The history of the hepatitis C virus (HCV) is a strong example of a bench-to-bedside approach illustrating how basic scientific knowledge is applied to patient care.

Following the discovery of hepatitis B virus (HBV) in 1965[1], and hepatitis A virus (HAV) in 1973[2], a clinical entity known as post-transfusion non-A non-B (NANB) hepatitis became more evident[3]. This was regardless of the banning of commercial blood donations systems, and the implementation of HAV and HBV blood testing in 1975[3,4]. Furthermore in 1989, after years of intensive research[5], a scientific breakthrough discovered another virus consisting of a single positive strand of RNA, the HCV, classified in the Flaviridae family[6]. HCV was determined to be the causing agent of the post-transfusion NANB hepatitis[4,5].

In 1992, following the cloning of HCV, an evolving series of sensitive and specific anti-HCV antibody immunoassays were developed which allowed for the mandatory testing of blood collections in the United States[3]. Subsequently, third-generation immunoassays and RNA-HCV nucleic acid amplification tests improved the diagnostics of HCV for blood transfusion safety[7]. During the 90’s, the HCV genotypes and subtypes, as well as their heterogeneous geographic distribution became apparent through basic research and molecular epidemiology[8]. Additionally in the United States, blood transfusions, injection drug use (IDU) and several medical procedures were identified as high-risk factors[3].

During the 90’s but before 2011, the first antivirals to be marketed were standard interferon, followed by pegylated-interferon which was later combined with ribavirin[9]. Unfortunately, these antivirals achieved a low-level of sustained viral response (SVR) among patients with HCV genotype 1 compared to other genotypes[10]. However after 2011, the first and second generation direct-acting antivirals based on targeting the specific molecules of the HCV life cycle have proven more efficient regardless of genotype reaching an SVR in more than 90% or 95% of the patients who receive treatment[10].

In recent years, DNA sequencing and bioinformatics of HCV strains worldwide have allowed the evolutionary analysis and molecular tracing of the HCV epidemic across countries, mainly focusing on genotype 1a and 1b[11]. These studies have documented the prevalence of HCV in Japan since 1920, in Europe since 1940 and the United States since 1960[11,12]. Further studies have confirmed that the introduction of HCV in the United States may have occurred even earlier (in the 1950’s) and is related to the use of contaminated blood obtained from commercial blood donors and the return of World War II soldiers[13]. These reasons, along with the fact that hepatitis C is a stealthy virus causing injury to the liver in a silent manner, people who were born from 1945-1965 are currently in the target population of the “baby boomers” screening campaign for HCV in the United States[14].

Mexico’s geographic location serves as a common pathway of intracontinental migration between the United States and other countries of LA. Thus, HCV could have spread from the United States to this region. However in LA, awareness of an NANB hepatitis did not intensify until the late 1970s and early 1980s[15]. During this period, the United States veterans returning from Vietnam, as well as the migration of Latin Americans to their homeland as retirees or by multiple processes of deportation and migration between countries became a major social-demographic phenomenon.

The first HCV epidemic outbreak was associated with the emergence of HIV in the mid-1980s, at a time where the presence of paid blood donors was a common situation[16]. This parenteral route of transmission may have been the primary source of dispersion in Central and South America since IDU, during those decades, was very rare in LA[17]. Furthermore, even though in the United States mandatory screening of blood-borne viruses had been implemented in 1992, it was not fully established in Mexico and LA until 1996[18,19]. This information indicates that even before 2000, blood donations contaminated with HCV were still a relevant risk factor[20]. Moreover, an additional route of HCV infection in the LA may have been the indiscriminate use of caesarean births and other medical procedures that took place during the same period[21]. Brazil and Mexico[22] are the two countries with the highest rates of cesarean sections within the Americas[23]. This could explain why Mexico has a female-to-male ratio of 2:1 of HCV infection[21].

Although partial reports were stating the frequency of HCV in countries of LA during the 1990s, it was not until after 2000 that HCV-related liver cirrhosis began to rise. In Mexico, this disease entity represents over 12 deaths per 100000 inhabitants and the estimated number of people infected with HCV may range from 1.5 to 2 million[24-26], and at least ten million in LA[26-28]. In this region the route of transmission of HCV may have been similar as it was in Mexico, taking into account that as of 2000 the use of IDU, as well as tattooing and piercing, had increased from that year forward[17].

The health officials have not considered viral hepatitis to be a severe health problem, which in turn has manifested ignorance or reluctance towards a state program of detection or treatment of this disease. Consequently, there are a limited number of up-to-date population-based epidemiological studies of viral hepatitis in most LA countries[35,36] sponsored by the government. The few that do exist are accomplished by the attention and personal interest of researchers, rather than the concern of the health authorities. This lack of concern from the health authorities translates into key factors and information being overlooked. Some of these factors include; lack of precision of who and how many people are infected, primary risk factors involved[50], transition in genotypes[17] and co-morbidities (obesity, diabetes, alcoholism, co-infection with HVB and HIV)[51]. Furthermore, these epidemiological studies need to be documented in the population of LA because most clinicians assume that the same SVR achieved in Caucasians will replicate in people from this region.

In LA, including Mexico, most medical societies involved in the study of the liver have a limited number of members with a solid scientific career, based on their poor scientific productivity in indexed and high impact factor journals in their dedicated fields[52,53]. These society members are hosted by the pharmaceutical companies to attend international forums. In turn, they are the only speakers that echo their experience at the liver meetings to their fellows but do not contribute with scientific data or share their clinical experience. This circumstance has led to the situation that some members only intend to be their society’s President (or Chairperson) without the actual contribution of new knowledge in their field of expertise. Moreover, it is precisely these “leaders of the field” who take part, on multiple occasions, as representatives of the health authority, sometimes playing a dual role as clinician and politician.

Therefore, when the support of the medical community is required to establish health policies that have an impact on vulnerable social groups, the members are left without a voice, and vote, on these issues. Consequently, the decisions are made in an unipersonal manner. Furthermore, if the clinician-politician now has a position within the health institutions or the government, he/she may now have a conflict of interest with his/her private practice.

Unfortunately, the lack of an official standpoint in many educational or health institutions to promote a high standard of scientific and academic quality is a serious weakness. This challenge, paired together with a high level of corruption and preferential treatment that prevails among some government authorities, makes it tough to provide treatment for this virus. This situation has created elitist groups of treating physicians being sponsored by the pharmaceutical industry. These doctors may be knowledgeable, however, in some cases, this information does not necessarily apply to their respective countries or communities.

Furthermore, many of these physicians focus on his/her private practice and have negligible interest in understanding the reality of the disease in their community or country of origin. A reminder of the Hippocratic Oath is “We as doctors should seek the best benefit for the patients, including those who do not have access to treatment“.

Likewise, in the majority of LA countries, there are no specialists in hepatology. Patients living with liver diseases are treated mainly by a gastroenterologist or internist[54]. However, with the introduction of the new effective antivirals, and the possibility of the pharmaceutical industry involvement, medical specialists from different fields now claim the liver-diseased patient. Thus, a specialty or subspecialty in hepatology supported by academic institutions should be established as soon as possible.

The pharmaceutical industry has declared a responsibility to eradicate HCV by creating agreements based on the economy of each country for the marketing of the antiviral drugs. In general, the standard procedure for the pricing of these drugs is to achieve a full refund of the R and D investment in the developed countries, intermediate reimbursement in the middle-income countries, and the possibility to offer a generic product at a lower and accessible cost for the low-income countries (defined as a win-win situation).

Unfortunately, there are still some well-known challenges to overcome in many developing countries, such as corruption and slow bureaucracy to introduce these drugs[55]. Additionally, the lack of precise epidemiological information about HCV infection is an ongoing difficulty.

Another obstacle is performing the diagnostic tests. Each patient should be evaluated before treatment because not all patients that are positive for anti-HCV antibodies have detectable viral loads or have a similar grade of liver damage. Thus, a pretreatment algorithm including initial and follow-up viral loads, genotyping and identification of possible resistance mutations, and staging of liver damage (fibrosis/cirrhosis) should be considered. A conservative estimate of the costs of these tests may exceed up to $2000 to $4000 United States dollars before paying at least $10000 to $80000 United States dollars for a three-month period of treatment[56]. If the patient is a potential non-responder or present with advanced liver damage, this cost may rise even higher.

Considering these conditions several options have been proposed, such as the establishment of non-profit societies that aid in the funding of these high costs for the poor. This creates a risky situation, given the lack of transparency and poor attitudes of some key players previously mentioned, there is a chance that these “non-profit” organizations may end up as personal or family businesses, or in the hand of small groups who are in power.

Nevertheless, with the justification of “supporting updated scientific medical education”, the pharmaceutical companies focus mainly on the treating physicians (clinicians) by selecting medical “leaders”, doctors who have influence among the medical groups or societies, or are representatives of health institutions. Whereas, the few scholars or scientists who are knowledgeable in the field of viral hepatitis are not considered under the argument that they are not clinicians or do not treat patients.

This situation leads to the lost opportunity to be supported by the pharmaceutical industry. Thus, in the absence of proposals and sanitary laws, the pharmaceutical industry is interested in selling their drug; but the academic or research sector in the developing countries do not fall within their scope.