The history of hepatitis E virus (HEV) as a causative agent of hepatitis is linked to Mexico. In 1986, one of the first recognized virus outbreaks in Latin America related to enterically transmitted viral non-A, non-B (NANB) hepatitis occurred in this country. Serological studies of the expressed proteins from cDNA obtained from viral RNA recovered from this outbreak did show specific reactions with sera from patients from enterically transmitted viral NANB hepatitis outbreaks identified in Asia; this finding supported the notion that the outbreaks in Mexico and those identified in Asia were caused by the same etiological agent. In the early 1990s, a comparison of complete sequences of Burma, Pakistan and Mexico strains, the only available at that time, led to the identification of a new virus called hepatitis E virus as the causative agent of the outbreaks in Asia and Mexico.
The analysis of available sequences led to the first description of genotype 2 (Gt2) from the Mexican ‘isolates that became the strain reference for this genotype at that time, until another sequence of HEV-Gt2 obtained from stored stool samples collected in Mexico was published and became the reference sequence for HEV-Gt2a. In addition to causing outbreaks in Mexico, HEV-Gt2 has been found in countries on the African continent. Therefore, the HEV-Gt2 distribution seems to be restricted to specific regions. Diverse possibilities might be related to the relatively low frequency reported for HEV-Gt2 worldwide; its finding in regions with precarious sanitary conditions where a lack of hepatitis E surveillance prevails is an important aspect to be considered. Indeed, no new findings of HEV-Gt2 have been reported in Mexico in the last thirty-seven years, which might be related to the null systems for monitoring hepatitis E in the country.
HEV was almost forgotten in Mexico since after the outbreaks in the 1980s, no molecular studies on human infections were performed until 2018, when HEV genotype 1 (HEV-Gt1) was identified in pediatric patients with acute hepatitis, and one year later, HEV genotype 3 (HEV-Gt3) was reported from the retrospective analysis of samples from patients with chronic liver disease. Additionally, from the study of animal reservoirs, HEV-Gt3 with zoonotic capability was originally identified in 2015 using sera/fecal samples from farm swine, and the same genotype was identified in livers from pigs in 2013. Recently, complete genome sequencing of one sample confirmed HEV-Gt3 circulation in swine.
With the finding of three genotypes (HEV-Gt1, -Gt2 and-Gt3), Mexico is unique in America. Unfortunately, the information related to this virus is limited to studies from independent research groups. Diverse investigations have identified a high frequency of anti-HEV antibodies in specific populations, reaching higher frequencies in patients with liver disease and in the setting of rural areas. However, since all reports come from distinct geographic regions and Mexico is a country with a plethora of realities (from very rich areas and low-income, densely populated areas in the cities to very poor rural communities), a well-designed hepatitis E surveillance system is needed to have a real picture of the infection. In this regard, the study of sources of the virus is crucial to avoid its dissemination. Moreover, monitoring circulating strains is important, and the implementation of guidelines for the detection, diagnosis, and management of patients, particularly those at risk of developing chronic infection, is imperative.
In Mexico, we use to say that “he seeks finds”. We cannot stop seeking HEV in this country with conditions predisposing it to hepatitis E prevailing.
By: Nora A. Fierro, PhD; Principal Investigator; Instituto de Investigaciones Biomédicas; Universidad Nacional Autónoma de México.
Read the full review: Viera-Segura O, Calderón-Flores A, Batún-Alfaro JA, Fierro NA. Tracing the History of Hepatitis E virus Infection in Mexico: From the Enigmatic Genotype 2 to the Current Disease Situation. Viruses. 2023 Sep;15(9):1911-1926.
