What We Need to Eliminate HCV in the U.S. —Alan Franciscus, Executive Director
The multimedia review journal Clinical Liver Disease published a series of articles that provided important information about the tools needed to eliminate hepatitis C (HCV). This report is a review of the articles and is specific to the United States. It doesn’t address the political issues that are equally, if not more, important.
Medicaid Treatment1– State Medicaid programs are required by law to cover HCV direct-acting antiviral (DAA) therapy without restriction, but many states still limit coverage of these medications. These restrictions on DAA treatment are based on disease severity, sobriety (drug and alcohol) and the medical specialty providing treatment. These restrictions are not based on scientific evidence and lead to poorer treatment outcomes, higher future medical costs, and more importantly, they put patients at risk for worse health problems now and in the future. All patients should receive DAA therapy including those people who are eligible for Medicaid. To read more about HCV and Medicaid coverage to go: http://nvhr.org/hepatitis-c-state-medicaid-access
Hepatitis C Vaccine Development2 – One of the most vexing problems in HCV has been the lack of the development of a protective vaccine against HCV. An effective vaccine to protect against HCV is one of the most important strategies to eliminate HCV. A vaccine will protect populations at highest risk of acute infection including people who inject drugs, healthcare workers exposed to blood or bodily fluids, people who receive hemodialysis (filters blood when the kidneys are no longer working) and other people who are at risk for HCV infection.
The high mutation rate of the various parts of the hepatitis C virus is one of the biggest obstacles to developing a protective vaccine. There is a hint of a vaccine in the form of evidence of natural immunity in some people. Natural immunity against HCV is also found in laboratory studies in animal models, but scientists have not been able to replicate this process into an effective vaccine. Although there has been some progress, an effective vaccine remains elusive.
In the review article, the authors discuss various vaccine approaches. Due to the mutation process discussed above, researchers have had to develop models outside of the usual antibody specific type models used in other vaccines. Instead, other parts of the hepatitis C viral proteins are under study. One approach is to induce T cell-mediated immunity that causes CD8+ T cells (white blood cells that kill infectious cells) that are specific to HCV to clear the virus from the body.
Still, other researchers are focusing on non-infectious HCV-viral like particles to induce an antibody response.
Currently, there are many vaccines in pre-clinical, phase 1 and phase 2 clinical studies. For more information and to enroll in vaccine studies, go to www.clinicaltrials.gov Type in HCV Vaccine.
Diagnostic Tools3 – In their review, the authors discuss the importance of developing effective diagnostic tools that can take a patient from the initial diagnosis of HCV (antibody test), confirmatory HCV RNA (viral load) to starting DAA therapy. Initially, the HCV test will decide if the infection is acute or chronic. Acute is the rapid onset of a recent infection that can be determined by risk factor assessment and various blood tests including an HCV antibody test. A positive HCV viral load after six months means that someone has chronic HCV.
If the person has a positive HCV viral load test, they can start the process of medical management (insurance, medical providers, medical tests, treatment and hopefully cure).
The problem with our medical system is that there is a large failure in tracking and care of patients from initial HCV antibody positive testing to starting DAA treatment and cure. The authors use an example of patient’s lost to follow-up:
- 715 (100%) patients had a positive HCV antibody positive test,
- 488 (68%) patients were tested HCV RNA (viral load),
- 388 (80%) tested were positive for HCV RNA,
- 223 (57%) started treatment,
- 201 (90%) completed treated and,
- 180 (46%) achieved a cure—a 90% cure rate.
In this analysis, out of 715 patients originally tested for HCV, only 223 started treatment.
The article discusses various HCV diagnostics tools (listed below). All of the patients need follow-up contact for the HCV viral load results and further action. However, initial testing can provide an opportunity for counseling and further medical care.
Reflex Testing: this process uses the leftover blood sample (tube) from an HCV antibody result to test for HCV viral load test. An important point to make is that the blood tubes need to be stored between the tests to prevent the blood samples from degrading. The costs are higher with this type of testing. Reflex testing would eliminate the need for a person to come back for another blood draw. A patient would have to be contacted for the results and follow-up medical care if the HCV viral load results are positive.
Dried Blood Spot Testing (DBS): A finger-prick whole blood sample is is applied to a DBS card. It can be a single blot or applied in multiple blots on the same card. The DBS card can be returned via USPS mail or shipped with another carrier. The blood spots can be used to test for HCV antibody and HCV viral load. The HCV viral load has to be greater than 4 log IU/mL which is the vast majority of viral loads of people with HCV. Another advantage of DBS is that it can also test for HIV, hepatitis B (HBV) and syphilis. In addition to testing for other diseases, the DBS test would eliminate the need for further testing, and a patient could be contacted to start the process of seeking medical care.
Point-of-Care and Rapid Diagnostic Tests: The Oraquick finger-prick and oral swab tests allow for HCV antibody results in 20 minutes. If the HCV antibody is positive, a follow-up HCV viral load test would be necessary to confirm the diagnosis.
There is also a rapid HCV viral load test that uses a drop of whole blood to give results in 90 to 100 minutes. The rapid HCV viral load test is not approved in the United States. Outside of the United States, some countries use it to confirm chronic HCV.
Challenges: The authors point out that in every HCV diagnostic test there are limits based on the HCV population, and how to move them through the treatment continuum. For instance, in people who inject drugs, the DBS may be more useful than drawing a blood sample due to issues related to finding a vein to draw blood for a reflex test. People who are in prison need to have trained staff and linkage to care when released from prison. Non-native English speakers need translators for testing and linkage to care. The bottom line is that there is no one size fits all testing procedure.
Acute HCV4 – In the absence of a protective vaccine, an approach is needed to treat people newly infected with hepatitis C. Risk-factor assessment and various diagnostic tests can identify newly acquired HCV infection. In acute infection, 20% to 50% of people spontaneously clear the virus –that is their body will naturally clear the virus. If HCV RNA (viral load) is present after 6 months, the infection is chronic, and treatment with DAA therapy can be started. In most studies of DAA therapy, the treatment period of 8 weeks has produced cure rates approaching 100%. Other studies have found shorter treatment periods have produced similar cure rates.
HCV Populations5 – In the past, certain populations infected with HCV have had sub-optimal cure rates with interferon-based therapies. Now that DAA-based therapy is available that is no longer the case:
- African Americans: near 95%
- HIV/HCV coinfection: up to 98% cure rates
- Renal (kidney) impairment: up to 98% cure rates
- Decompensate cirrhosis: up to 94% cure rates
People Who Inject Drugs (PWID): PWID comprise the main population who are at risk of acquiring HCV. The current rates of newly acquired infections are up to 70%. Treatment of PWIDs has produced up to 97% cure rates. The reinfection rates have been low. PWIDs are the group acutely infected with HCV; we must engage, treat and cure PWID to eliminate HCV.
Children 12 years of age and older: Treatment with DAA therapy is approved to treat children 12 years of age and older. The cure rate are 98% to 100%.
Unanswered Treatment Questions:
HCV in Pregnancy: Every year 29,000 pregnant women and 1,700 infants in the United States are estimated to be infected with HCV. Mother-to-child transmission occurs in
5.8% of mono-infected women and up to 10.8% of HIV/HCV coinfected women. The American Association for the Study of Liver Disease (AASLD) recommends a one-time HCV test for all pregnant women. However, Kentucky is the only state that requires by law that pregnant women are tested for HCV.
Currently, there is no guidance for the use of DAA therapy to treat pregnant women with HCV to prevent transmission of HCV from mother-to-child, and no drugs are approved to treat infants for HCV.
Children 12 years of Age and Under: The current recommendation is to wait until children are 12 years of age to treat or until more evidence is available to understand if DAA treatment is safe.
The article did not address the most important part to eliminate HCV—that is the political will to provide the resources on a local, state and national level. There is some movement towards the elimination of HCV in some countries. Some U.S. states have committed to eliminating HCV, but the U.S. Government has not committed—yet!
Clinical Liver Disease – Free Access
Volume 12, Issue 5 Pages: 117-149 – November 2018 https://aasldpubs.onlinelibrary.wiley.com/toc/20462484/2018/12/5
1Rationing Care: Barriers to Direct-Acting Antiviral Treatment in Medicaid Treatment Criteria– Phil Waters J.D., Tina Broder M.S.W., M.P.H.,
2Hepatitis C Vaccine Development in the Era of Direct-Acting Antivirals – Matthew McConnell M.D., Joseph K. Lim M. D.
3Hepatitis C Virus Diagnostics: The Road to Simplification – Jordan J. Feld M.D., M.P.H.
4Hepatitis C Virus Standard of Care: A Rapid Evolution and Considerations for Acute Hepatitis C Virus – Tram T. Tran M.D.
5PRO: Patients With Hepatitis C Virus With Pretreatment Metavir Stage 3 Fibrosis Do Not Require Hepatocellular Carcinoma Surveillance After Sustained Virological Response – Amoah Yeboah-Korang M.D., M.P.H., Nicole M. Gentile M.D., Claus J. Fimmel M.D.Share This Page