Viral Hepatitis Surveillance in the United States: Then,Now,and Looking Forward

Abstract

Keywords

viral hepatitis surveillance data modernization trends public health

Despite vaccines that can prevent hepatitis A and hepatitis B and treatment that can cure hepatitis C, more than 86 000 acute hepatitis virus infections were estimated to have occurred and nearly 13 000 viral hepatitis–related deaths were reported in the United States in 2023.¹ During January 2017–March 2020, an estimated 660 000 adults had hepatitis B and 2.2 million adults had hepatitis C.^2-4 Surveillance systems compile data to produce disease estimates, supporting public health programs, policies, and decisions. A trained and experienced workforce, integrated surveillance systems, and quality data are essential for understanding the epidemiology of viral hepatitis and for developing and evaluating prevention efforts, policies, and programs. These attributes are essential for meeting the US Department of Health and Human Services and Centers for Disease Control and Prevention (CDC) goals of eliminating viral hepatitis as a public health threat by 2030.^5-7

Surveillance involves collecting, analyzing, and disseminating data that quantify the incidence and prevalence of disease and associated deaths; identifying populations at risk; documenting behaviors and other factors that increase or decrease risk; monitoring medical care and treatment; and characterizing access to treatment and care.⁸ This commentary describes the history, current status, and future of national viral hepatitis surveillance, focusing on 3 core systems: (1) the National Notifiable Diseases Surveillance System (NNDSS), which captures information on reported cases from state and territorial health departments; (2) the National Health and Nutrition Examination Survey (NHANES), which provides survey and seroprevalence data among a representative sample of the US population; and (3) the National Vital Statistics System (NVSS), which provides mortality data based on death certificates issued by state governments. Other sources of data are discussed elsewhere in this supplemental issue of Public Health Reports.^9-11

Impact of the Discovery of Hepatitis A, Hepatitis B, and Hepatitis C Viruses on Surveillance

Viral hepatitis surveillance in the United States predated the discovery of any hepatitis virus. Jaundice, a symptom of hepatitis, has been recognized, monitored, and reported for millennia.^12-14 During the 17th century through the mid–20th century, outbreaks in community or military settings were described as “epidemic jaundice” or “infectious hepatitis.”¹⁵ Outbreaks associated with injection or transfusion were called “serum hepatitis.”^16-18 Codes, used to track diagnoses and procedures occurring in medical facilities, included hepatitis for the first time in 1949 in the sixth revision of the International Classification of Diseases (ICD).¹⁹

In 1963, Blumberg discovered a particle, the Australian antigen, in the sera of an indigenous Australian and in US patients with hemophilia.^20,21 In 1971, the Australian antigen was determined to be the hepatitis B virus (HBV) surface antigen (HBsAg), and the HBV core antigen was identified shortly thereafter.^22-24 These discoveries ignited intense efforts to identify viral causes of hepatitis in the absence of HBV. The designation of serum hepatitis as hepatitis B and evidence of a different viral etiology by visualization of viral particles in the stool of patients with infectious hepatitis led to the identification and reporting of hepatitis A virus in 1973.²⁵ For about 15 years (ie, 1973-1989) until hepatitis C was discovered, transmittable hepatitis that was not identified as hepatitis A or hepatitis B was referred to as non-A, non-B hepatitis. In 1989, hepatitis C virus (HCV) was discovered by Houghton²⁵ based on earlier works by Alter and colleagues²⁶ and Feinstone et al.²⁷ Changes in the definition and presentation of viral hepatitis cases in weekly and annual case surveillance summaries, mortality reports, and national survey data reflect the discovery of the viruses, advances in laboratory testing, and evolving surveillance practices (eTable 1a in Supplemental Material).

NNDSS

The NNDSS is CDC’s case-based passive surveillance system used by states to voluntarily report cases of viral hepatitis and more than 120 diseases and conditions to CDC.²⁸ NNDSS is based on case identification using laboratory results, health care providers’ diagnoses, standard case definitions to ensure consistency and validity of case classification across jurisdictions, and a standardized case report form to ensure collection of a uniform set of demographic, laboratory, and risk behavior and exposure information. CDC partners with the Council of State and Territorial Epidemiologists to determine which diseases and conditions should be included on the list of nationally notifiable conditions and to develop case definitions for these diseases.^29-31 The Council of State and Territorial Epidemiologists, in collaboration with CDC, works with state epidemiologists and program staff to develop position statements and establish clinical, laboratory, and epidemiologic criteria for case ascertainment and classification.²⁹ The criteria outlined in the position statements are used to standardize surveillance case definitions.³² Each state determines which notifiable diseases and conditions will be reportable in its jurisdiction.

ICD codes were used to classify notifiable conditions prior to the development of specific surveillance case definitions; thus, state health departments and physicians used nonuniform criteria to classify and report viral hepatitis cases.^19,33 Infectious hepatitis officially became a nationally notifiable disease in 1952.^33,34 Two types of hepatitis were evident based on differences in symptom onset, course, and transmissibility. Serum hepatitis was added as a separate disease in 1953, and this dual classification continued through 1971. Classification of viral hepatitides reported as distinct nationally notifiable diseases began for hepatitis A and hepatitis B in 1973; non-A, non-B hepatitis in 1982-2002; perinatal hepatitis B in 1995; acute hepatitis C in 1994 (with non-A, non-B through 2002); chronic hepatitis B and chronic hepatitis C in 2003; and perinatal hepatitis C in 2018 (eTable 1a in Supplemental Material). Changes in case definitions are required to accommodate changes in the understanding of disease course, updates to laboratory testing, and when new diseases are recognized and added to the list of notifiable diseases. For example, recognition of 2 forms of hepatitis B led to separate case definitions for acute and chronic hepatitis B.³⁵

Case identification begins when state, local, or territorial health departments receive a clinical or laboratory report consistent with the criteria in a viral hepatitis case definition. Information about signs and symptoms, risk behavior and exposure, and potential contacts is obtained by contacting health care providers and/or the diagnosed patient. Cases are investigated to collect relevant information at the state, local, or territorial health department level. State and territorial health departments voluntarily submit a standard set of information about each identified case to CDC through NNDSS. CDC processes and compiles the data and publishes weekly tables and annual viral hepatitis surveillance reports.^1,36 The types of information included in viral hepatitis surveillance reports have varied, consistent with reporting requirements, and the ability to obtain information from health care providers and/or patients (eTable 1b in Supplemental Material). CDC, health departments, and other external partners use the data to monitor incidence and to design, implement, and evaluate prevention programs and policies.^37,38

Incremental Expansion of US Viral Hepatitis Surveillance

Limitations of NNDSS include incomplete data, serologic test results that are inconsistent with the case definition, challenges in applying the case definition appropriately, and underreporting of cases. To address the completeness of data, viral hepatitis surveillance activities have focused on follow-up with health care providers and/or patients to obtain complete demographic, risk behavior, and exposure data and have used other data sources to supplement case information. Online training is available to improve understanding and application of serologic test results and accuracy in applying case definitions.³⁹ In 2021, CDC published “Viral Hepatitis Surveillance and Case Management: Guidance for State, Territorial, and Local Health Departments,” which included detailed information to guide the application of case definitions and a list of databases that are useful for supplementing case surveillance data.⁴⁰ One reason for the underreporting of cases was the requirement for symptoms, which were infrequently documented, to meet the case definitions for acute hepatitis B and acute hepatitis C. In 2014, CDC published adjustment factors to account for underascertainment and underreporting of cases of acute hepatitis A, acute hepatitis B, and acute hepatitis C, to be able to estimate the number of annual infections (symptomatic and asymptomatic) based on the number of reported cases.⁴¹

Beginning in 1982, CDC initiated and funded several demonstration projects to strengthen viral hepatitis surveillance and collect better quality data. Sentinel Counties for the Study of Viral Hepatitis (1982-2006), the first of these initiatives, funded 6 US counties to improve understanding of acute viral hepatitis, patterns of disease transmission, risk factors, and effects of prevention programs.^42-44 During 2006-2012, the Emerging Infections Program funded 8 state and 1 city health department to conduct enhanced surveillance of chronic hepatitis B and chronic hepatitis C.⁴⁵ The Enhanced Surveillance Program (2012-2016) supported 5 states and 2 cities to improve surveillance for acute and chronic hepatitis B and hepatitis C.^46-49 Fourteen states that had a high incidence of acute hepatitis B and hepatitis C were funded during 2017-2021 to improve surveillance and implement prevention services, including testing and treatment. Beginning in 2021, CDC’s Integrated Viral Hepatitis Surveillance and Prevention cooperative agreement funded 49 states, 8 large cities/local jurisdictions, the District of Columbia, and Puerto Rico.⁵⁰ The purpose of the Integrated Viral Hepatitis Surveillance and Prevention cooperative agreement was to support activities and strategies necessary for monitoring progress toward achieving goals outlined in the CDC Division of Viral Hepatitis’s 2025 Strategic Plan. The plan includes developing outbreak response plans; producing and disseminating more complete surveillance data to guide development, implementation, and evaluation of prevention and risk-reduction programs and policies; improving testing, linkage to care, and treatment; and building longitudinal surveillance registries.

In 2020, as a part of the Data Modernization Initiative, CDC funded health departments to advance jurisdictional surveillance systems and foster more complete, timely, and integrated surveillance data for public health action. These overall enhancements will also improve viral hepatitis–specific surveillance.⁵¹ In support of molecular surveillance, CDC developed the Global Hepatitis Outbreak and Surveillance Technology (GHOST), which used next-generation sequencing and computational bioinformatics analysis during the national hepatitis A outbreak of 2016 through 2023, to determine the genetic relatedness of hepatitis A case strains and provide confirmation of multistate outbreaks using molecular epidemiology.^52,53 In addition, GHOST analysis allowed identification of hepatitis C transmission networks and the detection of viral genetic relatedness within networks.^54,55 In 2023, CDC funded 2 jurisdictions to pilot the integration of GHOST computational bioinformatics with epidemiological surveillance for outbreak detection and response.

NHANES

NHANES is a series of cross-sectional surveys of a representative sample of the US civilian, noninstitutionalized population conducted by CDC’s National Center for Health Statistics since 1959.⁵⁶ The survey became continuous, with 2-year data collection cycles, in 1999.⁵⁶ NHANES collects information about disease prevalence, sociodemographic and housing characteristics, and health-related exposures and behaviors through interviews and physical and clinical examinations of selected people. Clinical examinations include collection and laboratory testing of biological samples.⁵⁶ NHANES II (1976-1980) included laboratory tests for hepatitis A antibody, hepatitis B core antibody, hepatitis B surface antibody, and hepatitis B surface antigen⁵⁷ (eTable 2 in Supplemental Material). Testing for hepatitis C was added with NHANES III in 1988-1994.⁵⁸ Prevalence estimates for hepatitis B and hepatitis C using these data have been widely published.^2-4 Survey questions about hepatitis A and hepatitis B vaccinations have been included since 1999. The 2001-2012 surveys included a hepatitis C follow-up questionnaire to assess prior knowledge of viral hepatitis status and viral hepatitis causes and transmission.⁵⁹ Beginning in 2013, before receiving results of their NHANES hepatitis tests, participants were asked if they had ever been told they had hepatitis B or hepatitis C, and, if so, if they had ever been treated for their disease.^2,4 Questions about hepatitis A vaccination and awareness of hepatitis B status were the only viral hepatitis–related questions included in the August 2021–August 2023 cycle.⁶⁰

NHANES is the only source available to provide nationally representative data for laboratory markers of viral hepatitis, along with extensive data on race and Hispanic origin, other health conditions, risk exposures, and behaviors. NHANES viral hepatitis–related data are used alone or in combination with other data to estimate population prevalence of susceptibility and immunity for hepatitis A and hepatitis B, current infection with hepatitis B and hepatitis C, clearance of HCV infection, and awareness of HBV infection.^2,4,5,7,59

NVSS

Mortality data from NVSS are used to determine the number of deaths for which viral hepatitis is listed as an underlying or contributing cause.⁶¹ Most people who are infected with viral hepatitis are asymptomatic, and the case fatality rate for acute viral hepatitis is relatively low.^62,63 However, if left untreated when they do not spontaneously clear, chronic hepatitis B and hepatitis C may silently progress to cirrhosis, hepatocellular carcinoma, and premature death, years after the initial infection.

NVSS compiles data on deaths registered in all 50 states; Washington, DC; and the US territories. Since 1999, the 10th revision of the ICD has been used to code and classify causes of death.⁶⁴ Summary tables of viral hepatitis–related mortality used only underlying cause of death before 1999 and changed to using multiple causes of death data, including contributing causes, in 1999 (eTable 3 in Supplemental Material). Beginning in 2009, the inclusion of hepatitis A, hepatitis B, and hepatitis C mortality data in CDC’s annual hepatitis surveillance report provided a useful context for understanding trends in viral hepatitis–related deaths.¹

NVSS standards ensure highly complete data. However, studies conducted among patients in a large health care system found that hepatitis B and hepatitis C were not listed on the death certificate among some decedents known to have viral hepatitis disease and whose cause of death was liver related.^65-67 Monitoring deaths related to viral hepatitis is crucial because each premature death represents a missed opportunity for treatment and, for hepatitis C, cure, and signifies a failure somewhere along the care continuum.

Assessment of mortality data showed an increase in hepatitis C–related deaths from 1999 through 2013, and despite a decrease during 2016-2017, HCV mortality remained high in certain regions and among certain populations.^68,69 More recently, mortality data were used to show how increased vaccination among adults shifted the epidemiologic picture of hepatitis A mortality.⁵³ Local jurisdictions can enhance public health efforts by matching viral hepatitis mortality data with surveillance and registry data. Doing so allows the identification of cases missed by surveillance, providing better estimates of disease prevalence, enabling a close-out of follow-up if it is likely the person is deceased, and decreasing the cost of investigations.⁷⁰ The analysis of mortality data as a stand-alone data source can identify geographic areas and sociodemographic populations with the highest viral hepatitis mortality rates, thereby informing where public health efforts could be prioritized.^53,69,70

Public Health Implications

During the past 6 decades, viral hepatitis surveillance has matured into a network of systems that provide a comprehensive view of the epidemiology of viral hepatitis. The 3 core systems are essential to understanding epidemiology, identifying gaps in data, and increasing our understanding of viral hepatitis at the national, state, and local levels. These data are used to inform and enhance prevention activities and programs. Data from NNDSS provide estimates of new viral hepatitis cases, but because of underascertainment and underreporting, adjustment factors are typically applied to better estimate incidence. Also, risk exposure and behavior information are limited in these data.⁴² NHANES provides estimates of national prevalence and, with data from other sources and application of complex statistical analyses, can produce state estimates of prevalence.⁷¹ However, populations at high risk of hepatitis are not included in the NHANES sampling frame. Mortality data from the NVSS include all deaths among US residents but may underestimate the magnitude of hepatitis-related deaths because of misclassification and underreporting.^65-67 Supplementing these core data with other sources will improve the contextual understanding of viral hepatitis incidence, prevalence, and mortality in the United States.

Surveillance is at the core of public health practice. Surveillance data are used to monitor progress toward eliminating the public health threat of viral hepatitis in the United States. Numerous activities are being implemented to improve the quality and expand the usefulness of viral hepatitis surveillance data. These activities include providing financial support to improve systems in jurisdictions, expanding the use of other systems and sources to supplement case data, including molecular data such as viral genomics, and modernizing the data system. Using complementary data sources can provide additional information that improves our understanding of the spectrum of viral hepatitis disease, inform prevention efforts, and enhance the monitoring of elimination progress.

Supplemental Material

sj-docx-1-phr-10.1177_00333549251397367 – Supplemental material for Viral Hepatitis Surveillance in the United States: Then, Now, and Looking Forward

Supplemental material, sj-docx-1-phr-10.1177_00333549251397367 for Viral Hepatitis Surveillance in the United States: Then, Now, and Looking Forward by Ruth B. Jiles, Laurie K. Barker, Kathleen N. Ly, Noreen Kloc and Alfred DeMaria in Public Health Reports®

Footnotes

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Disclaimer

The findings and conclusions in this article are those of the authors and do not necessarily reflect the official position of the Centers for Disease Control and Prevention.

ORCID iDs

Ruth B. Jiles, PhD, MPH, MS

Laurie K. Barker, MSPH

Kathleen N. Ly, MPH

Noreen Kloc, MPH

Alfred DeMaria Jr, MD

Supplemental Material

Supplemental material for this article is available online. The authors have provided these supplemental materials to give readers additional information about their work. These materials have not been edited or formatted by Public Health Reports’s scientific editors and, thus, may not conform to the guidelines of the AMA Manual of Style, 11th Edition.

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