July 13, 2023
By Benedetta Pelosi, MS, Patricia Perkins, MSPH, William M. Remak, MPH, MS, MT, Zahra Seid MD, MPH, DrPH, and Maia Romanowska
The 2022 World Health Organization (WHO) reportopens in a new tab or window estimated 58 million people live with chronic hepatitis C, while approximately 40% of people are unawareopens in a new tab or window of their infection. The hepatitis C virus (HCV) genome, discovered in 1989, is a spherical, enveloped, positive-strand RNA virus, and has many genotypes according to Simmonds genotyping systemopens in a new tab or window. A highly anticipated hepatitis C vaccine is currently under development and review in clinical trials. If deemed safe and effective, this will be an essential tool for eradicating hepatitis C and relieving its heavy disease burden.
Why Is Hepatitis C a Major Liver Disease Concern?
Globally, infectious diseases are major causes of human suffering, and blood plays a significant role in transmitting infectious diseases such as HCV, human immunodeficiency virus (HIV), hepatitis B virus (HBV), malaria, and others. Malaria and hepatitis C virus infections are common causesopens in a new tab or window of human suffering with overlapping impact. Hepatitis C causes both acute as well as chronic liver disease in 60%-80%opens in a new tab or window of the cases, and chronicity is reported to be associated with the development of cirrhosis (15%-30%) and liver cancer. Liver damage caused by HCV is one of the most frequent indications for liver transplantation worldwide.
In 2022, the WHO approved the Global Strategyopens in a new tab or window to eliminate hepatitis C infection by 2030. To achieve this goal, the WHO plans to attain a 90% reduction in new cases of chronic hepatitis C, a 65% reduction in HCV deaths, and treatment of 80% of eligible people with chronic hepatitis C infections. Since 2015, the number of people who received treatment for HCV increased nine-fold globally, to 9.4 million. Hepatitis C eradication can be achieved only by developing holistic, integrated solutions for the prevention and treatment of viral hepatitis.
The Challenges and Solutions to Achieve Eradication
Screening, treatment, and linkage to care for at-risk populations have made progressopens in a new tab or window, yet in most countries, many people living with chronic HCV have not been tested or treated since acute HCV usually goes undiagnosed (as it rarely causes symptoms). Developing appropriate and cost-effective screening and testingopens in a new tab or window algorithms are essential, but these may not lower the potential cost of care downstream compared to initial prevention of HCV by vaccine.
The acquisition costs of direct-acting antivirals (DAAs) can impose limitations in accessopens in a new tab or window for patients and influence the costs of healthcare resource utilization. In response, the Clinton Health Access Initiative and The Hepatitis Fund recently announcedopens in a new tab or window two new Memoranda of Understanding to dramatically lower the price of WHO prequalified hepatitis B and C drugs in low-and middle-income countries.
HBV/HCV co-infection is a more severe liver disease and an increased risk for liver cancer. Co-infection with HBV and HCVopens in a new tab or window is common because of their common route of transmission, especially in regions of the world where both viruses are endemic. HBV reactivation has been observed in people with HBV infection during HCV treatment with direct-acting antiviralsopens in a new tab or window. The development of an effective prophylactic or therapeutic vaccine is therefore necessary to achieve global epidemic control of this virus and long-term elimination. Successful use of the hepatitis B vaccine, as a model, demonstrates what can be accomplished when an efficient vaccine becomes approved and deployed.
Another challenge is the lack of reliable data post-pandemic. The existing WHO regional models do not capture the significant heterogeneity between countries within the same region, including differences in epidemic characteristics, prevention, population groups, costs, existing health systems, and particularly the differences between high-income and low-income countries. In all the epidemiological HCV studies, countries reporting with missing data are excluded from regional averages, biasing projections towards the epidemiological situations of countries with better surveillance and reporting systems. The recent 2022 CDC surveillance reportopens in a new tab or window should be interpreted cautiouslyopens in a new tab or window since there is a lack of accurate and timely data for fully understanding the disease burden. More researchopens in a new tab or window is needed to examine trends in geographic areas and communities with variable access to resources.
The Need to Prioritize HCV Vaccines and DAA Cures
“An ounce of prevention is worth a pound of cure,” Benjamin Franklin would say in this case. A vaccine for HCV, as a prevention measure, is necessary for disease eradication. HCV is frequently undiagnosed, leading to challenges in surveillance and mass screening programs, further aggravated by the loss of health workers due to the pandemic.
Vaccinations are proven to be important preventive measures that improve wellness and allow individuals to contribute to economic growth. In low-income countries, infectious diseases still account for a major proportion of deaths, highlighting health inequities caused by economic differences. Immunizationopens in a new tab or window has prevented deaths in all age groups from diseases like diphtheria, tetanus, pertussis, influenza, and measles, confirming they are the most successful and cost-effective public health interventions able to reduce inequities. Areas with high immunization discourage circulation of pathogens, thus decreasing the likelihood of outbreaks.
For the HCV vaccine, we can learn from the similarities between SARS-CoV-2 and HCV. SARS-CoV-2 and HCV have both shown a considerable amount of genetic diversityopens in a new tab or window for evading the host immune response. Single stranded RNA virusesopens in a new tab or window are notorious for their ability to mutate faster than DNA virus, and their high genetic diversity complicates the development of broad-spectrum vaccine protectionopens in a new tab or window. Examining prior vaccine development, that of SARS-CoV-2 for example, can offer insights in understanding and monitoring the complex ability of viruses to generate successful escape mutations due to various pressures.
Summarizing the Future
In conclusion, development of a safe and effective HCV vaccineopens in a new tab or window could be highly preventative and target complex envelope proteinsopens in a new tab or window of a pathogen that exhibits a high rate of escape mutations. Vaccines are key players for eradicating and addressing variants of viruses including HCV. The rapid and effective development of vaccines against SARS-CoV-2 highlights what may be possible for HCV: if HCV scientific endeavors are highly supported and coordinated, we may have a chance to tackle the disease’s major health burden.
Benedetta Pelosi, MS, Patricia Perkins, MSPH, William M. Remak, MPH, MS, MT, Zahra Seid MD, MPH, DrPH, and Maia Romanowska are all members of the Global Immunization Action Network Teamopens in a new tab or window (GIANT) of the California Hepatitis C Task Force.
Read More at Medpage Today.