In June 2016 the World Health Assembly set the goal of eliminating viral hepatitis as a major public health problem by 2030 (WHO, 2016a). In the first strategy document of its kind, the organization concluded, “hepatitis has been largely ignored as a health and development priority until recently,” despite causing more deaths than HIV, tuberculosis, or malaria (Stanaway et al., 2016; WHO, 2016a; Wiktor and Hutin, 2016).
The world cannot afford to ignore viral hepatitis any longer. The Global Burden of Disease Study estimated 1.45 million deaths from viral hepatitis in 2013 (95 percent confidence interval [CI]: 1.38 to 1.54 million) (Stanaway et al., 2016). Together hepatitis B virus (HBV) and hepatitis C virus (HCV) account for 96 percent of these deaths (Stanaway et al., 2016), more than 21,000 of them in the United States (CDC, 2016). Such loss of life comes at a cost to society, both in the direct financial burden of treatment and indirectly through the loss of adults in their prime—most viral hepatitis deaths cull from the 45 to 64 age group (Ly et al., 2012).
There is no longer any reason to disregard these diseases. There is an effective vaccine to prevent hepatitis B, advances in treatment can prevent most deaths in those chronically infected with HBV, and hepatitis C is now curable with a short course of easily tolerated treatment (Afdhal et al., 2014; Feld et al., 2014). (Box 1-1 describes a national treatment program in Egypt.) Preventive measures against both infections abound (Thomas, 2013). Hepatitis B vaccine confers long-standing immunity in 95 percent of recipients (WHO, 2015); immunization of newborns prevents community acquisition in childhood (Mast et al., 2005). Mother-to-child transmission of HBV, once inevitable, can now be prevented in 85 to 95 percent of cases
(Nelson et al., 2014). Direct-acting antiviral treatments with cure rates of 95 percent and higher have revolutionized hepatitis C care (Afdhal et al., 2014; Zoulim et al., 2015). Although there is no vaccine for HCV, secondary prevention measures can impede the spread of infection. In the United States, where most new HCV infections are associated with injection drug use, syringe exchange programs have particular promise to interrupt transmission (Mehta et al., 2011). Treatment of all chronic infections would do the same.
Yet this committee’s previous report concluded that while elimination of hepatitis B and C in the United States may be entirely feasible, it is not likely without meaningful changes to policy and directed research (Buckley and Strom, 2016; NASEM, 2016). Like a previous Institute of Medicine committee that commented on woefully underfunded surveillance systems and inadequate public spending on viral hepatitis prevention and treatment, this committee’s previous report discussed limitations with, among other things, surveillance, case detection, and access to care, as well as gaps in the current understanding of the viruses (IOM, 2010; NASEM, 2016). The report concluded that most of the barriers to preventing and treating viral hepatitis could be seen as consequences of another, more basic problem: viral hepatitis is not a public priority in the United States.
The United States is not alone in this, as the World Health Assembly resolution observed. The international movement toward eliminating hepatitis B and C as public health problems could help generate the impetus for change. A concrete action plan and clear goals could also do much to change attitudes domestically. The United States should not come late or halfheartedly to the global elimination effort. With this in mind, the Committee on a National Strategy for the Elimination of Hepatitis B and C issues this strategy document recommending actions that will hasten the end of HBV and HCV infections and deaths in the United States and advance the international goal of eliminating the public health problem of viral hepatitis by 2030.
The Centers for Disease Control and Prevention (CDC) and the Department of Health and Human Services (HHS) have a commitment to fighting viral hepatitis; the CDC Division of Viral Hepatitis and the HHS Office of Minority Health sponsored the first phase of this project. In phase two, the original sponsors were joined by the American Association for the Study of Liver Diseases, the CDC Division of Cancer Prevention and Control, the Infectious Diseases Society of America, and the National Viral Hepatitis Roundtable. Box 1-2 shows the statement of task for both phase one and two of this project, though this report is limited to the phase two task.
The Phase One Report
In the first phase of this project, the sponsors asked the committee whether it is feasible to eliminate hepatitis B and C from the United States. The first publication in this series briefly reviewed the literature on the
epidemiology and natural history of both infections.1 The committee then considered the feasibility of eliminating hepatitis B and C, dividing that question into smaller questions about ending transmission and reducing morbidity and mortality from chronic infection; for hepatitis C it also weighed the feasibility of eliminating chronic infection.
Part of the challenge of this task was first clarifying exactly what level of disease control could be considered elimination. Unlike eradication, which refers to a permanent, zero-level incidence of new infections without ongoing control measures, elimination is a softer target (CDC, 1993; Dowdle, 1998). CDC definitions of disease elimination emphasize cessation of transmission, and allow for circumstances where a disease may remain,
1 The committee encourages readers who are unfamiliar with the basic virology and natural history of these infections to consult the first report.
but its most devastating consequences avoided (e.g., trachoma remains, but with no further cases of blindness) (CDC, 1993). In this understanding, disease elimination can refer to a level of control where the disease is no longer considered a public health problem (CDC, 1993).
In considering the elimination of hepatitis B and C from the United States, it is important to remember that both infections are endemic abroad, making frequent importation of cases inevitable. Hepatitis C, though curable, is not vaccine-preventable. Chronic HBV infection, on the other hand, is incurable, but largely preventable with vaccination and prophylactic measures against vertical transmission. Antiviral treatment can reduce the risk of disease progression; there is no reason why people with chronic hepatitis B should not live long lives and die of unrelated causes. For these reasons, the committee concluded that, “hepatitis B and C could both be eliminated as public health problems in the United States, but that this would take considerable will and resources” (NASEM, 2016, p. 2). The report went on to define a public health problem as one that, “by virtue of transmission or morbidity or mortality commands attention as a major threat to the health of the community” (NASEM, 2016, p. 2). Tables 1-1 and 1-2 summarize the committee’s assessment of these questions, as well as critical factors relating to each step, and barriers to meeting the elimination goal.
This phase of the project builds off the conclusions of the phase one report. In this document, the committee has been asked to lay out appropriate goals for hepatitis reduction over time and specific actions to achieve them, being clear about possible barriers and ways to overcome them and articulating responsibilities for key stakeholders.
The Committee’s Approach to Its Charge
The committee met three times to prepare this report; see Appendix C. In closed session, the group evaluated the evidence and deliberated on the best strategy to eliminate hepatitis B and C as public health problems in the United States. Based on expert opinion and review of the evidence, the committee came to conclusions about a suitable strategy, recommending actions for specific organizations to reach this goal. The committee drew on published literature and presentations from expert speakers in its deliberations. Members of the public submitted written testimony to the committee (available from the National Academies of Sciences, Engineering, and Medicine’s Public Access Records Office, PARO@nas.edu).
The World Health Organization’s 2016 strategy document identified five areas in which action will be needed, referred to in the document as strategic directions. These five areas are meant to guide countries’ formation of their national strategies, each area addressing a set of essential questions (see Box 1-3). This report is organized around these five strate-
TABLE 1-1 The Feasibility of Eliminating Hepatitis B as a Public Health Problem in the United States with Critical Factors for Success and Crosscutting Problems
|Goal||Feasibility||Critical Factors||Crosscutting Barriers|
|Ending transmission||Perinatal||Highly feasible||
|Reducing morbidity and mortality attributable to ongoing infection||Slowing progression to cirrhosis Reducing deaths||Feasible||
NOTE: cccDNA = covalently closed circular DNA; HBV = hepatitis B virus.
SOURCE: NASEM, 2016.
TABLE 1-2 The Feasibility of Eliminating Hepatitis C as a Public Health Problem in the United States with Critical Factors for Success and Crosscutting Problems
|Goal||Feasibility||Critical Factors||Crosscutting Barriers|
|Eliminating chronic infection||Feasible||
|Reducing morbidity and mortality attributable to ongoing infection||Slowing progression to cirrhosis||Feasible||
NOTE: HCV = hepatitis C virus.
SOURCE: NASEM, 2016.
gic directions: information, interventions, service delivery, financing, and research. A separate chapter presents the results of commissioned models informing the committee’s goals on suitable targets, interim indicators, and a timeline for elimination in the United States.
The 2016 Annual Report to the Nation on the Status of Cancer celebrated continued declines in cancer deaths in the United States, attributing much of this progress to public health (Ryerson et al., 2016). Tobacco control measures have curbed the incidence of many cancers, especially lung cancer, long the most common and fatal cancer in the country (CDC, 2011; Henley et al., 2014; Jemal et al., 2008). Improved screening, early diagnosis, and treatment have contributed to declines in incidence and lengthened survival time for lung, colorectal, prostate, and breast cancers (Edwards
et al., 2010, 2014; Kohler et al., 2015; Ryerson et al., 2016). The recent annual report highlighted one troubling trend, however. The incidence of hepatocellular carcinoma, the most common form of primary liver cancer, increased 38 percent between 2003 and 2012, the most recent years for which data are available (Ryerson et al., 2016). Liver cancer deaths rose 56 percent in the same time, a sharper increase than that of any other cancer (Ryerson et al., 2016). Data from 2008 to 2012 indicate a disproportionate increase in racial and ethnic minorities: American Indian and Alaska Natives have the highest incidence of liver cancer (14.9 per 100,000), followed by Asian and Pacific Islanders (13.8 per 100,000) and Hispanics (12.7 per 100,000). Among non-Hispanic blacks, the age-specific rate of liver cancer has shifted over time and is now highest (around 60 per 100,000 people) at the relatively young ages of 55 to 59 (Ryerson et al., 2016). Another recent study confirmed the increase in hepatocellular carcinoma incidence,
especially among subgroups such as men aged 55 to 64, and highlighted geographic variation in the trend (White et al., 2016).
Hepatitis B and C are driving this increase. Together HBV and HCV account for about 80 percent of the world’s hepatocellular carcinoma (the most common form of liver cancer) (Arzumanyan et al., 2013).
Chronic hepatitis B increases odds of liver cancer 50 to 100 times, chronic hepatitis C by 15 to 20 times (El-Serag, 2012; Sherman and Llovet, 2011). Action against viral hepatitis is essential to combatting liver cancer. Box 1-4 describes Mongolia’s hepatitis elimination program in response to the country’s high rate of liver cancer mortality.
Much as public health measures have lessened the burden of lung, breast, colorectal, and prostate cancers over time, so can public health programs reverse troubling trends in liver cancer. This report outlines ways to reduce the burden of viral hepatitis in the United States and discusses the likely effects of such a reduction on the incidence of liver cancer and its frequent precursor, cirrhosis. The strategy of expanded screening and treatment, improved surveillance, harm reduction, adult vaccination, and ensured access to medicines would make hepatitis B and C rare diseases in the United States by 2030.
Abdel-Wahab, M. 1982. Schistosomiasis in Egypt. Boca Raton, FL: CRC Press.
Abdel-Wahab, M. F., G. T. Strickland, A. El-Sahly, L. Ahmed, S. Zakaria, N. El Kady, and S. Mahmoud. 1980. Schistosomiasis mansoni in an Egyptian village in the Nile Delta. American Journal of Tropical Medicine and Hygiene 29(5):868-874.
Afdhal, N., S. Zeuzem, P. Kwo, M. Chojkier, N. Gitlin, M. Puoti, M. Romero-Gomez, J. P. Zarski, K. Agarwal, P. Buggisch, G. R. Foster, N. Bräu, M. Buti, I. M. Jacobson, G. M. Subramanian, X. Ding, H. Mo, J. C. Yang, P. S. Pang, W. T. Symonds, J. G. McHutchison, A. J. Muir, A. Mangia, and P. Marcellin. 2014. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. New England Journal of Medicine 370(20):1889-1898.
Arzumanyan, A., H. M. Reis, and M. A. Feitelson. 2013. Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma. Nature Reviews Cancer 13(2):123-135.
Buckley, G. J., and B. L. Strom. 2016. What stands in the way of making hepatitis B and C rare diseases in the United States? Annals of Internal Medicine 165(4):284-285.
CDC (Centers for Disease Control and Prevention). 1993. Recommendations of the International Task Force for Disease Eradication. Morbidity and Mortality Weekly Report 42(RR-16). https://www.cdc.gov/mmwr/PDF/rr/rr4216.pdf (accessed February 24, 2017).
CDC. 2011. State-specific trends in lung cancer incidence and smoking—United States, 1999-2008. Morbidity and Mortality Weekly Report 60(36):1243-1247.
CDC. 2012. Progress toward prevention and control of hepatitis C virus—Egypt, 2001-2012. Morbidity and Mortality Weekly Report 61(29).
CDC. 2016. Viral hepatitis surveillance: United States, 2014. http://www.cdc.gov/hepatitis/statistics/2014surveillance/pdfs/2014hepsurveillancerpt.pdf (accessed Setpember 22, 2016).
Daily News Egypt. 2016a. All hepatitis C patients on waiting list now treated: Ministry of Health. July 28. http://www.dailynewsegypt.com/2016/07/28/hepatitis-c-patients-waiting-list-now-treated-ministry-health (accessed September 6, 2016).
Daily News Egypt. 2016b. State council rules for free treatment of hepatitis C patients. July 18. http://www.dailynewsegypt.com/2016/07/18/state-council-rules-for-free-treatment-of-hepatitis-c-patients (accessed September 6, 2016).
Dashdorj, N., B. Dashtseren, B. Bold, and D. Yagaanbuyant. 2014. P29: Epidemiological study of prevalence and risk factors for HBV among apparently healthy Mongolians. Journal of Viral Hepatitis 21(Suppl S2):38.
Dowdle, W. R. 1998. The principles of disease elimination and eradication. Bulletin of the World Health Organization 76(Suppl 2):22-25.
Edwards, B. K., E. Ward, B. A. Kohler, C. Eheman, A. G. Zauber, R. N. Anderson, A. Jemal, M. J. Schymura, I. Lansdorp-Vogelaar, L. C. Seeff, M. van Ballegooijen, S. L. Goede, and L. A. Ries. 2010. Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer 116(3):544-573.
Edwards, B. K., A. M. Noone, A. B. Mariotto, E. P. Simard, F. P. Boscoe, S. J. Henley, A. Jemal, H. Cho, R. N. Anderson, B. A. Kohler, C. R. Eheman, and E. M. Ward. 2014. Annual report to the nation on the status of cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer. Cancer 120(9):1290-1314.
Egyptian Ministry of Health and Population. 2014. Plan of action for the prevention, care & treatment of viral hepatitis, Egypt 2014-2018.
El-Serag, H. B. 2012. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 142(6):1264-1273 e1261.
Feld, J. J., K. V. Kowdley, E. Coakley, S. Sigal, D. R. Nelson, D. Crawford, O. Weiland, H. Aguilar, J. Xiong, T. Pilot-Matias, B. DaSilva-Tillmann, L. Larsen, T. Podsadecki, and B. Bernstein. 2014. Treatment of HCV with ABT-450/r–ombitasvir and dasabuvir with ribavirin. New England Journal of Medicine 370(17):1594-1603.
Gilead. 2015. Chronic hepatitis C treatment expansion: Generic manufacturing for developing countries. http://www.gilead.com/~/media/files/pdfs/other/hcv%20generic%20agreement%20fast%20facts%2072815.pdf (accessed September 15, 2016).
Gower, E., C. Estes, S. Blach, K. Razavi-Shearer, and H. Razavi. 2014. Global epidemiology and genotype distribution of the hepatitis C virus infection. Journal of Hepatology 61(1 Suppl):S45-S57.
Henley, S. J., T. B. Richards, J. M. Underwood, C. R. Eheman, M. Plescia, and T. A. McAfee. 2014. Lung cancer incidence trends among men and women—United States, 2005-2009. Morbidity and Mortality Weekly Report 63(1):1-5.
IOM (Institute of Medicine). 2010. Hepatitis and liver cancer: A national strategy for prevention and control of hepatitis B and C. Washington, DC: The National Academies Press.
Jemal, A., M. J. Thun, L. A. Ries, H. L. Howe, H. K. Weir, M. M. Center, E. Ward, X. C. Wu, C. Eheman, R. Anderson, U. A. Ajani, B. Kohler, and B. K. Edwards. 2008. Annual report to the nation on the status of cancer, 1975-2005, featuring trends in lung cancer, tobacco use, and tobacco control. Journal of the National Cancer Institute 100(23):1672-1694.
Kandeel, A., M. Genedy, S. El-Refai, A. L. Funk, A. Fontanet, and M. Talaat. 2016. The prevalence of hepatitis C virus infection in Egypt 2015: Implications for future policy on prevention and treatment. Liver International 37(1):45-53.
Kohler, B. A., R. L. Sherman, N. Howlader, A. Jemal, A. B. Ryerson, K. A. Henry, F. P. Boscoe, K. A. Cronin, A. Lake, A. M. Noone, S. J. Henley, C. R. Eheman, R. N. Anderson, and L. Penberthy. 2015. Annual report to the nation on the status of cancer, 1975-2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. Journal of the National Cancer Institute 107(6):791-797.
Ly, K. N., J. Xing, R. M. Klevens, R. B. Jiles, J. W. Ward, and S. D. Holmberg. 2012. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Annals of Internal Medicine 156(4):271-278.
Mast, E. E., H. S. Margolis, A. E. Fiore, E. W. Brink, S. T. Goldstein, S. A. Wang, L. A. Moyer, B. P. Bell, and M. J. Alter. 2005. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Part 1: Immunization of infants, children, and adolescents. Morbidity and Mortality Weekly Report 54(RR-16):1-31.
McNeil, D. G., Jr. 2015. Curing hepatitis C, in an experiment the size of Egypt. New York Times, December 25. http://www.nytimes.com/2015/12/16/health/hepatitis-c-treatment-egypt.html?_r=0 (accessed October 26, 2016).
Mehta, S. H., J. Astemborski, G. D. Kirk, S. A. Strathdee, K. E. Nelson, D. Vlahov, and D. L. Thomas. 2011. Changes in blood-borne infection risk among injection drug users. Journal of Infectious Diseases 203(5):587-594.
Mongolia WHO (World Health Organization) Representative Office. 2010. WHO country cooperation strategy for Mongolia 2010-2015. Geneva, Switzerland: WHO, Western Pacific Region.
NASEM (National Academies of Sciences, Engineering, and Medicine). 2016. Eliminating the public health problem of hepatitis B and C in the United States: Phase one report. Washington, DC: The National Academies Press.
Nelson, N. P., T. V. Murphy, and D. J. Jamieson. 2014. Prevention of perinatal hepatitis B virus transmission. Journal of the Pediatric Infectious Diseases Society 3(Suppl 1):S7-S12.
Ryerson, A. B., C. R. Eheman, S. F. Altekruse, J. W. Ward, A. Jemal, R. L. Sherman, S. J. Henley, D. Holtzman, A. Lake, A. Noone, R. N. Anderson, J. Ma, K. N. Ly, K. A. Cronin, L. Penberthy, and B. A. Kohler. 2016. Annual report to the nation on the status of cancer, 1975-2012, featuring the increasing incidence of liver cancer. Cancer 122(9):1312-1337.
Sherman, M., and J. M. Llovet. 2011. Smoking, hepatitis B virus infection, and development of hepatocellular carcinoma. Journal of the National Cancer Institute 103(22):1642-1643.
Stanaway, J. D., A. D. Flaxman, M. Naghavi, C. Fitzmaurice, T. Vos, I. Abubakar, L. J. Abu-Raddad, R. Assadi, N. Bhala, B. Cowie, M. H. Forouzanfour, J. Groeger, K. M. Hanafiah, K. H. Jacobsen, S. L. James, J. MacLachlan, R. Malekzadeh, N. K. Martin, A. A. Mokdad, A. H. Mokdad, C. J. L. Murray, D. Plass, S. Rana, D. B. Rein, J. H. Richardus, J. Sanabria, M. Saylan, S. Shahraz, S. So, V. V. Vlassov, E. Weiderpass, S. T. Wiersma, M. Younis, C. Yu, M. El Sayed Zaki, and G. S. Cooke. 2016. The global burden of viral hepatitis from 1990 to 2013: Findings from the Global Burden of Disease Study 2013. Lancet 388(10049):1081-1088.
Strickland, G. T. 2006. Liver disease in Egypt: Hepatitis C superseded schistosomiasis as a result of iatrogenic and biological factors. Hepatology 43(5):915-922.
Thomas, D. L. 2013. Global control of hepatitis C: Where challenge meets opportunity. Nature Medicine 19(7):850-858.
White, D. L., A. P. Thrift, F. Kanwal, J. Davila, and H. B. El-Serag. 2016. Incidence of hepatocellular carcinoma in all 50 United States, from 2000 through 2012. Gastroenterology 152(4):812-820.e5.
WHO (World Health Organization). 2015. Hepatitis B. http://www.who.int/mediacentre/factsheets/fs204/en (accessed July 22, 2016).
WHO. 2016a. Global health sector strategy on viral hepatitis, 2016-2021: Towards ending viral hepatitis. Geneva, Switzerland: WHO. http://apps.who.int/iris/bitstream/10665/246177/1/WHO-HIV-2016.06-eng.pdf (accessed July 19, 2016).
WHO. 2016b. Schistosomiasis: Fact sheet. http://www.who.int/mediacentre/factsheets/fs115/en (accessed December 30, 2016).
WHO and Center for Disease Analysis. 2015. Public health and economic impact of a population based approach to HCV treatment in Mongolia. WHO, Center for Disease Analysis.
WHO Regional Office for the Western Pacific. 2014. Meeting report. Technical meeting on raising awareness, surveillance, prevention and management of viral hepatitis in Mongolia. Manila, Philippines: WHO Regional Office for the Western Pacific.
WHO Regional Office for the Western Pacific. 2015. Viral hepatitis in Mongolia: Situation and response. Geneva, Switzerland: WHO.
WHO Regional Office for the Western Pacific. n.d. Hepatitis: A crisis in Mongolia. http://www.wpro.who.int/hepatitis/resource/features/mongolia_story/en (accessed June 30, 2016).
Wiktor, S. Z., and Y. J. F. Hutin. 2016. The global burden of viral hepatitis: Better estimates to guide hepatitis elimination efforts. The Lancet 388(10049):1030-1031.
Zoulim, F., T. J. Liang, A. L. Gerbes, A. Aghemo, S. Deuffic-Burban, G. Dusheiko, M. W. Fried, S. Pol, J. K. Rockstroh, N. A. Terrault, and S. Wiktor. 2015. Hepatitis C virus treatment in the real world: Optimising treatment and access to therapies. Gut 64(11):1824-1833.