Hepatitis C: Eliminating an Epidemic

Is it possible for the world to coordinate its efforts to destroy the threat of a virus that annually affects over a million people per year? The World Health Organization (WHO) thinks so. Better yet, it believes we can do so as early as 2030 [1]. Hepatitis C is a liver infection caused by the hepatitis C virus (HCV) which, in half of those infected, can progress to a long-term, chronic infection if left untreated. YetHowever, only 40% of those living with hepatitis C actually know they are infected [2]. WHO states that the elimination of hepatitis C as a global threat entails the diagnosis of 90% of all HCV-infected individuals and 80% of those to be treated. Staggeringly high rates of global HCV infection and low treatment uptake have raised doubts in the feasibility of WHO’s goals. Furthermore, there has yet to be a general systemic approach to HCV screening and testing employed on a global scale. There is evidently much work to be done to achieve hepatitis C elimination by 2030, but any hope of meeting this goal must begin with the adoption of an internationally-coordinated diagnostic test-and-treat plan that is robust and accessible.

While much can be done to improve hepatitis C screening, the treatment aspect of the battle against hepatitis C is undoubtedly excelling. Beginning with their introduction to the general public in 2013 with the approval of sofosbuvir, direct-acting antivirals (DAAs) have been used as a first-line treatment for HCV infection. Taken orally over an 8-week course, 90% of those treated with DAAs are cured of their HCV infection. Even though a standard course of DAA treatment in the US can cost up to $27,000, undergoing DAA treatment significantly reduces the costs of managing complications in severe stages [3]. Hence, DAA treatment is a cost-effective method of treating those living with hepatitis C. Despite the expanded availability of DAAs at cost-effective prices, only 20% of HCV-infected individuals are treated [4]. Such a surprisingly low treatment rate can be attributed to global differences in HCV treatment uptake. Certain nations are well on their way to meeting the benchmarks set by the WHO for hepatitis C elimination simply due to higher HCV treatment uptake. Conversely, nations with sparse access to treatment options and an inefficient diagnostic platform have naturally grown their respective hepatitis C patient pools and epidemic rates. Adopting a singular, globally-accessible, one-step, test-and-treat diagnostic approach is therefore a necessary step to identify undiagnosed HCV positive individuals and provide easy access to DAA therapy which has hitherto been proven to be a powerful, cost-effective treatment.

Identifying a one-step, point-of-care, test-and-treat screening system will simplify the overall hepatitis C care process and accelerate progression towards WHO’s benchmarks. A perfect diagnostic system for HCV infected individuals would involve providing a simple blood or oral fluid sample, receiving a diagnosis of an active HCV infection, and starting treatment immediately all at the same location on the same day. Thus, this “test-and-treat” model enables HCV-infected individuals to have access to early treatment and diminishes the rate of spread of HCV. Patients would then return to the same location to confirm their cure of HCV infection upon the completion of their treatment course. Such a model would link those with active HCV infection to immediate care and thereby drastically escalate the likelihood of those infected receiving treatment [5]. Unfortunately, no system of this sort has been established in such a way that could be applied on a global scale [6]. All hope is not lost, though. Current point-of-care platforms can be adjusted to serve as a viable option. Reverse-transcription loop-mediated isothermal amplification assays (RT-LAMP) are fast, sensitive, and an ideal one-step centerpiece to a test-and-treat diagnostic model. RT-LAMP is highly advantageous when aiming to reduce total wait time, acquire easily-readable results, and minimize overall platform complexity. HCV’s genome is a single stranded RNA molecule. Thus, if current RT-LAMP technology were modified, it could be used to identify the presence of HCV RNA in a sample to diagnose for active infection [7]. The development of such an assay has yet to be developed, but nonetheless is a worthwhile future direction that can ensure that active HCV infection diagnoses can be received quickly so that treatment can begin the same day. Therefore, the 80% of individuals who are not treated after a hepatitis C diagnosis should be more inclined to receive treatment if their diagnosis was received quickly, and the health center at which the diagnosis was given can then immediately begin treating the patient.

Given its current trajectory, the elimination of hepatitis C seems to be a noble yet far-fetched concept. Too few people are currently receiving treatment upon a positive diagnosis, and far too many undiagnosed HCV-positive individuals remain. In fact, the HCV diagnostic rate in the US hovers around only 50%. In Europe, that number drops to around 36%. If WHO’s 2030 benchmark statistics are to be met, a centralized, one-step diagnostic platform that combines a quick diagnostic turnaround time with easy linkage to DAA treatment must be adopted in global synchrony. Should we give up hope that hepatitis C can ever be put an end? Not yet. Much work is to be done, but with changes to the current hepatitis C care platform, hepatitis C can be defeated.

References

1. Dore, G. J., & Bajis, S. (2020). Hepatitis C virus elimination: Laying the foundation for achieving 2030 targets. Nature Reviews Gastroenterology & Hepatology, 18(2), 91–92. https://doi.org/10.1038/s41575-020-00392-3

2. Hepatitis C - FAQs, Statistics, Data, & Guidelines. Centers for Disease Control and Prevention. Retrieved from https://www.cdc.gov/hepatitis/hcv/index.htm#:~:text=Hepatitis%20C%20is%20a%20liver,to%20prepare%20and%20inject%20drugs.

3. Dhiman, R. K., & Premkumar, M. (2020). Hepatitis C virus elimination by 2030: Conquering Mount Improbable. Clinical Liver Disease, 16(6), 254–261. https://doi.org/10.1002/cld.978

4. Shahid, I., Alzahrani, A. R., Al-Ghamdi, S. S., Alanazi, I. M., Rehman, S., & Hassan, S. (2021). Hepatitis C diagnosis: Simplified Solutions, predictive barriers, and future promises. Diagnostics, 11(7), 1253. https://doi.org/10.3390/diagnostics11071253

5. Applegate, T. L., Fajardo, E., & Sacks, J. A. (2018). Hepatitis C virus diagnosis and the holy grail. Infectious Disease Clinics of North America, 32(2), 425–445. https://doi.org/10.1016/j.idc.2018.02.010

6. Sussman, N. L., Remien, C. H., & Kanwal, F. (2014). The end of Hepatitis C. Clinical Gastroenterology and Hepatology, 12(4), 533–536. https://doi.org/10.1016/j.cgh.2014.01.025

7. Jiang, M., Pan, W., Arasthfer, A., Fang, W., Ling, L., Fang, H., Daneshnia, F., Yu, J., Liao, W., Pei, H., Li, X., & Lass-Flörl, C. (2020). Development and validation of a rapid, single-step reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) system potentially to be used for reliable and high-throughput screening of covid-19. Frontiers in Cellular and Infection Microbiology, 10. https://doi.org/10.3389/fcimb.2020.00331