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The Global Elimination of HCV

In May 2016, the World Health Organization (WHO) issued its first global strategy for the elimination of viral hepatitis, including the elimination of Hepatitis C virus (HCV) as a public health concern, by the year 2030.

According to the WHO, this means a

• 90% reduction in the transmission of the virus, and a
• 60% reduction in HCV-related mortality.

The continued increase in morbidity and mortality due to HCV infection necessitates this elimination strategy: there were an estimated 1.7 million new cases of HCV globally in 2015, and the disease burden is likely much higher than the epidemiology data reflect. The millions of new cases of HCV impact not only mortality but also the quality of life of those who become infected; this huge disease burden, in turn, creates financial burdens for individual patients and health care systems.

With the advent of safe, tolerable, and highly effective direct-acting antiviral (DAA) medications, sustained virologic response (SVR) is attainable in greater than 95% of those treated. With no effective vaccine against HCV currently available, DAAs will form the foundation of HCV elimination.

Treatment, though, is only one component of an effort that must also focus on prevention, screening and diagnosis.

Barriers to elimination

Blood and injection safety are a very important part of HCV prevention. Countries must establish national viral hepatitis plans to reduce the spread of transmission through transfusions, sharps injuries, inadequate sterilization, and the reuse of injection equipment. While the risk of acquiring HCV infection via blood transfusion is much lower in the U.S. and other high-income countries — about 1 per 2 to 3 million transfused units — in many low- to middle-income (LMIC) countries, especially in Africa, that risk is still very high, at 2.5 per 1,000 transfused units.⁴ The transmission of HCV (and other blood-borne pathogens) can be greatly reduced through the screening of donor blood; currently, however, only 28% of LMIC countries use donor blood screening systems. Proper training in the safe use and disposal of sharps is also vital to preventing accidental transmission via needle stick.

Increasing prevalence of HCV among injection drug users

While unsafe healthcare practices (including unscreened blood products and the reuse of injection and medical equipment) are the most common modes of HCV transmission worldwide, there is an increasing prevalence and incidence of HCV infection among injection drug users. Injection drug users are a group that includes former and current injectors, even those who have injected just once during their lifetime.

• There is a 50% prevalence of chronic HCV infection among injection drug users, and the group comprises 8% of all HCV infections worldwide;
• 23% of the 1.7 million new HCV infections reported in 2015 were attributed to injection drug use.

Needle-sharing programs and opioid substitution therapy have shown to be effective in reducing transmission in this population. Combined, the two programs can reduce the incidence of HCV by up to 80%. Unfortunately, as of 2016:

• Only 57% of countries with reported injection drug use have needle-sharing programs;
• Only 51% of countries have opioid substitution therapy, even though both methadone and buprenorphine are on the WHO list of essential medicines; and
• The areas with the lowest number of needle-sharing programs and opioid substitution therapy are Latin America, the Middle East, and Africa; though even in the U.S., coverage of opioid substitution therapy is hindered by the use of alternative opioid substitutes with questionable efficacy.

Many injection drug users are unaware of their HCV status, resulting in the continued transmission of HCV in this population. It remains that many people with active HCV infection are asymptomatic for years following the initial infection, and those people will not seek treatment. Injection drug users who are experiencing symptoms or who suspect they may be infected are often disinclined to seek health care due to a number of factors, including prior negative experiences and a fear of stigma or judgement.

There is often a lack of access to health services, as well, including a shortage of health care practitioners, limited hours of service, and long wait times, all of which may discourage people from seeking care. The two-step diagnostic process continues to be a barrier, as many individuals with positive antibody screening tests are lost to follow-up and never receive HCV RNA testing for confirmation of active infection.

And, of course, there are barriers to treatment, as well. While the efficacy of DAAs makes them cost effective in the long term, the up-front cost of these drugs often drives treatment decisions.

• The WHO added daclatasvir, sofosbuvir, ledipasvir, simeprevir, and ombitasvir/paritaprevir plus dasabuvir to its list of essential medicines in 2015, but all these medications will remain on patent until at least 2029, placing them beyond the financial means of many patients, especially those who are most in need of treatment.
• In many countries, the use of these drugs has been reserved only for the sickest patients, negating the cost-effectiveness of the drugs altogether, as treatment delay leads to an increased risk of cirrhosis, hepatocellular carcinoma (HCC), and death. Importantly, it also creates a much larger window of time during which infected patients can continue to spread the disease.

Addressing the challenges: Screening

First and foremost, risk-based screening programs are needed both to prevent transmission and to identify infected individuals as early as possible to avoid long-term complications. Several options can simplify the process and reduce the cost of testing, making HCV screening more accessible to underserved populations.

• HCV core antigen testing is much less expensive than HCV RNA testing and is run as a fully-automated assay, with similar sensitivity and specificity to the RNA test. Core antigen testing can also be performed on dried blood spot (DBS) samples; while this is slightly less sensitive than serum, it is a good option for marginalized populations with limited facilities, as DBS samples do not require any refrigeration or special storage procedures.
• Reflex testing is another option that can be used to minimize loss to follow-up. Blood is drawn for both the antibody screening test and the HCV RNA test during the patient’s visit; if the antibody test is positive, the HCV RNA test is automatically ordered. This eliminates the need for the patient to return for a second blood draw.
• In LMIC areas, it may be worthwhile to incorporate HCV screening and care into existing HIV and TB care services, making HCV diagnosis and treatment more accessible to those in otherwise difficult-to-reach areas.

Addressing the challenges: Care integration

If HCV care services are integrated into addiction care services, this may foster a positive environment where patients feel comfortable with staff and don’t fear discrimination from providers. Injection drug users are a population that faces unique challenges, and a blanket approach to diagnosing and treating injection drug users is not feasible. To reach as many people as possible, HCV care should be provided not only in hospitals and addiction centers, but also through primary care and mid-level providers – and these health care providers must be educated about HCV.

The expansion of needle and syringe exchange programs and opioid substitution therapy services is also vital to reaching the WHO elimination goal.

While elimination of HCV isn’t possible without increased prevention and diagnostic measures, it remains that DAAs are the backbone of the elimination effort.

• Achievement of SVR reduces the risk of liver fibrosis, decompensation, and HCC – and reduces the risk of death by up to 84%.
• Moreover, in the DAA era, treatment is medically available to many more patients. Guidelines from the American Association for the Study of Liver Diseases (AASLD) state that all patients are eligible for treatment with DAAs, aside from patients for whom life expectancy is not likely to be corrected by treatment or liver transplant. This has resulted in a treatment rate of 77%, compared to 22.3% in the IFN era.

In the U.S., the average cost of a 12-week course of DAA treatment is $70,000.⁴ These drugs must be made more affordable, and public and private health care plans need to make DAA treatment available to all HCV patients, removing the restrictions that allow only the sickest to be treated. A committee composed of representatives from the CDC, HHS, AASLD, the Infectious Disease Society of America, the National Viral Hepatitis Roundtable and the National Academies of Sciences, Engineering, and Medicine has recommended the creation of a voluntary transaction between governments and pharmaceutical companies that would allow the companies to compete for the licensing of a patented drug that the government would then use to treat underserved populations with HCV. This has been successful in several LMIC countries, including Egypt, which has the highest prevalence of HCV in the world.

Egypt, for their part, has created a plan to treat 5 million patients by 2030. By significantly reducing treatment cost and implementing a universal test-and-treat program that allows some patients to begin treatment as soon as one week after diagnosis, they have been able to treat hundreds of thousands of patients already.

The prospect of global elimination of a disease that affects 150 million people is formidable: the scope, cost, and complexity are intimidating. However, we have all the tools needed to make the goal a reality. A global strategy has been created, reliable diagnostic tests are available, and safe and highly effective medications exist. The successful implementation of these tools will result in the saving of billions of dollars spent treating the complications of a curable disease, and, more importantly, it will result in the saving of tens of thousands of lives.

References

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