Winston E. Abara, MD, PhD; Amir Qaseem, MD, PhD, MHA; Sarah Schillie, MD, MPH, MBA; Brian J. McMahon, MD; Aaron M. Harris, MD, MPH *; for the High Value Care Task Force of the American College of Physicians and the Centers for Disease Control and Prevention
Disclaimer: The conclusions, findings, and opinions expressed by the authors do not necessarily reflect the official position of the Centers for Disease Control and Prevention.
Financial Support: Financial support for the development of this paper comes exclusively from the ACP operating budget.
Disclosures: Dr. McMahon reports that the program he works in, the Alaska Native Tribal Health Consortium Liver Disease and Hepatitis Program (a nonprofit managed care system serving American Indians and Alaska Natives), has 2 research grants from Gilead Sciences for hepatitis C treatment. Dr. McMahon is not an investigator listed on these grants but does see patients who receive free hepatitis C medications supplied by Gilead Sciences in the course of his patient care duties. Dr. Lohr reports that he is the Treasurer of the American College of Physicians. Dr. McLean reports personal fees from Takeda Pharmaceuticals outside the submitted work and is a member of the American College of Physicians Clinical Guidelines Committee and the American College of Rheumatology Quality of Care Committee. Authors not named here have disclosed no conflicts of interest. Authors followed the policy regarding conflicts of interest described at www.annals.org/article.aspx?articleid=745942. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-1106. All financial and intellectual disclosures of interest were declared and potential conflicts were discussed and managed. No individuals were recused from discussion or voting due to conflicts of interest. A record of disclosures of interest is kept for each High Value Care Task Force meeting and conference call and can be viewed at www.acponline.org/clinical-information/high-value-care.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Requests for Single Reprints: Amir Qaseem, MD, PhD, MHA, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106; e-mail, email@example.com.
Current Author Addresses: Drs. Abara, Schillie, and Harris: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road, MS G-37, Atlanta, GA 30333.
Dr. Qaseem: American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106.
Dr. McMahon: Arctic Investigations Program, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 4055 Tudor Center Drive, Anchorage, AK 99508.
Author Contributions: Conception and design: W.E. Abara, A. Qaseem, B.J. McMahon, A.M. Harris, D.M. DeLong, A.M. López, R.M. McLean.
Analysis and interpretation of the data: W.E. Abara, A. Qaseem, B.J. McMahon, A.M. Harris, R. Centor, J.A. Jokela, A.M. López, R.M. McLean.
Drafting of the article: W.E. Abara, A. Qaseem, B.J. McMahon, A.M. Harris.
Critical revision of the article for important intellectual content: W.E. Abara, S. Schillie, B.J. McMahon, A.M. Harris, G.M. Abraham, R. Centor, D.M. DeLong, L.L. Humphrey, J.A. Jokela, R.H. Lohr, A.M. López, R.M. McLean.
Final approval of the article: W.E. Abara, A. Qaseem, S. Schillie, B.J. McMahon, A.M. Harris, G.M. Abraham, R. Centor, D.M. DeLong, H.E. Gantzer, C.A. Horwitch, L.L. Humphrey, J.A. Jokela, J.M.W. Li, R.H. Lohr, A.M. López, R.M. McLean.
Statistical expertise: A. Qaseem.
Obtaining of funding: A. Qaseem.
Administrative, technical, or logistic support: W.E. Abara, A. Qaseem, A.M. Harris.
Collection and assembly of data: W.E. Abara, A.M. Harris.
Vaccination, screening, and linkage to care can reduce the burden of chronic hepatitis B virus (HBV) infection. However, recommendations vary among organizations, and their implementation has been suboptimal. The American College of Physicians' High Value Care Task Force and the Centers for Disease Control and Prevention developed this article to present best practice statements for hepatitis B vaccination, screening, and linkage to care.
A narrative literature review of clinical guidelines, systematic reviews, randomized trials, and intervention studies on hepatitis B vaccination, screening, and linkage to care published between January 2005 and June 2017 was conducted.
Clinicians should vaccinate against hepatitis B virus (HBV) in all unvaccinated adults (including pregnant women) at risk for infection due to sexual, percutaneous, or mucosal exposure; health care and public safety workers at risk for blood exposure; adults with chronic liver disease, end-stage renal disease (including hemodialysis patients), or HIV infection; travelers to HBV-endemic regions; and adults seeking protection from HBV infection.
Clinicians should screen (hepatitis B surface antigen, antibody to hepatitis B core antigen, and antibody to hepatitis B surface antigen) for HBV in high-risk persons, including persons born in countries with 2% or higher HBV prevalence, men who have sex with men, persons who inject drugs, HIV-positive persons, household and sexual contacts of HBV-infected persons, persons requiring immunosuppressive therapy, persons with end-stage renal disease (including hemodialysis patients), blood and tissue donors, persons infected with hepatitis C virus, persons with elevated alanine aminotransferase levels (≥19 IU/L for women and ≥30 IU/L for men), incarcerated persons, pregnant women, and infants born to HBV-infected mothers.
Clinicians should provide or refer all patients identified with HBV (HBsAg-positive) for posttest counseling and hepatitis B–directed care.
Summary of the American College of Physicians and Centers for Disease Control and Prevention best practice advice on hepatitis B vaccination, screening, and linkage to care for adults with chronic HBV infection.
anti-HBc = antibody to hepatitis B core antigen; anti-HBs = antibody to hepatitis B surface antigen; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus.
Table 1. Risk Factors, Prevalence, and Testing Guidelines for Chronic HBV Infection
Table 2. Regions and Countries With HBV Prevalence of 2% or Higher
Table 3. Antibody and Antigen Biomarkers for HBV Infection
Table 4. Barriers to Evidence-Based Practice of Vaccination, Screening, and Linkage to Care for Chronic HBV Infection and Approaches to Overcome Them
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David M Lowe
UCL Immunity and Transplantation
November 27, 2017
Conflict of Interest:
Received support to attend conference and participated in advisory board for Biotest (UK) Ltd. Received travel and accommodation expenses for consultancy work from CSL Behring.
Immunoglobulin therapy is an important consideration in the interpretation of Hepatitis B virus serology
To the Editor,
Jonathan D Alpern, Thomas M Leventhal, Nathan C Bahr
Health Partners Inst., University of Minnesota, University of Kansas
December 14, 2017
High prescription drug costs hinder adequate treatment of hepatitis B in the United States
We read with great interest the excellent Clinical Guideline published by Abara, et al in Annals of Internal Medicine in which the authors highlighted the sub-optimal rates of hepatitis B virus (HBV) screening and treatment in the United States.1 The authors note that many barriers prevent patients with HBV infection from receiving treatment but state that “linkage to care ensures that patients with chronic HBV infection receive treatment when they become eligible…” Although linkage to care is a crucial component of HBV treatment, our experience has been that linkage to care is not sufficient to ensure treatment. High prescription drug costs are a significant system-level barrier that must be considered when caring for patients with HBV infection in the United States.
The National Average Drug Acquisition Cost (NADAC) for a 30-day prescription of the three first-line drugs recommended for the treatment of chronic HBV is as follows: entecavir 0.5 mg tablet (Baraclude) ($115), tenofovir disoproxil fumarate (TDF) 300 mg tablet (Viread) ($1,028), and tenofovir alafenamide (TAF) 25 mg tablet (Vemlidy) ($965). In the case of TDF and TAF, prices likely reflect limited generic competition, a problem not unique to the HBV drug market.2
Since a typical treatment course generally exceeds 1 year (often lifelong), the cost of TAF or TDF can be cost-prohibitive. Although the price of TDF is likely to drop with additional generic entry,3 (as occurred with entecavir) the presence of at least 6 generic manufacturers is often required before the price drops to 25% of the original branded price.4 Until then, our experience has been that regardless of insurance status, HBV treatment is often unaffordable for patients without access to discount programs. Unfortunately, Patient Assistance Programs (PAPs) are not easily navigated, particularly for non-native English speakers, who make up a significant portion of those infected with hepatitis B in the United States. Thus, successful navigation of PAPs frequently requires dedicated support staff to help patients obtain patient assistance.5
In summary, while we agree that linkage to care is a crucial component of hepatitis B care, cost of treatment must be considered as a key systems barrier for patients with HBV in the United States. Navigating this barrier successfully requires a well-funded clinic and dedicated staff willing and able to work closely with patients to ensure that treatment is not unnecessarily delayed, and can be continued without lapses in therapy.
1. Abara WE, Qaseem A, Schillie S, McMahon BJ, Harris AM. Hepatitis B Vaccination, Screening, and Linkage to Care: Best Practice Advice From the American College of Physicians and the Centers for Disease Control and Prevention. Ann Intern Med 2017;167:794-804.
2. Alpern JD, Zhang L, Stauffer WM, Kesselheim AS. Trends in Pricing and Generic Competition Within the Oral Antibiotic Drug Market in the United States. Clin Infect Dis 2017;65:1848-52.
3. ANDA Approval (Food and Drug Administration). 2017. (Accessed December 10, 2017, at https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/090894Orig1s000ltr.pdf.)
4. Generic Competition and Drug Prices. 2015. (Accessed January 20, 2017, at https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm129385.htm.)
5. Duke KS, Raube K, Lipton HL. Patient-assistance programs: assessment of and use by safety-net clinics. Am J Health Syst Pharm 2005;62:726-31.
June 7, 2019
Yeast proteins in HBV (and HPV) vaccines are a fundamental safety flaw
Abara et al. write: “The vaccine is contraindicated in persons with yeast allergies because yeast is a component of the vaccine”.How does a person develop yeast allergy in the first place? IgE mediated yeast allergy develops following administration of a yeast containing vaccine. The Institute of Medicine (now the National Academy of Medicine), reviewed the entire literature from 1950 to 2011 and concluded that antigens in vaccines do induce IgE mediated sensitization (development of allergy) (1).Yeast is everywhere. We eat, breathe and contact yeast all the time. We have therefore co-evolved a finely balanced immunological response, over millions of years of evolution to tolerate or fight yeast (upon infection). Vaccine induced sensitization directed against yeast proteins, disrupts this fine balance and programs the immune system to attack yeast. Thus resulting in numerous diseases. Such diseases include atopic dermatitis (2) dysbiosis and infertility. The specific yeast used in HBV (and HPV) vaccines is saccharomyces cerevisiae. Yeast proteins have molecular mimicry to human self proteins. Vaccine induced anti-saccharomyces cerevisiae antibodies (ASCA) are therefore involved in numerous autoimmune disorders such as systemic lupus erythematosus (SLE), hypothyroidism, vitiligo, narcolepsy, rheumatoid arthritis, etc. (3). Further, yeast proteins are prionogenic. What are the effects of disrupting natural barriers by injecting prionogenic proteins directly into humans (2)? The FDA’s vaccine package inserts assure us that bovine derived material used in vaccines is sourced from BSE-free sources. In other words, free of bovine spongiform encephalopathy (BSE) related prions. But the package inserts have no such assurance about prionogenic yeast proteins in vaccines.Similarly, yeast containing insulin administered to patients with type 1 diabetes results in synthesis of ASCA (4).And of course yeast is just a specific case of the general problem of off-target immune responses against all non-target antigens in vaccines. Vaccines contain numerous non-target antigens that include food, animal, fungal, non-target viral/bacterial proteins, aeroallergens etc. The result is induction of numerous diseases such as life-threatening food allergies, asthma, autism (5) and numerous autoimmune disorders including type 1 diabetes (2).Any discussion of vaccine safety is incomplete if it fails to account for the numerous iatrogenic diseases above.References 1. Stratton K. Adverse Effects of Vaccines: Evidence and Causality [Internet]. Stratton K, Ford A, Rusch E, Clayton EW, editors. Washington, DC: The National Academies Press; 2012. Available from: https://www.nap.edu/catalog/13164/adverse-effects-of-vaccines-evidence-and-causality2. Arumugham V. Vaccines and Biologics injury table based on mechanistic evidence – Mar 2019 [Internet]. 2019. Available from: https://doi.org/10.5281/zenodo.25826343. Arumugham V. Bioinformatics and epidemiological evidence link yeast protein containing HPV and Hepatitis B vaccines to numerous autoimmune disorders such as vitiligo, narcolepsy, hypothyroidism, systemic lupus erythematosus and rheumatoid arthritis [Internet]. 2018. Available from: https://doi.org/10.5281/zenodo.14354034. Sakly W, Mankaï A, Sakly N, Thabet Y, Achour A, Ghedira-Besbes L, et al. Anti-Saccharomyces cerevisiae Antibodies are Frequent in Type 1 Diabetes. Endocr Pathol [Internet]. 2010 Jun 13 [cited 2019 May 28];21(2):108–14. Available from: http://www.ncbi.nlm.nih.gov/pubmed/203870115. Arumugham V, Trushin M V. Role of NMDA receptor autoimmunity induced by food protein containing vaccines, in the etiology of autism, type 1 diabetes, neuropsychiatric and neurodegenerative disorders. Int J Pharm Res [Internet]. 2019 Mar 1 [cited 2019 Apr 15];11(1):428–37. Available from: https://doi.org/10.5281/zenodo.1463600
Abara WE, Qaseem A, Schillie S, et al, for the High Value Care Task Force of the American College of Physicians and the Centers for Disease Control and Prevention. Hepatitis B Vaccination, Screening, and Linkage to Care: Best Practice Advice From the American College of Physicians and the Centers for Disease Control and Prevention. Ann Intern Med. 2017;167:794–804. [Epub ahead of print 21 November 2017]. doi: https://doi.org/10.7326/M17-1106
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Published: Ann Intern Med. 2017;167(11):794-804.
Published at www.annals.org on 21 November 2017
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