The National Academy Report on the Elimination of Viral Hepatitis: An Infectious Disease Physician’s Perspective

Summary

Hepatitis B and C viruses are leading causes of liver disease. The United States should engage in a coordinated effort to eliminate viral hepatitis as a public health problem, which requires special attention to populations often seen by infectious disease clinicians.

Imagine rounds in your hospital in 2047: A 52-year-old man has been transferred from a rural hospital after presenting with a first episode of ascites and encephalopathy—a new diagnosis of cirrhosis. His medical record reveals repair of his anterior cruciate ligament in 2015. A period of prescription opioid abuse was followed by intravenous heroin, leading to admission to a detoxification facility in 2017. Since that time, he has remained abstinent of illicit drugs. He requires a liver transplant, at a time when he is assisting his aging parents and paying for his first child’s college tuition. He is diagnosed with hepatitis C virus (HCV); the medical student is shocked as he thought that this virus was eliminated as a problem in the United States.

The medical student asks you, “What happened?”

Returning to the current day, late presentations of HCV-related cirrhosis have occurred with regularity over the last 2 decades. A peak of incidence occurred during the 1960s–1980s, resulting in millions of Americans infected with HCV. As the infection takes decades to progress to cirrhosis, it currently kills more people in the United States than human immunodeficiency virus (HIV), tuberculosis, and 58 other infections combined [1]. HCV is the primary reason for liver transplantation and drives the rising incidence of hepatocellular carcinoma [2].

Coinciding with this rise in morbidity and mortality, an expansive opioid epidemic has resulted in a marked increase of injection-related complications. Overdose is the most immediate threat, but a new wave of HCV infections is occurring among people who inject drugs (PWID), with about 30000 (range, 24200–104200) new infections in Americans yearly [3]. In addition to HCV, outbreaks of hepatitis B virus (HBV) [4] and HIV [5] highlight the costly consequences of not providing preventive services.

The impact of novel therapeutics is currently limited as only a fraction of persons living with HCV are identified and a smaller fraction linked to care; even if linked, patients are often denied safe, effective, and curative therapies [6]. As most transmission is silent and chronic infection takes decades until cirrhosis, we may have been lulled into complacency; however, the current burden mandates a renewed sense of urgency.

A PATH TO ELIMINATION

On 28 March 2017, the Institute of Medicine completed a 2-part report containing recommendations for a National Strategy for the Elimination of HBV and HCV [2, 7]. The panel’s report does not set out to achieve complete eradication of these 2 infections, as pursued for smallpox, polio, and guinea worm, but aims for a goal of elimination of the public health problem. A public health problem was defined as one “that by virtue of transmission or morbidity or mortality commands attention as a major threat to the health of the community” [2]. This ambitious goal will require significant efforts to prevent new transmissions, diagnose millions of infections, link them to care, and provide access to treatment. Elimination projects in places such as Mongolia and the Republic of Georgia are occurring as components of a World Health Organization global elimination campaign targeting the year 2030; the report explores whether and how the United States can feasibly join other countries in achieving these goals [8].

For the elimination of the public health problem of viral hepatitis, there are 2 major burdens that require attention: new transmissions and liver-related complications. For HBV, the report target is to avert >60000 deaths due to related complications. For reducing incidence of HBV, universal vaccination, a strategy used in the campaigns to eliminate polio and smallpox, is the backbone. Unlike those infections, HBV transmission is silent and may establish long-term infection. Ending transmission of HBV is highly feasible with attention to vaccination and screening of pregnant women.

For HCV, the report’s model targets a 90% reduction in incident infections and a two-thirds reduction in HCV-related deaths by 2030. There is no proven vaccine, so prevention relies on reduction in risky behavior, best accomplished by education, addressing drug addiction, and decreasing the population able to transmit. The strategy to reduce HCV incidence therefore parallels the campaigns to eliminate guinea worm (education) or onchocerciasis (drug treatment). Scale-up of both prevention and treatment would be most effective, as harm reduction could prevent new infections (and reinfections) while antivirals cure the vast majority of persons living with HCV infection [9].

The proposed pathways to elimination in the United States contain several themes (Table 1) [7]. First, there must be expansion of access to prevention, via adult HBV vaccination and attention to hepatitis B surface antigen (HBsAg)–positive mothers, and, for PWID, syringe exchange and/or opioid agonist therapy. Second, screening must be expanded, incidence measured, and surveillance augmented to identify cases and measure public health responses. Third, barriers to treatment must be removed. Several solutions are proposed to expand capacity (eg, recruitment of primary care physicians, a Ryan White–like effort) and bring these interventions to needy populations (eg, prisoners). Finally, the effort must be coordinated nationally to augment surveillance, set research priorities, and build capacity.

Table 1.

Recommendations of the Phase 2 Report Regarding the National Strategy for the Elimination of Hepatitis B and C

Recommendation 2-1: The highest level of the federal government should oversee a coordinated effort to manage viral hepatitis elimination.

Recommendation 3-1: The CDC, in partnership with state and local health departments, should support standard hepatitis case finding measures and the follow-up and monitoring of all viral hepatitis cases reported through public health surveillance. CDC should work with the National Cancer Institute to attach viral etiology to reports of liver cancer in its periodic national reports on cancer.

Recommendation 3-2: The CDC should support cross-sectional and cohort studies to measure HBV and HCV infection incidence and prevalence in high-risk populations.

Recommendation 4-1: States should expand access to adult hepatitis B vaccination, removing barriers to free immunization in pharmacies and other easily accessible settings.

Recommendation 4-2: The CDC, the AASLD, the IDSA, and the ACOG should recommend that all HBsAg-positive pregnant women have early prenatal HBV DNA and liver enzyme tests to evaluate whether antiviral therapy is indicated for prophylaxis to eliminate mother-to-child transmission or treatment of chronic active hepatitis.

Recommendation 4-3: States and federal agencies should expand access to syringe exchange and opioid agonist therapy in accessible venues.

Recommendation 4-4: The CDC should work with states to identify settings appropriate for enhanced viral hepatitis testing based on expected prevalence.

Recommendation 4-5: Public and private health plans should remove restrictions that are not medically indicated and offer direct-acting antivirals to all patients with chronic hepatitis C.

Recommendation 5-1: The National Committee for Quality Assurance should establish measures to monitor compliance with viral hepatitis screening guidelines and hepatitis B vaccine birth dose coverage and include the new measures in the Healthcare Effectiveness Data and Information Set.

Recommendation 5-2: The AASLD and the IDSA should partner with primary care providers and their professional organizations to build capacity to treat hepatitis B and C in primary care. The program should set up referral systems for medically complex patients.

Recommendation 5-3: The DHHS should work with states to build a comprehensive system of care and support for special populations with hepatitis B and C on the scale of the Ryan White system.

Recommendation 5-4: The criminal justice system should screen, vaccinate, and treat hepatitis B and C in correctional facilities according to national clinical practice guidelines.

Recommendation 6-1: The federal government, on behalf of the DHHS, should purchase the rights to a direct-acting antiviral for use in neglected market segments, such as Medicaid, the Indian Health Service, and prisons. This could be done through the licensing or assigning of a patent in a voluntary transaction with an innovator pharmaceutical company.

Abbreviations: AASLD, American Association for the Study of Liver Diseases; ACOG, American College of Obstetricians and Gynecologists; CDC, Centers for Disease Control and Prevention; DHHS, US Department of Health and Human Services; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; IDSA, Infectious Diseases Society of America.

Such effort will come with upfront cost and, from a “birds-eye” point of view, will save society in the long term the future costs of treating new infections and caring for end-stage liver disease [10]. This societal point of view is not easily taken by individual organizations or payors when facing the high upfront costs of screening, evaluation, and treatment. Part of a “win-win” solution for society requires decreased costs of antivirals; this may occur via decreased treatment durations, competition between drug makers, and negotiations.

HOW CAN INFECTIOUS DISEASE PHYSICIANS WORK TOWARD ELIMINATION?

Along with obstetricians, pharmacists, hepatologists, and primary care physicians, we will be at the forefront of implementing several of the recommendations, including aggressive case finding via expanded screening, applying HBV vaccination, and provision of preventive measures to the populations we serve. Whether it is the inpatient with an injection-related soft tissue infection, the outpatient seeking sexually transmitted disease testing, or the immigrant/refugee, we will have numerous opportunities to address the prevention and identification of viral hepatitis.

Through expanding our capacity for antiviral treatment, we would help reduce the burden of these infections and associated liver disease. For higher-risk groups, we can apply the lessons learned from HIV regarding expanded screening, retaining patients in care, and maximizing adherence. Moreover, we can join hepatologists to educate and train our primary care colleagues, a specific recommendation to expand treatment capacity (Table 1). Many hands make light work.

We can also advocate for those living with viral hepatitis. Many of us continue to fight against the stigma associated with HIV; similarly, we may combat stigma that comes with these infections. Disadvantaged populations are less likely to access HCV therapy [11], an unjust disparity. The response to viral hepatitis simply has not garnered enough resources. HCV kills far more people and produces a similar number of new infections in the United States, yet viral hepatitis garners 1/30th the federal funding given to combat HIV [12]. As we did for HIV, we can bring attention to stigmatized populations who suffer from inadequate responses to their needs and unfair policies and practices.

We will need to carve out time, the scarcest of resources. The response to viral hepatitis detailed in the report requires us to send case reports to departments of public health, to counsel patients undergoing screening, to educate colleagues, and to fill out lengthy prior authorization forms; all events that are not well reimbursed. Our primary care colleagues may find these quite burdensome. Even a Ryan White–like effort would be unlikely to cover all aspects of viral hepatitis outreach, care and counseling, while needing to overcome cultural and geographic barriers. Thus far, informing patients after antiviral treatment for HCV that they are cured of HCV is extremely rewarding; how to deliver the care needed to achieve these conversations on a mass scale requires more attention.

Finally, we will work as part of a team. Elimination will only be achieved as providers work in conjunction with researchers, policymakers, the pharmaceutical industry, and the community.

CONCLUSIONS

HBV and HCV are leading causes of liver disease and mortality in the United States and around the world [8]. A therapeutic revolution has produced safe and effective antiviral treatments for both viruses, and our toolbox to prevent and combat these infections is significant. We can imagine 2 futures before us: one in which the recommendations are implemented and another in which they are ignored. If implemented, the future would make the above case presentation the so-called “zebra.” If ignored or even delayed, the above case may be too common in 2047. The time to act was yesterday—as we cannot turn back the clock, we can only act today to implement a coordinated, collaborative, and creative effort to eliminate viral hepatitis.

Notes

Acknowledgments. A. Y. K. is funded by the National Institutes of Health and the Patient-Centered Outcomes Research Institute.

Potential conflicts of interest. Author certifies no potential conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.