skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Screening for hepatitis D and PEG-Interferon over Tenofovir enhance general hepatitis control efforts in Brazil

Abstract

Hepatitis D virus (HDV), which requires the presence of hepatitis B virus (HBV), is a deadly yet neglected disease that rapidly leads to liver cancer and disease-induced mortality. This co-dependence creates complex transmission dynamics that make it difficult to predict the efficacy of interventions aimed at HBV and/or HDV control in endemic regions, such as certain municipalities of Brazil, where up to 65% of HBV-infected persons are co-infected. We created a mathematical model that captures the joint transmission dynamics of HBV and HDV, incorporating mother-to-child, sexual and household transmission. With an aim to minimize the number of total infections and disease-induced mortality in 2027, we then determined optimal strategies for Brazil and its sub-regions under a constrained budget, which was dynamically allocated among HBV and HDV screening, HBV and HDV treatment, HBV newborn and adult vaccination, and awareness programs. Three treatment options were considered, namely: Tenofovir, PEGylated-Interferon, and nucleic acid polymers (NAP). The additional cost of HDV screening and the use of a more expensive PEGylated-Interferon are offset by not wasting resources on treating co-infected persons with Tenofovir. The introductory price of NAP treatment must be less than $16,000 per course to become competitive with Tenofovir and PEGylated-Interferon in Brazil.more » Additional screening for HDV is beneficial, even in a low HBV and HDV endemic regions of Brazil. We recommend PEGylated-Interferon, wherever possible, for both HBV and HDV. If PEGylated-Interferon is not available in abundance, PEGylated-Interferon for co-infections and 4-year Tenofovir treatment for mono-infections is recommended.« less

Authors:
ORCiD logo [1];  [1]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE; National Inst. of Health (NIH) (United States)
OSTI Identifier:
1471303
Report Number(s):
LA-UR-18-28686
Journal ID: ISSN 1932-6203
Grant/Contract Number:  
AC52-06NA25396; R01-AI116868; R01-AI028433; R01-OD011095; R01-AI087520
Resource Type:
Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 13; Journal Issue: 9; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Biological Science

Citation Formats

Goyal, Ashish, and Romero-Severson, Ethan Obie. Screening for hepatitis D and PEG-Interferon over Tenofovir enhance general hepatitis control efforts in Brazil. United States: N. p., 2018. Web. doi:10.1371/journal.pone.0203831.
Goyal, Ashish, & Romero-Severson, Ethan Obie. Screening for hepatitis D and PEG-Interferon over Tenofovir enhance general hepatitis control efforts in Brazil. United States. doi:https://doi.org/10.1371/journal.pone.0203831
Goyal, Ashish, and Romero-Severson, Ethan Obie. Fri . "Screening for hepatitis D and PEG-Interferon over Tenofovir enhance general hepatitis control efforts in Brazil". United States. doi:https://doi.org/10.1371/journal.pone.0203831. https://www.osti.gov/servlets/purl/1471303.
@article{osti_1471303,
title = {Screening for hepatitis D and PEG-Interferon over Tenofovir enhance general hepatitis control efforts in Brazil},
author = {Goyal, Ashish and Romero-Severson, Ethan Obie},
abstractNote = {Hepatitis D virus (HDV), which requires the presence of hepatitis B virus (HBV), is a deadly yet neglected disease that rapidly leads to liver cancer and disease-induced mortality. This co-dependence creates complex transmission dynamics that make it difficult to predict the efficacy of interventions aimed at HBV and/or HDV control in endemic regions, such as certain municipalities of Brazil, where up to 65% of HBV-infected persons are co-infected. We created a mathematical model that captures the joint transmission dynamics of HBV and HDV, incorporating mother-to-child, sexual and household transmission. With an aim to minimize the number of total infections and disease-induced mortality in 2027, we then determined optimal strategies for Brazil and its sub-regions under a constrained budget, which was dynamically allocated among HBV and HDV screening, HBV and HDV treatment, HBV newborn and adult vaccination, and awareness programs. Three treatment options were considered, namely: Tenofovir, PEGylated-Interferon, and nucleic acid polymers (NAP). The additional cost of HDV screening and the use of a more expensive PEGylated-Interferon are offset by not wasting resources on treating co-infected persons with Tenofovir. The introductory price of NAP treatment must be less than $16,000 per course to become competitive with Tenofovir and PEGylated-Interferon in Brazil. Additional screening for HDV is beneficial, even in a low HBV and HDV endemic regions of Brazil. We recommend PEGylated-Interferon, wherever possible, for both HBV and HDV. If PEGylated-Interferon is not available in abundance, PEGylated-Interferon for co-infections and 4-year Tenofovir treatment for mono-infections is recommended.},
doi = {10.1371/journal.pone.0203831},
journal = {PLoS ONE},
number = 9,
volume = 13,
place = {United States},
year = {2018},
month = {9}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Save / Share:

Works referenced in this record:

Hepatitis delta infection – Current and new treatment options
journal, June 2017

  • Elazar, Menashe; Koh, Christopher; Glenn, Jeffrey S.
  • Best Practice & Research Clinical Gastroenterology, Vol. 31, Issue 3
  • DOI: 10.1016/j.bpg.2017.05.001

Modeling the transmission dynamics and control of hepatitis B virus in China
journal, January 2010


A mathematical model of hepatitis B virus transmission and its application for vaccination strategy in China
journal, August 2000

  • Zhao, Shoujun; Xu, Zhiyi; Lu, Ying
  • International Journal of Epidemiology, Vol. 29, Issue 4
  • DOI: 10.1093/ije/29.4.744

The Cost-effectiveness of Screening for Chronic Hepatitis B Infection in the United States
journal, June 2011

  • Eckman, Mark H.; Kaiser, Tiffany E.; Sherman, Kenneth E.
  • Clinical Infectious Diseases, Vol. 52, Issue 11
  • DOI: 10.1093/cid/cir199

Chronic HDV/HBV co-infection: Predictors of disease stage – a case series of HDV-3 patients
journal, December 2014

  • Braga, Wornei Silva Miranda; de Oliveira, Cintia Mara Costa; de Araújo, José Ribamar
  • Journal of Hepatology, Vol. 61, Issue 6
  • DOI: 10.1016/j.jhep.2014.05.041

The transmission dynamics of hepatitis B in the UK: a mathematical model for evaluating costs and effectiveness of immunization programmes
journal, February 1996


Epidemiology and Molecular Characterization of Hepatitis B Virus Infection in Isolated Villages in the Western Brazilian Amazon
journal, October 2012

  • Castilho, Márcia da Costa; Costa de Oliveira, Cintia Mara; Gimaque, João Bosco de Lima
  • The American Journal of Tropical Medicine and Hygiene, Vol. 87, Issue 4
  • DOI: 10.4269/ajtmh.2012.12-0083

A hepatitis B-free generation in China: from dream to reality
journal, October 2016


Is Hepatitis Delta infections important in Brazil?
journal, September 2016

  • Cicero, Maira Ferreira; Pena, Nathalia Mantovani; Santana, Luiz Claudio
  • BMC Infectious Diseases, Vol. 16, Issue 1
  • DOI: 10.1186/s12879-016-1856-9

Treatment of children with HBeAg-positive chronic hepatitis B: A systematic review and meta-analysis
journal, December 2014


Distribution of hepatitis B infection in Brazil: the epidemiological situation at the beginning of the 21 st century
journal, December 2015


AASLD guidelines for treatment of chronic hepatitis B: Hepatology, Month 2015
journal, November 2015

  • Terrault, Norah A.; Bzowej, Natalie H.; Chang, Kyong-Mi
  • Hepatology, Vol. 63, Issue 1
  • DOI: 10.1002/hep.28156

Hepatitis B cure: From discovery to regulatory approval: Lok et al.
journal, August 2017

  • Lok, Anna S.; Zoulim, Fabien; Dusheiko, Geoffrey
  • Hepatology, Vol. 66, Issue 4
  • DOI: 10.1002/hep.29323

Hepatitis B: Epidemiology and prevention in developing countries
journal, January 2012


Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis delta
journal, June 2014

  • Heidrich, Benjamin; Yurdaydın, Cihan; Kabaçam, Gökhan
  • Hepatology, Vol. 60, Issue 1
  • DOI: 10.1002/hep.27102

A mathematical model to estimate global hepatitis B disease burden and vaccination impact
journal, October 2005

  • Goldstein, Susan T.; Zhou, Fangjun; Hadler, Stephen C.
  • International Journal of Epidemiology, Vol. 34, Issue 6
  • DOI: 10.1093/ije/dyi206

Clinical and virological heterogeneity of hepatitis delta in different regions world-wide: The Hepatitis Delta International Network (HDIN)
journal, October 2017

  • Wranke, Anika; Pinheiro Borzacov, Lourdes M.; Parana, Raymundo
  • Liver International, Vol. 38, Issue 5
  • DOI: 10.1111/liv.13604

Progress in vaccination towards hepatitis B control and elimination in the Region of the Americas
journal, April 2017

  • Ropero Álvarez, Alba Maria; Pérez-Vilar, Silvia; Pacis-Tirso, Carmelita
  • BMC Public Health, Vol. 17, Issue 1
  • DOI: 10.1186/s12889-017-4227-6

Incidence of hepatitis C in Brazil
journal, December 2015

  • Hanus, Juliét Silveira; Ceretta, Luciane Bisognin; Simões, Priscyla Waleska
  • Revista da Sociedade Brasileira de Medicina Tropical, Vol. 48, Issue 6
  • DOI: 10.1590/0037-8682-0230-2015

Finding optimal vaccination strategies for pandemic influenza using genetic algorithms
journal, May 2005

  • Patel, Rajan; Longini, Ira M.; Elizabeth Halloran, M.
  • Journal of Theoretical Biology, Vol. 234, Issue 2
  • DOI: 10.1016/j.jtbi.2004.11.032

Molecular epidemiology of hepatitis B and hepatitis delta viruses circulating in the Western Amazon region, North Brazil
journal, February 2014

  • Crispim, Myuki Alfaia Esashika; Fraiji, Nelson Abrahim; Campello, Sonia Cordeiro
  • BMC Infectious Diseases, Vol. 14, Issue 1
  • DOI: 10.1186/1471-2334-14-94

Hepatotropic viruses in the Brazilian Amazon: a health threat
journal, January 2008

  • Paraná, Raymundo; Vitvitski, Ludmila; Pereira, Joao Eduardo
  • Brazilian Journal of Infectious Diseases, Vol. 12, Issue 3
  • DOI: 10.1590/s1413-86702008000300017

Economic evaluation of treatments for chronic hepatitis B
journal, July 2013

  • Wiens, Astrid; Lenzi, Luana; Venson, Rafael
  • The Brazilian Journal of Infectious Diseases, Vol. 17, Issue 4
  • DOI: 10.1016/j.bjid.2012.12.005

Roadmap to control HBV and HDV epidemics in China
journal, June 2017


Brazilian hepatitis B vaccine: a six-year follow-up in adolescents
journal, December 2012

  • Alexandre, Kamilla Vêncio Frauzino; Martins, Regina Maria Bringel; Souza, Márcia Maria de
  • Memórias do Instituto Oswaldo Cruz, Vol. 107, Issue 8
  • DOI: 10.1590/s0074-02762012000800016

How Hepatitis D Virus Can Hinder the Control of Hepatitis B Virus
journal, April 2009


An Estimate of the Cost of Hepatitis C Treatment for the Brazilian Health System
journal, December 2012

  • Blatt, Carine Raquel; Bernardo, Noemia Liege Maria da Cunha; Rosa, Junior Andre
  • Value in Health Regional Issues, Vol. 1, Issue 2
  • DOI: 10.1016/j.vhri.2012.10.001

Review article: current antiviral therapy of chronic hepatitis B: Review: therapy of chronic hepatitis B
journal, October 2011


Recognizing the impact of endemic hepatitis D virus on hepatitis B virus eradication
journal, December 2016


Household survey of hepatitis B vaccine coverage among Brazilian children
journal, August 2009


High Prevalence of Hepatitis b Virus and Hepatitis d Virus in the Western Brazilian Amazon
journal, October 2005

  • Compri, Adriana Parise; Macedo, Vanise; Moreira, Regina CÉLia
  • The American Journal of Tropical Medicine and Hygiene, Vol. 73, Issue 4
  • DOI: 10.4269/ajtmh.2005.73.808

Implementation and Impact of HAV and HBV Vaccination Programs in South America
journal, September 2013


Changes in sexual behavior following a sex education program in Brazilian public schools
journal, May 2009

  • Andrade, Heloísa Helena Siqueira Monteiro; Mello, Maeve Brito de; Sousa, Maria Helena
  • Cadernos de Saúde Pública, Vol. 25, Issue 5
  • DOI: 10.1590/s0102-311x2009000500023

Hepatitis D Virus: Introduction and Epidemiology
journal, July 2015


Hepatitis Delta Virus: Replication Strategy and Upcoming Therapeutic Options for a Neglected Human Pathogen
journal, July 2017


HBV life cycle and novel drug targets
journal, March 2011


Treatment of children with chronic hepatitis B virus infection in the United States: Patient selection and therapeutic options
journal, October 2010

  • Jonas, Maureen M.; Block, Joan M.; Haber, Barbara A.
  • Hepatology, Vol. 52, Issue 6
  • DOI: 10.1002/hep.23934

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection
journal, August 2017


Hepatitis D in Children
journal, January 2015

  • Xue, Megan M.; Glenn, Jeffrey S.; Leung, Daniel H.
  • Journal of Pediatric Gastroenterology and Nutrition, Vol. 61, Issue 3
  • DOI: 10.1097/mpg.0000000000000859

Future Therapy for Hepatitis B Virus: Role of Immunomodulators
journal, November 2016

  • Pham, Edward A.; Perumpail, Ryan B.; Fram, Benjamin J.
  • Current Hepatology Reports, Vol. 15, Issue 4
  • DOI: 10.1007/s11901-016-0315-9

Hepatitis B Virus Epidemiology
journal, May 2015


Low prevalence of hepatitis B virus, hepatitis D virus and hepatitis C virus among patients with human immunodeficiency virus or acquired immunodeficiency syndrome in the Brazilian Amazon basin
journal, December 2006

  • Braga, Wornei Silva Miranda; Castilho, Márcia da Costa; Santos, Isabelle Cristina Vale dos
  • Revista da Sociedade Brasileira de Medicina Tropical, Vol. 39, Issue 6
  • DOI: 10.1590/s0037-86822006000600001

Dynamics of in vivo hepatitis D virus infection
journal, June 2016


Cost-Effectiveness Analysis of a Universal Infant Immunization Program with Meningococcal C Conjugate Vaccine in Brazil
journal, December 2011

  • de Soarez, Patricia Coelho; Sartori, Ana Marli C.; de Andrade Lagoa Nóbrega, Laura
  • Value in Health, Vol. 14, Issue 8
  • DOI: 10.1016/j.jval.2011.05.045

The Impact of Vaccination and Antiviral Therapy on Hepatitis B and Hepatitis D Epidemiology
journal, October 2014


Hepatitis D virus infection in the Western Brazilian Amazon - far from a vanishing disease
journal, December 2012

  • Braga, Wornei Silva Miranda; Castilho, Márcia da Costa; Borges, Fabiane Giovanella
  • Revista da Sociedade Brasileira de Medicina Tropical, Vol. 45, Issue 6
  • DOI: 10.1590/s0037-86822012000600007

Low Prevalence of Hepatitis B and C Virus Markers among Children and Adolescents
journal, January 2014

  • Villar, Livia Melo; Amado, Luciane Almeida; de Almeida, Adilson José
  • BioMed Research International, Vol. 2014
  • DOI: 10.1155/2014/324638

Hepatotropic viruses in the Brazilian Amazon: a health threat
journal, January 2008

  • Paraná, Raymundo; Vitvitski, Ludmila; Pereira, Joao Eduardo
  • Brazilian Journal of Infectious Diseases, Vol. 12, Issue 3
  • DOI: 10.1590/S1413-86702008000300017

The transmission dynamics of hepatitis B in the UK: a mathematical model for evaluating costs and effectiveness of immunization programmes
journal, February 1996


Brazilian hepatitis B vaccine: a six-year follow-up in adolescents
journal, December 2012

  • Alexandre, Kamilla Vêncio Frauzino; Martins, Regina Maria Bringel; Souza, Márcia Maria de
  • Memórias do Instituto Oswaldo Cruz, Vol. 107, Issue 8
  • DOI: 10.1590/S0074-02762012000800016

Low prevalence of hepatitis B virus, hepatitis D virus and hepatitis C virus among patients with human immunodeficiency virus or acquired immunodeficiency syndrome in the Brazilian Amazon basin
journal, December 2006

  • Braga, Wornei Silva Miranda; Castilho, Márcia da Costa; Santos, Isabelle Cristina Vale dos
  • Revista da Sociedade Brasileira de Medicina Tropical, Vol. 39, Issue 6
  • DOI: 10.1590/S0037-86822006000600001

Hepatitis D virus infection in the Western Brazilian Amazon - far from a vanishing disease
journal, December 2012

  • Braga, Wornei Silva Miranda; Castilho, Márcia da Costa; Borges, Fabiane Giovanella
  • Revista da Sociedade Brasileira de Medicina Tropical, Vol. 45, Issue 6
  • DOI: 10.1590/S0037-86822012000600007

Changes in sexual behavior following a sex education program in Brazilian public schools
journal, May 2009

  • Andrade, Heloísa Helena Siqueira Monteiro; Mello, Maeve Brito de; Sousa, Maria Helena
  • Cadernos de Saúde Pública, Vol. 25, Issue 5
  • DOI: 10.1590/S0102-311X2009000500023

A hepatitis B-free generation in China: from dream to reality
journal, October 2016


Hepatitis D in Children
journal, January 2015

  • Xue, Megan M.; Glenn, Jeffrey S.; Leung, Daniel H.
  • Journal of Pediatric Gastroenterology and Nutrition, Vol. 61, Issue 3
  • DOI: 10.1097/MPG.0000000000000859