Combating Human Viral Diseases: Lessons Learned From Hepatitis C

As the world continues to deal with the pandemic caused by the Coronavirus Sars Cov-2, it is useful to recall one of the most significant advances in the recent history of viral diseases, which is the development of pangenotypic oral direct antiviral agents for the treatment of patients of hepatitis C independent of the stage of their liver disease, with response rates of 98-100 percent. This has allowed us to cure a chronic viral disease without an effective vaccine whose development as a prophylactic measure is still under intense research. It has resulted in the establishment of new paradigms in virology, immunology and biology.

It all started with the discovery of the hepatitis C virus in 1989, identified as an RNA virus of the Flaviviridae family, composed of a 9,600-nucleotide genome-single polyprotein. The recognition of the non-structural proteins involved in its replication soon became targets of therapy, first directed to the viral NS3-NS4 protease and afterward to the replication complex NS5A and the viral polymerase NS5B, highlighting that HCV proteins exert multiple functions during the viral life cycle.

This basic research has allowed the application of new therapeutic concepts in the daily practice of clinicians. Furthermore, it has had a positive, amazing impact on the daily life of patients. The road to that purpose was achieved by the practice of multiple clinical trials worldwide that demonstrated the efficacy and safety of the oral direct antiviral drugs with very few side-effects

On Oct. 5, 2020, the Nobel Prize in physiology or medicine was awarded jointly to Harvey J. Alter, Michel Houghton and Charles M Rice for the discovery of the hepatitis C virus. They made seminal discoveries that led to the identification of this novel virus and made possible blood tests and new medicines that have saved millions of lives. Globally, approximately 71 million people and 600,000 in Mexico, have chronic hepatitis C. Most of them are, however, still unrecognized because the infection is habitually silent until 20-30 years later when chronic liver disease ensues.

The impact of hepatitis advances is best exemplified by the fact that WHO launched a call to eliminate hepatitis C by 2030, establishing global guidance for countries for that purpose, recognizing that the epidemiology and progress toward hepatitis C elimination varies by country. In Mexico, for example, the average age at diagnosis of hepatitis C is 60.7 years and 44 percent have liver cirrhosis, indicating that patients are arriving late to diagnosis and treatment.

Screening for HCV infection is central for identifying unknown cases. The early diagnosis of HCV infection can help to reduce the burden of disease and limit transmission to those at risk of infection or reinfection. Screening is, therefore, critical to achieving the WHO targets by 2030.

Unfortunately, a high percentage of HCV-infected people live in countries with limited resources to screen and treat hepatitis C. There is still a need to overcome numerous challenges, such as lack of awareness among health professionals and the public in general. Each country needs to plan its public health policy and screening strategy but overall linkage to care remains an important hurdle.

A lack of knowledge regarding risk factors and treatment may contribute to low cure rates. Risk factors for hepatitis C have changed over the years.  While blood bank screening has become almost universal, prevention and control of HCV should focus on recognizing other high-risk populations, such as users of intravenous or intranasal drugs, people deprived of their liberty, patients with chronic renal failure in pre-dialysis, those in hemodialysis or co-infected individuals with HIV/hepatitis B. The evolution of these risk factors will provide insights into understanding the future burden of hepatitis C.

Mexico has now implemented a multidisciplinary national program toward the elimination of hepatitis C under the guidance of the National Council of the Prevention and Control of HIV/AIDS (CONASIDA), considering its experience and success in reducing and stabilizing the HIV epidemic through diagnostic and monitoring strategies in key and risk populations. The program will provide free access in the public sector to diagnostic testing, including viremic confirmation by PCR techniques and free access to oral direct antiviral agents. An observation center has been implemented to obtain epidemiological information at the national level to determine and quantify the prevalence, incidence and comorbidity associated with HCV infection; identify training needs for health personnel; reach people with risk factors for infection; and offer follow-up and reporting to a system centered on persons and communities. Harm reduction programs are being installed, community leaders are being identified to facilitate equity in the program and a strategy to foster hepatitis C awareness is being advanced.

Robust basic and clinical research into viral infections, such as that which has taken place regarding hepatitis C, will prove to be very significant in the control of future viral pandemics.