of a potential cost of a cure. Current opinion in HIV and AIDS Toy, M., So, S., Hutton, D. W. 2020


    PURPOSE OF REVIEW: The cure for hepatitis C virus infection has raised hope for a potential hepatitis B virus (HBV) cure, but the high price tag has led to serious questions about the affordability, and thus to access for all. This review discusses cost-effectiveness models, affordability, and access to a potential new cure for chronic HBV infection.RECENT FINDINGS: A cure does not yet exist for HBV, but the antiviral treatments that are currently available help slow down the progression of disease. There is limited research in the area of cost-effectiveness and economic analysis comparing a potential cure. Our preliminary findings from modeling and economic threshold analysis show that cure could be potentially cost-effective or cost-saving. Governments can possibly use the results of economic models for price negotiations.SUMMARY: The highest burden of the HBV infection is in low and middle-income countries. Given that the cost of current treatment has dropped dramatically in recent years as the first line treatments have come off patent, the price for a HBV cure needs to be reasonable and affordable to all people.

    View details for DOI 10.1097/COH.0000000000000617

    View details for PubMedID 32209813

  • Causes and trends in liver disease and hepatocellular carcinoma among men and women who received liver transplants in the U.S., 2010-2019. PloS one Wang, S. n., Toy, M. n., Hang Pham, T. T., So, S. n. 2020; 15 (9): e0239393


    The national Organ Procurement and Transplant Network (OPTN) reported the major indication for liver transplants in 2018 was for other/unknown causes. This study was undertaken to examine all causes and trends in liver disease and hepatocellular carcinoma (HCC) among adults who received liver transplants in the past 10 years.A national cohort study of all adults who received liver transplants from Jan 1, 2010 to Dec 31, 2019 recorded in the OPTN STAR database analyzed by etiology of liver disease and HCC, and gender.Adult liver transplants increased from 5,731 in 2010 to 8,345 in 2019 (45.6% increase). Between 2010 and 2014, liver disease and HCC associated with hepatitis C (HCV) was the major cause for liver transplantation. Proportion of liver transplants for HCV associated liver disease and HCC has since decreased to 18.7% in 2019 compared with 44.5% in 2010 [25.8%, (95% CI 24.3% to 27.3%), p<0.001], while liver transplants for liver disease and HCC associated with alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) increased from 12.7% to 28.8% [16.1%, (95% CI 14.8% to 17.4%), p<0.001], and from 9.1% to 21.5% [12.4%, (95% CI 11.2% to 13.5%), p<0.001], respectively. When all causes of liver disease were examined, only 1.7% of liver transplants had unspecified causes. The five major causes of liver disease and HCC among men receiving liver transplants in 2019 were ALD (33.1%), HCV (21.9%), NAFLD (18.5%), cholestatic liver disease (5.7%) and hepatitis B (4.9%), while the major causes among women were NAFLD (26.8%), ALD (21.1%), HCV (13.1%), cholestatic liver disease (11.1%), and autoimmune liver disease (5.6%).Our study found NAFLD in 2017 in women and ALD in 2019 in men have surpassed HCV as the leading causes of liver disease and HCC among adults receiving liver transplants.

    View details for DOI 10.1371/journal.pone.0239393

    View details for PubMedID 32946502

  • Additional resource needs for viral hepatitis elimination through universal health coverage: projections in 67 low-income and middle-income countries, 2016-30. The Lancet. Global health Tordrup, D., Hutin, Y., Stenberg, K., Lauer, J. A., Hutton, D. W., Toy, M., Scott, N., Bulterys, M., Ball, A., Hirnschall, G. 2019


    BACKGROUND: The World Health Assembly calls for elimination of viral hepatitis as a public health threat by 2030 (ie, -90% incidence and -65% mortality). However, WHO's 2017 cost projections to achieve health-related Sustainable Development Goals did not include the resources needed for hepatitis testing and treatment. We aimed to estimate the incremental commodity cost of adding scaled up interventions for testing and treatment of hepatitis to WHO's investment scenarios.METHODS: We added modelled costs for implementing WHO recommended hepatitis testing and treatment to the 2017 WHO cost projections. We quantified additional requirements for diagnostic tests, medicines, health workers' time, and programme support across 67 low-income and middle-income countries, from 2016-30. A progress scenario scaled up interventions and a more ambitious scenario was modelled to reach elimination by 2030. We used 2018 best available prices of diagnostics and generic medicines. We estimated total costs and the additional investment needed over the projection of the 2016 baseline cost.FINDINGS: The 67 countries considered included 230 million people living with hepatitis B virus (HBV) and 52 million people living with hepatitis C virus (HCV; 90% and 73% of the world's total, respectively). Under the progress scenario, 3250 million people (2400 million for HBV and 850 million for HCV) would be tested and 58·2 million people (24·1 million for HBV and 34·1 million for HCV) would be treated (total additional cost US$ 27·1 billion). Under the ambitious scenario, 11 631 million people (5502 million for HBV and 6129 million for HCV) would be tested and 93·8 million people (32·2 million for HBV and 61·6 million for HCV) would be treated (total additional cost $58·7 billion), averting 4·5 million premature deaths and leading to a gain of 51·5 million healthy life-years by 2030. However, if affordable HCV medicines remained inaccessible in 13 countries where medicine patents are protected, the additional cost of the ambitious scenario would increase to $118 billion. Hepatitis elimination would account for a 1·5% increase to the WHO ambitious health-care strengthening scenario costs, avert an additional 4·6% premature deaths, and add an additional 9·6% healthy life-years from 2016-30.INTERPRETATION: Access to affordable medicines in all countries will be key to reach hepatitis elimination. This study suggests that elimination is feasible in the context of universal health coverage. It points to commodities as key determinants for the overall price tag and to options for cost reduction strategies.FUNDING: WHO, United States Centers for Disease Control and Prevention, Unitaid.

    View details for DOI 10.1016/S2214-109X(19)30272-4

    View details for PubMedID 31353061

  • Barriers to Disease Monitoring and Liver Cancer Surveillance Among Patients with Chronic Hepatitis B in the United States JOURNAL OF COMMUNITY HEALTH Ispas, S., So, S., Toy, M. 2019; 44 (3): 610–25
  • Knowledge, attitudes and practices of hepatitis B prevention and immunization of pregnant women and mothers in northern Vietnam PLOS ONE Pham, T., Le, T. X., Nguyen, D. T., Luu, C. M., Truong, B. D., Tran, P. D., Toy, M., So, S. 2019; 14 (4)
  • Economic Analyses to Inform and Support Health Policy for Chronic Hepatitis B Treatment Current Hepatology Reports Toy, M., Hutton, D. W., So, S. 2019
  • Hepatitis Delta Virus Infection: A Large Burden After All? The Journal of infectious diseases Yurdaydin, C. n., Toy, M. n. 2019

    View details for DOI 10.1093/infdis/jiz634

    View details for PubMedID 31778169

  • The Hep B Calculator: an online tool for cost-effectiveness analyses of treatment. The lancet. Gastroenterology & hepatology Toy, M. n., Hutton, D. W., Lauer, J. n., Bulterys, M. n., Hutin, Y. n., So, S. n. 2019

    View details for DOI 10.1016/S2468-1253(19)30223-7

    View details for PubMedID 31362918

  • Knowledge, attitudes and medical practice regarding hepatitis B prevention and management among healthcare workers in Northern Vietnam. PloS one Hang Pham, T. T., Le, T. X., Nguyen, D. T., Luu, C. M., Truong, B. D., Tran, P. D., Toy, M., Bozkurt, S., So, S. 2019; 14 (10): e0223733


    BACKGROUND AND AIM: Vietnam's burden of liver cancer is largely due to its high prevalence of chronic hepatitis B virus (HBV) infection. This study aimed to examine healthcare workers' (HCWs) knowledge, attitude and practices regarding HBV prevention and management.METHODS: A cross-sectional survey among health care workers working at primary and tertiary facilities in two Northern provinces in Vietnam in 2017. A standardized questionnaire was administered to randomly selected HCWs. Multivariate regression was used to identify predictors of the HBV knowledge score.RESULTS: Among the 314 participants, 75.5% did not know HBV infection at birth carries the highest risk of developing chronic infection. The median knowledge score was 25 out of 42 (59.5%). About one third (30.2%) wrongly believed that HBV can be transmitted through eating or sharing food with chronic hepatitis B patients. About 38.8% did not feel confident that the hepatitis B vaccine is safe. Only 30.1% provided correct answers to all the questions on injection safety. Up to 48.2% reported they consistently recap needles with two hands after injection, a practice that would put them at greater risk of needle stick injury. About 24.2% reported having been pricked by a needle at work within the past 12 months. More than 40% were concerned about having casual contact or sharing food with a person with chronic hepatitis B infection (CHB). In multivariate analysis, physicians scored significantly higher compared to other healthcare professionals. Having received training regarding hepatitis B within the last two years was also significantly associated with a better HBV knowledge score.CONCLUSIONS: Findings from the survey indicated an immediate need to implement an effective hepatitis B education and training program to build capacity among Vietnam's healthcare workers in hepatitis B prevention and control and to dispel hepatitis B stigma.

    View details for DOI 10.1371/journal.pone.0223733

    View details for PubMedID 31609983

  • Population Health And Economic Impacts Of Reaching Chronic Hepatitis B Diagnosis And Treatment Targets In The US. Health affairs (Project Hope) Toy, M., Hutton, D. W., So, S. 2018; 37 (7): 1033–40


    The National Academies of Sciences, Engineering, and Medicine have concluded that eliminating the public health problem of chronic hepatitis B is feasible. We examined the economic and public health impact of reaching the World Health Organization targets of having 90percent of chronic hepatitis B cases diagnosed and 80percent being treated by 2030 in the United States with an annual incremental increase in screening and treatment rates. To reach the targets by 2030 would require screening approximately 14.5million adults in at-risk populations to diagnose an estimated 870,000 undiagnosed cases and would result in substantial health gains: an increase of 16.5million quality-adjusted life-years (QALYs), and reductions in liver-related deaths of 37percent and in cases of compensated cirrhosis of 24percent, decompensated liver cirrhosis of 51percent, and liver cancer of 35percent. Achieving the targets by 2030 would be highly cost-effective at $103 per QALY and would be cost-saving if the antiviral drug price were no more than $114 per month. Achieving them by 2025 would be cost-saving and would reduce liver-related deaths by 47percent.

    View details for PubMedID 29985701

  • Racial/ethnic- and county-specific prevalence of chronic hepatitis B and its burden in California Hepatology, Medicine and Policy Toy, M., Wei, B., Virdi, T. S., Le, A., Trinh, H., Li, J., Zhang, J., Hsing, A. W., So, S. K., Nguyen, M. H. 2018; 3 (6)
  • Age and gender-specific disease progression rates to cirrhosis and hepatocellular carcinoma (HCC) in treated and untreated patients with chronic hepatitis B Le, A. K., Toy, M., Yang, H., Trinh, H. N., Zhang, J. Q., Wong, C., Wong, C., Li, J., Nguyen, M. H. WILEY. 2017: 994A
  • Suboptimal rates, trends and predictors of hepatitis B vaccination in a population-based sample of children and adolescents in the United States (US) between 1999 and 2014 Le, M. H., Toy, M., Gane, E. J., So, S., Nguyen, M. H. WILEY. 2017: 1003A
  • Prevalence and predictors of hepatitis B immunization in adults without immunity for hepatitis B from 1999-2014: a population-based study of 27,713 adults in the US Le, M. H., Toy, M., Gane, E. J., So, S., Nguyen, M. H. WILEY. 2017: 1004A
  • Population Health Impact and Cost-Effectiveness of Chronic Hepatitis B Diagnosis, Care, and Treatment in the United States A National Strategy for the Elimination of Hepatitis B and C: Phase Two Report Toy, M. The National Academies of Sciences. 2017: Appendix 1
  • Viral Hepatitis Strategic Information and Modelling Reference Group Meeting report 14–16 June 2016 WHO headquarters, Geneva, Switzerland Hutin, Y., Aggarwal, R., Cowie, B., Hallet, T., Hutchinson, S., Razavi, H., Abu-Raddad, L., Toy, M., Chhatwal, J. World Health Organization. 2016
  • Emerging Technologies for Point-of-Care Management of HIV Infection ANNUAL REVIEW OF MEDICINE, VOL 66 Shafiee, H., Wang, S., Inci, F., Toy, M., Henrich, T. J., Kuritzkes, D. R., Demirci, U. 2015; 66: 387-405


    The global HIV/AIDS pandemic has resulted in 39 million deaths to date, and there are currently more than 35 million people living with HIV worldwide. Prevention, screening, and treatment strategies have led to major progress in addressing this disease globally. Diagnostics is critical for HIV prevention, screening and disease staging, and monitoring antiretroviral therapy (ART). Currently available diagnostic assays, which include polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and western blot (WB), are complex, expensive, and time consuming. These diagnostic technologies are ill suited for use in low- and middle-income countries, where the challenge of the HIV/AIDS pandemic is most severe. Therefore, innovative, inexpensive, disposable, and rapid diagnostic platform technologies are urgently needed. In this review, we discuss challenges associated with HIV management in resource-constrained settings and review the state-of-the-art HIV diagnostic technologies for CD4(+) T lymphocyte count, viral load measurement, and drug resistance testing.

    View details for DOI 10.1146/annurev-med-092112-143017

    View details for Web of Science ID 000348560300026

    View details for PubMedID 25423597

  • Cost-Effectiveness and Cost Thresholds of Generic and Brand Drugs in a National Chronic Hepatitis B Treatment Program in China. PloS one Toy, M., Hutton, D. W., So, S. K. 2015; 10 (11)


    Chronic liver disease and liver cancer associated with chronic hepatitis B (CHB) are leading causes of death among adults in China. Although newborn hepatitis B immunization has successfully reduced the prevalence of CHB in children, about 100 million Chinese adults remain chronically infected. If left unmanaged, 15-25% will die from liver cancer or liver cirrhosis. Antiviral treatment is not necessary for all patients with CHB, but when it is indicated, good response to treatment would prevent disease progression and reduce disease mortality and morbidity, and costly complications. The aim of this study is to analyze the cost-effectiveness of generic and brand antiviral drugs for CHB treatment in China, and assessing various thresholds at which a highly potent, low resistance antiviral drug would be cost-saving and/or cost-effective to introduce in a national treatment program. We developed a Markov simulation model of disease progression using effectiveness and cost data from the medical literature. We measured life-time costs, quality adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), and clinical outcomes. The no treatment strategy incurred the highest health care costs ($12,932-$25,293) per patient, and the worst health outcomes, compared to the antiviral treatment strategies. Monotherapy with either entecavir or tenofovir yielded the most QALYs (14.10-19.02) for both HBeAg-positive and negative patients, with or without cirrhosis. Threshold analysis showed entercavir or tenofovir treatment would be cost saving if the drug price is $32-75 (195-460 RMB) per month, highly cost-effective at $62-110 (379-670 RMB) per month and cost-effective at $63-120 (384-734 RMB) per month. This study can support policy decisions regarding the implementation of a national health program for chronic hepatitis B treatment in China at the population level.

    View details for DOI 10.1371/journal.pone.0139876

    View details for PubMedID 26536626

  • Recent advances in micro/nanotechnologies for global control of hepatitis B infection BIOTECHNOLOGY ADVANCES Yildiz, U. H., Inci, F., Wang, S., Toy, M., Tekin, H. C., Javaid, A., Lau, D. T., Demirci, U. 2015; 33 (1): 178-190


    The control of hepatitis B virus (HBV) infection is a challenging task, specifically in developing countries there is limited access to diagnostics and antiviral treatment mainly due to high costs and insufficient healthcare infrastructure. Although the current diagnostic technologies can reliably detect HBV, they are relatively laborious, impractical and require expensive resources that are not suitable for resource-limited settings. Advances in micro/nanotechnology are pioneering the development of new generation methodologies in diagnosis and screening of HBV. Owing to combination of nanomaterials (metal/inorganic nanoparticles, carbon nanotubes, etc.) with microfabrication technologies, utilization of miniaturized sensors detecting HBV and other viruses from ultra-low volume of blood, serum and plasma is realized. The state-of-the-art microfluidic devices with integrated nanotechnologies potentially allow for inexpensive HBV screening at low cost. This review aims to highlight recent advances in nanotechnology and microfabrication processes that are employed for developing point-of-care (POC) HBV assays.

    View details for DOI 10.1016/j.biotechadv.2014.11.003

    View details for Web of Science ID 000351321400013

    View details for PubMedID 25450190

  • Population Health Impact and Cost-Effectiveness of Monitoring Inactive Chronic Hepatitis B and Treating Eligible Patients in Shanghai, China HEPATOLOGY Toy, M., Salomon, J. A., Jiang, H., Gui, H., Wang, H., Wang, J., Richardus, J. H., Xie, Q. 2014; 60 (1): 46-55


    Inactive chronic hepatitis B (CHB) carriers make up the largest group of hepatitis B virus-infected patients, and China bears the largest total CHB burden of any country. We therefore assessed the population health impact and cost-effectiveness of a strategy of lifelong monitoring for inactive CHB and treatment of eligible patients in Shanghai, China. We used a computer simulation model to project health outcomes among a population cohort of CHB based on age-specific prevalence of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and cirrhosis. Using a Markov model we simulated patients' progression through a discrete series of health states, and compared current practice to a monitor and treat (M&T) strategy. We measured lifetime costs and quality-adjusted life years (QALYs) (both discounted at 3% per year), incremental cost-effectiveness ratios (ICERs), and clinical outcomes such as development of hepatocellular carcinoma (HCC). We estimated that there are 1.5 million CHB-infected persons in Shanghai. The M&T strategy costs US$20,730 per patient and yields a discounted QALY of 15.45, which represents incremental costs and health benefits of US$275 and 0.10 QALYs compared to current practice, and an ICER of US$2,996 per QALY gained. In the base case, we estimated that the M&T strategy will reduce HCC and CHB-related mortality by only around 1%. If variables such as adherence to monitoring and treatment could be substantially improved the M&T strategy could reduce HCC by 70% and CHB-related mortality by 83%.Lifelong monitoring of inactive CHB carriers is cost-effective in Shanghai according to typical benchmarks for value for money, but achieving substantial population-level health gains depends on identifying more CHB-infected cases in the population, and increasing rates of treatment, monitoring, and treatment adherence.

    View details for DOI 10.1002/hep.26934

    View details for Web of Science ID 000337969000010

    View details for PubMedID 24990105

  • Preventing hepatocellular carcinoma: the crucial role of chronic hepatitis B monitoring and antiviral treatment Hepatic Oncology Toy, M., Demirci, U., So, S. 2014; 1 (3): 255-257
  • Cost-effective interventions in the control of chronic hepatitis B infection European Medical Journal: Hepatology Toy, M. 2014; 1: 71-76
  • Cost-effectiveness of viral hepatitis B & C treatment BEST PRACTICE & RESEARCH IN CLINICAL GASTROENTEROLOGY Toy, M. 2013; 27 (6): 973-985


    With the availability of effective antiviral therapies for chronic viral hepatitis B and C, cost-effectiveness studies have been performed to assess the outcomes and costs of these therapies to support health policy. It is now accepted that treatment of active CHB is cost-effective versus no treatment, although there are a variety of options. And with the new developments around CHC treatment and diagnostic tools it is of interest to both the clinician and policy makers to know both the costs and effects of these choices. The purpose of this article is to provide the reader with an insight into the recent treatment developments and cost-effectiveness issues related to chronic hepatitis B and C treatment, and an overview of recent cost-effectiveness studies evolving around HBV and HCV therapy.

    View details for DOI 10.1016/j.bpg.2013.08.020

    View details for Web of Science ID 000327806500013

    View details for PubMedID 24182615

  • A Mathematical Approach for Evaluating Markov Models in Continuous Time without Discrete-Event Simulation MEDICAL DECISION MAKING van Rosmalen, J., Toy, M., O'Mahony, J. F. 2013; 33 (6): 767-779


    Markov models are a simple and powerful tool for analyzing the health and economic effects of health care interventions. These models are usually evaluated in discrete time using cohort analysis. The use of discrete time assumes that changes in health states occur only at the end of a cycle period. Discrete-time Markov models only approximate the process of disease progression, as clinical events typically occur in continuous time. The approximation can yield biased cost-effectiveness estimates for Markov models with long cycle periods and if no half-cycle correction is made. The purpose of this article is to present an overview of methods for evaluating Markov models in continuous time. These methods use mathematical results from stochastic process theory and control theory. The methods are illustrated using an applied example on the cost-effectiveness of antiviral therapy for chronic hepatitis B. The main result is a mathematical solution for the expected time spent in each state in a continuous-time Markov model. It is shown how this solution can account for age-dependent transition rates and discounting of costs and health effects, and how the concept of tunnel states can be used to account for transition rates that depend on the time spent in a state. The applied example shows that the continuous-time model yields more accurate results than the discrete-time model but does not require much computation time and is easily implemented. In conclusion, continuous-time Markov models are a feasible alternative to cohort analysis and can offer several theoretical and practical advantages.

    View details for DOI 10.1177/0272989X13487947

    View details for Web of Science ID 000327813000004

    View details for PubMedID 23715464

  • Cost-effectiveness of Augmenting Universal Hepatitis B Vaccination With Immunoglobin Treatment PEDIATRICS Chen, S. C., Toy, M., Yeh, J. M., Wang, J., Resch, S. 2013; 131 (4): E1135-E1143


    To compare the cost-effectiveness of hepatitis B virus (HBV) control strategies combining universal vaccination with hepatitis B immunoglobulin (HBIG) treatment for neonates of carrier mothers.Drawing on Taiwan's experience, we developed a decision-analytic model to estimate the clinical and economic outcomes for 4 strategies: (1) strategy V-universal vaccination; (2) strategy S-V plus screening for hepatitis B surface antigen (HBsAg) and HBIG treatment for HBsAg-positive mothers' neonates; (3) strategy E-V plus screening for hepatitis B e-antigen (HBeAg), HBIG for HBeAg-positive mothers' neonates; (4) strategy S&E-V plus screening for HBsAg then HBeAg, HBIG for all HBeAg-positive, and some HBeAg-negative/HBsAg-positive mothers' neonates.Strategy S averted the most infections, followed by S&E, E, and V. In most cases, the more effective strategies were also more costly. The willingness-to-pay (WTP) above which strategy S was cost-effective rose as carrier rate declined and was <$4000 per infection averted for carrier rates >5%. The WTP below which strategy V was optimal also increased as carrier rate declined, from $1400 at 30% carrier rate to $3100 at 5% carrier rate. Strategies involving E were optimal for an intermediate range of WTP that narrowed as carrier rate declined.HBIG treatment for neonates of HBsAg carrier mothers is likely to be a cost-effective addition to universal vaccination, particularly in settings with adequate health care infrastructure. Targeting HBIG to neonates of higher risk HBeAg-positive mothers may be preferred where WTP is moderate. However, in very resource-limited settings, universal vaccination alone is optimal.

    View details for DOI 10.1542/peds.2012-1262

    View details for Web of Science ID 000318269500012

    View details for PubMedID 23530168

  • High disease progression and medical costs if not detected in a high endemic chronic hepatitis B region: a cost-effectiveness analysis Journal of Antivirals and Antiretrovirals Li, S., Onder, F. O., Xie, Q., Liu, Y., Toy, M. 2013; 5: 154-159
  • The cost-effectiveness of treating chronic hepatitis B patients in a median endemic and middle income country EUROPEAN JOURNAL OF HEALTH ECONOMICS Toy, M., Onder, F. O., Idilman, R., Kabacam, G., Richardus, J. H., Bozdayi, M., Akdogan, M., Kuloglu, Z., Kansu, A., Schalm, S., Yurdaydin, C. 2012; 13 (5): 663-676


    Chronic hepatitis B (CHB) infection is a serious public health problem due to its potential liver disease sequelae and highly expensive medical costs such as the need for liver transplantation. The aim of this study was to quantify the burden of active CHB in terms of mortality and morbidity, the eligibility of antiviral treatment and to assess various treatment scenarios and possible salvage combinations for cost-effectiveness.A population cohort from a large data base of chronic hepatitis B patients was constructed and stratified according to 10-year age groups, the prevalence of HBsAg, HBV DNA level, ALT level, HBeAg status and the presence of cirrhosis. An age-specific Markov model for disease progression and cost-effectiveness analysis was constructed and calibrated for the specific population setting.Of about 3.2 million estimated HBsAg carriers, 25% are eligible for treatment. If the active cohort remains untreated, 31% will die due to liver related complications. Within a 20-year period, 11% will have developed decompensated cirrhosis, 12% liver cancer and 6% will need liver transplantation. Quality adjusted life years (QALYs) for the no treatment scenario ranged from 9.3 to 14.0. For scenarios with antiviral treatment, QALYs ranged from 9.9 to 14.5 for lamivudine, 13.0-17.5 for salvage therapy, and 16.6-19.0 for the third generation drugs entecavir and tenofovir.In a country with considerable amount of active CHB patients, monotherapy with a highly potent third generation drug has the most health-gain, and is cost-effective in both HBeAg-positive and negative in all stages of liver disease.

    View details for DOI 10.1007/s10198-012-0413-8

    View details for Web of Science ID 000308029500013

    View details for PubMedID 22815098

  • Age- and region-specific hepatitis B prevalence in Turkey estimated using generalized linear mixed models: a systematic review BMC INFECTIOUS DISEASES Toy, M., Onder, F. O., Woermann, T., Bozdayi, A. M., Schalm, S. W., Borsboom, G. J., van Rosmalen, J., Richardus, J. H., Yurdaydin, C. 2011; 11


    To provide a clear picture of the current hepatitis B situation, the authors performed a systematic review to estimate the age- and region-specific prevalence of chronic hepatitis B (CHB) in Turkey.A total of 339 studies with original data on the prevalence of hepatitis B surface antigen (HBsAg) in Turkey and published between 1999 and 2009 were identified through a search of electronic databases, by reviewing citations, and by writing to authors. After a critical assessment, the authors included 129 studies, divided into categories: 'age-specific'; 'region-specific'; and 'specific population group'. To account for the differences among the studies, a generalized linear mixed model was used to estimate the overall prevalence across all age groups and regions. For specific population groups, the authors calculated the weighted mean prevalence.The estimated overall population prevalence was 4.57, 95% confidence interval (CI): 3.58, 5.76, and the estimated total number of CHB cases was about 3.3 million. The outcomes of the age-specific groups varied from 2.84, (95% CI: 2.60, 3.10) for the 0-14-year olds to 6.36 (95% CI: 5.83, 6.90) in the 25-34-year-old group.There are large age-group and regional differences in CHB prevalence in Turkey, where CHB remains a serious health problem.

    View details for DOI 10.1186/1471-2334-11-337

    View details for Web of Science ID 000300063800001

    View details for PubMedID 22151620

  • Screening and Early Treatment of Migrants for Chronic Hepatitis B Virus Infection Is Cost-Effective GASTROENTEROLOGY Veldhuijzen, I. K., Toy, M., Hahne, S. J., de Wit, G. A., Schalm, S. W., de Man, R. A., Richardus, J. H. 2010; 138 (2): 522-530


    Persons with chronic hepatitis B virus (HBV) infection are at risk of developing cirrhosis and hepatocellular carcinoma. Early detection of chronic HBV infection through screening and treatment of eligible patients has the potential to prevent these sequelae. We assessed the cost-effectiveness in The Netherlands of systematically screening migrants from countries that have high and intermediate HBV infection levels.Epidemiologic data of the expected numbers of patients with active chronic HBV infection in the target population and information about the costs of a screening program were used in a Markov model and used to determine costs and quality-adjusted life years (QALY) for patients who were and were not treated.Compared with the status quo, a 1-time screen for HBV infection can reduce mortality of liver-related diseases by 10%. Using base case estimates, the incremental cost-effectiveness ratio (ICER) of screening, compared with not screening, is euros (euro) 8966 per QALY gained. The ICER ranged from euro7936 to euro11,705 based on univariate sensitivity analysis, varying parameter values of HBV prevalence, participation rate, success in referral, and treatment compliance. Using multivariate sensitivity analysis for treatment effectiveness, the ICER ranged from euro7222 to euro15,694; for disease progression, it ranged from euro5568 to euro60,418.Early detection and treatment of people with HBV infection can have a large impact on liver-related health outcomes. Systematic screening for chronic HBV infection among migrants is likely to be cost-effective, even using low estimates for HBV prevalence, participation, referral, and treatment compliance.

    View details for DOI 10.1053/j.gastro.2009.10.039

    View details for Web of Science ID 000274300900020

    View details for PubMedID 19879275

  • Potential Impact of Long-Term Nucleoside Therapy on the Mortality and Morbidity of Active Chronic Hepatitis B HEPATOLOGY Toy, M., Veldhuijzen, I. K., de Man, R. A., Richardus, J. H., Schalm, S. W. 2009; 50 (3): 743-751


    The potential impact of long-term antiviral therapy on the burden of chronic hepatitis B has hardly been documented. The aim of this study was to estimate the effects of prolonged antiviral therapy and antiviral resistance on the mortality and morbidity of active chronic hepatitis B patients. A population cohort of chronic hepatitis B patients in the Netherlands was constructed and stratified according to 10-year age groups, prevalence of hepatitis B surface antigen, hepatitis B virus DNA level, alanine aminotransferase level, hepatitis B e antigen status, and presence of cirrhosis. A Markov model was created to mathematically simulate the cohort's progression through a finite series of health states. The analysis was performed on the basis of four scenarios: natural history, long-term therapy with a high-resistance profile drug without or with salvage, and therapy with a low-resistance profile drug. It has been estimated that there were 64,000 people (0.4%) suffering from chronic hepatitis B infection in the Netherlands in 2005, with 6521 (10%) of them having high viremia and elevated alanine aminotransferase levels. Within a 20-year period, 1725 (26%) of the 6521 patients in the active chronic hepatitis B cohort will die because of liver-related causes. Of the 5685 without cirrhosis at entry, 1671 (29%) will develop cirrhosis. Of those 836 with cirrhosis at entry, 619 (74%) will die within a 20-year period. If this active chronic hepatitis B cohort is fully detected and treated, mortality related to liver disease can be reduced by 80% if a low-resistance profile drug is chosen from the start. The effect is due to both the reduction in complications of cirrhosis and the prevention of the development of cirrhosis.Long-term antiviral therapy with a strategy that minimizes or controls resistance will have a major preventive effect on liver-related mortality and morbidity.

    View details for DOI 10.1002/hep.23061

    View details for Web of Science ID 000269551100013

    View details for PubMedID 19585616

  • Transmission routes of hepatitis B virus infection in chronic hepatitis B patients in the Netherlands JOURNAL OF MEDICAL VIROLOGY Toy, M., Veldhuijzen, I. K., Mostert, M. C., de Man, R. A., Richardus, J. H. 2008; 80 (3): 399-404


    The Netherlands is a low endemic country for hepatitis B virus (HBV). Rotterdam, a city in The Netherlands harbors a large group of chronic hepatitis B (CHB) patients of which most are born abroad. The study included 464 consecutive CHB patients who were reported to the Municipal Public Health Service in Rotterdam from January 1, 2002 to September 15, 2005. The HBV genotypes, possible transmission routes of infection and travel history of CHB patients born in The Netherlands, were compared with those CHB patients living in The Netherlands but who were foreign-born, taking into account the ethnicity of the mother. Of the 464 patients with CHB infection, 14% were Dutch-born and 86% were foreign-born. The CHB patients in the Dutch-born group had genotypes A (35%), B (15%), C (11%), D (37%), and G (2%). In the foreign-born group, the distribution of genotypes was A (20%), B (15%), C (11%), D (40%), and E (15%). In the Dutch-born group, sexual transmission accounted for a larger proportion of infections (P < 0.0001) compared to the foreign-born group, whereas perinatal transmission is reported to be higher in the foreign-born group and in the Dutch-born group with a foreign mother. The genotypes of the chronic HBV strains determined corresponded well with the HBV genotypes expected from the countries of origin of the patients or their mothers. Genotypes A and D are predominant in CHB patients in The Netherlands.

    View details for DOI 10.1002/jmv.21098

    View details for Web of Science ID 000252756500004

    View details for PubMedID 18205235