Viral hepatitis elimination requires equitable public health approach
Viral hepatitis is a major danger to public health. According to WHO’s 2024 Global Hepatitis Report, viral hepatitis deaths increased from 1.1 million in 2019 to 1.3 million in 2022, rates now similar to tuberculosis.
Hepatitis B virus caused 83% of these deaths and hepatitis C virus 17%. Health disparities contribute to the persistence of viral hepatitis. High-impact interventions to prevent, diagnose and treat viral hepatitis exist, including vaccines and effective treatments for HBV and a cure for HCV. The COVID-19 pandemic further exposed the health disparities and inequities faced by underserved populations. To achieve viral hepatitis elimination, these inequities need to be faced head on.
WHO has defined viral hepatitis elimination as a 90% reduction in new chronic infections and a 65% reduction in mortality when compared with 2015 baseline data. The most common hepatitis viruses with the greatest impact on public health are A, B, and C. HAV is the most common cause of acute viral hepatitis, with infection incidence strongly correlated to poor sanitation: Over 50% of all outbreaks are traced back to improper food handling and low socioeconomic conditions.
HBV and HCV transmission can occur perinatally, through sexual contact or through injection use. An estimated 254 million people are living with HBV and 50 million with HCV. Bangladesh, China, Ethiopia, India, Indonesia, Nigeria, Pakistan, the Philippines, Russia and Vietnam, collectively, shoulder nearly two-thirds of the global burden of HBV and HCV. In the United States, non-Hispanic Black people had the highest rate of acute HBV infection in 2022. Historically, people aged 30 to 59 years and men have had the highest rates of acute HBV infection. Chronic HBV infection followed a similar pattern of disparities, with highest rates of infection among non-Hispanic Asian/Pacific Islander people. Since 2010, those aged 20 to 49 years have consistently had the highest rates of acute HCV infection, mirroring fatal overdose data in the U.S. This underscores the need for targeted interventions across racial and ethnic populations, age groups and genders.
Prevention through vaccination
One challenge hindering the lack of progress toward elimination of viral hepatitis is missed opportunities for vaccination. Safe and effective vaccines to prevent HAV and HBV are available. In 2011, the first vaccine to prevent hepatitis E infection was approved in China. HAV vaccines have been available for over 2 decades for those aged 12 months or older. Safe drinking water, sanitation and hygiene and outbreak control are other important HAV infection mitigation measures. In highly endemic countries, most are asymptomatically infected with HAV in childhood, which yields immunity in adulthood. HAV vaccination is not recommended in these countries because it may cause a “paradoxical increase in disease incidence in unvaccinated people,” according to WHO. In more developed HAV countries, outbreaks among men who have sex with men and people experiencing homelessness have contributed to subsequent vaccine shortages, given the sharp increases in vaccine demands. Bolstering vaccine supply stores, prevaccination screening for anti-HAV IgG in high-risk persons and using pediatric formulations with a single-dose strategy have been employed to improve vaccine availability.
Several HBV vaccines are available worldwide. However, an estimated 45% of infants received a dose of HBV vaccine within 24 hours of birth among 115 countries with universal HBV birth-dose vaccination in 2022. Vaccine uptake varies by region, ranging from 18% in Africa to 80% in the Western Pacific among low- and middle-income countries. Most of the global burden of chronic HBV infection can be attributed to mother-to-child transmission of HBV peripartum or through horizontal transmission in early childhood. Scaling up HBV vaccination within 24 hours of birth is crucial. Additional HBV screening during pregnancy and subsequent tenofovir prophylaxis or universal antiviral prophylaxis when testing is not available are newer strategies to minimize transmission. Currently, there is no effective vaccine against HCV, although development of one could revolutionize HCV prevention. Implementation of adult vaccinations in settings where people with risk factors receive other services — such as refugee health centers, substance use disorder clinics, homeless organizations, HIV and STI clinics and correctional settings — will hasten vaccine coverage among adults who were not vaccinated against HBV during childhood. Preventing disease occurrence among adults will help decrease mother-to-baby vertical transmission.
Diagnostic testing and treatment targets
Expansion of access to testing and diagnostics is another vital component in the efforts to eliminate viral hepatitis. It is important for providers to routinely screen for viral hepatitis before symptoms develop and liver damage occurs. Traditional tests for HBV include detecting the presence of antigens and antibodies. HBV core-related antigen (HBcrAg) is a novel biomarker that has an important role in chronic HBV infection. HBcrAg is reported to correlate with the levels and transcriptional activities of intrahepatic covalently closed circular DNA (cccDNA), which prevents achievement of an HBV cure presently. HBcrAg could be used as a surrogate marker of cccDNA in the liver and when evaluating the efficacy of some HBV treatments. The development of a third-generation enzyme immunoassay has improved the accuracy of HCV testing with nearly 99% sensitivity and specificity. This test is not able to differentiate between acute vs. chronic infections, prompting HCV RNA quantitative testing to diagnose active infection. Viral hepatitis diagnosis remains a challenge in high-risk groups and in resource-limited areas. Barriers often encountered in these settings include limited access to health care, costs and limited laboratory resources. Point-of-care testing for both HBV and HCV have the potential to assist in overcoming these barriers by requiring only small amounts of body fluids and because they are simple to use and have shorter turnaround times to potentially achieve same-day “test and treat.”
Many countries fail to procure affordable generic viral hepatitis agents at lower prices, leading to pricing disparities. The global benchmark price of tenofovir disoproxil fumarate is $2.40 per month. Only seven out 26 countries paid prices at or below the benchmark, according to a WHO report. Similarly, a 12-week course of generic sofosbuvir/daclatasvir to cure HCV infection is available at a global benchmark price of $60 per 12-week course, yet only four out of 24 countries paid prices below the benchmark. Longer acting injectable treatments, including long-acting tenofovir, are under development. Although exciting, careful attenuation and planning about new agent costs, shipping and storage, and clinic and provider availability in areas where these are most needed will lend to overall success.
Viral hepatitis elimination requires a multipronged approach with a focus on disproportionally impacted populations. Optimization of available vaccines and effective treatments are a must while implementing creative solutions to improve diagnosis and tracking. Although the present viral hepatitis numbers may lessen optimism, elimination is within reach. Egypt once had one of the highest HCV prevalence rates in the world — roughly 10%, largely due to historic schistosomiasis control efforts, which has decreased to 0.38% over a 10-year period. A public health shift from a policy-based approach to one focused on ensuring equitable access to vaccines, diagnostics and treatment in viral hepatitis will lend to enhanced success toward elimination.
References:
- Abosheaishaa H, et al. Proc (Bayl Univ Med Cent). 2024;doi:10.1080/08998280.2024.2379185.
- HHS. Viral hepatitis national strategic plan – A roadmap to elimination for the United States 2021-2025. https://www.hhs.gov/sites/default/files/Viral-Hepatitis-National-Strategic-Plan-2021-2025.pdf Accessed Jan. 11, 2025.
- Lewis KC, et al. Public Health Rep. 2024;doi:10.1177/00333549241305256.
- Thomas DL, et al. Clin Infect Dis. 2022;doi:10.1093/cid/ciac718.
- Usuda D, et al. World J Gastroenterol. 2024;doi:10.3748/wjg.v30.i18.2402.
- WHO. Global hepatitis report 2024: action for access in low and middle-income countries. https://www.who.int/publications/i/item/9789240091672. Published April 9, 2024. Accessed Jan. 28, 2025.
- WHO. Vaccines for hepatitis A, B, and E. https://www.who.int/teams/immunization-vaccines-and-biologicals/diseases/hepatitis. Accessed Jan. 11, 2025.
- Zhang W et al. Gastroenterology Res. 2021;doi:10.1093/ajcn/nqab005.
For more information:
Jennifer Ross, PharmD, BCIDP, is an infectious diseases clinical pharmacist at M Health Fairview – University of Minnesota Medical Center. Ross can be reached at jross13@fairview.org.
Collapse
Read more about