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Hepatitis E Virus: Still an Enigma in Mexico
Mauricio Realpe-Quintero*, Oliver Viera-Segura**, Nora A. Fierro**,
Corresponding author
noraalma@gmail.com

Correspondence and reprint request:
* Laboratory of Biological Development, Veterinary Hospital of Small Species, University Center of Biological and Agricultural Sciences, University of Guadalajara, Mexico
** Immunovirology Unit, Molecular Biology Service, Civil Hospital of Guadalajara Fray Antonio Alcalde, Center University of Health Sciences, University of Guadalajara, Mexico
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Hepatitis E virus &#40;HEV&#41; is a single-stranded RNA virus that is an important cause of acute and self-limitating hepatitis and could lead to fulminant liver failure in the setting of pregnancy&#46; Additionally&#44; in immunosuppressed patients&#44; HEV may cause chronic infection with the development of sequels including fibrosis and cirrhosis&#46; Worldwide&#44; HEV has been also associated with extrahepatic manifestations such as neurological and renal disease&#46; In spite of that&#44; HEV remains poorly characterized and is frequently unidentified or misdiagnosed by clinicians&#46; Although fecal-oral route is the most common via of HEV transmission&#44; HEV can be also vertically transmitted from infected mothers to their fetuses&#46; HEV may spread by zoonotic transmission from infected animals to humans and through person-to-person contact&#46; Moreover&#44; HEV is now recognized as a potentially transfusion-transmitted virus&#46; Currently&#44; it is estimated that there are more than 20 million HEV infections every year worldwide&#44; leading to 3&#46;3 million symptomatic cases and more than 56&#44;000 deaths&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">HEV is highly distributed in the globe and has been described with at least 8 genotypes circulating in different species&#46; Genotypes 1 and 2 have exclusively been found in humans&#44; whereas genotype 3 and 4 are zoonotic in nature and are detected in humans and more frequently in animals such as pigs&#44; deers&#44; and boars&#46; Limited sequences of genotypes 5&#8211;8 are currently available and are detected in other mammals&#46; It is accepted that manifestation of HEV disease&#44; source of infection&#44; and route of transmission vary by genotype&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Thus&#44; accurate identification and diagnosis of HEV has important implications for patient management&#44; disease control&#44; epidemiology&#44; and characterization of transmission mechanisms&#46;</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Viral Hepatitis and Liver Disease in Mexico</span><p id="p0015" class="elsevierStylePara elsevierViewall">In the last years&#44; the rates of liver disease have been increasing in Mexico&#46; Alcohol consumption together with hepatitis A&#44; B and C viruses &#40;HAV&#44; HBV and HCV&#41; infections and non-alcoholic liver disease &#40;NAFLD&#41; are the main etiologies described in the country as associated to liver disease&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="p0020" class="elsevierStylePara elsevierViewall">Despite public efforts&#44; Mexico has the highest rate of deaths in Latin America due to liver cirrhosis&#44; with more than 30&#44;000 deaths per year&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Long-term projections of the disease suggest that by the year 2030 the number of cases related to liver deaths in Mexico will increase by 55&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Altogether suggests that the public policies that have been considered in the country still require close revision in order to contend with the main liver pathologies affecting the Mexican population&#46;</p><p id="p0025" class="elsevierStylePara elsevierViewall">According to the local government health agency &#40;Secretaria de Salud&#44; SSA in Spanish&#41;&#44; most of the cases of reported liver injury with no aetiological agent have been attributed to NASH&#46; However&#44; the SSA does not report the epidemiological status of HEV associated disease&#46; Hence&#44; HEV could represent a no-sufficiently attended hepatic infection&#44; which could be related with up to 13&#46;4&#37; of viral hepatitis in the country without an aetiological agent detected in 2017&#44; as reported by SSA in Mexico&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Hev in Mexico</span><p id="p0030" class="elsevierStylePara elsevierViewall">On the basis of an outbreak of acute infection by HEV between 1986&#8211;1987 in central Mexico and the first identification of viral genotype 2 in those samples&#44; the country has been considered as an hyperendemic zone&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> However&#44; thirty-one years since first detection in Mexico&#44; no new reports on genotype 2 have been published or data has been made available from government or public sources&#46; In Mexico&#44; in addition to genotype 2&#44; genotype 3 has also been reported in animals&#46; The first report from 2005 in swine was complemented in 2012 with a report of seroconversion in deers&#44; and more recently confirmed after studies in farming pigs intended to human consumption&#46; Also&#44; a high seroprevalence report of HEV in samples from cirrhotic patients from western Mexico with no other aetiological agent is available&#44; and the highest seroprevalence of HEV in farmed pigs has been found in western Mexico&#44; compared to the rest of country&#46; Based on these findings&#44; the expected seroprevalence and risk of HEV infection in humans in Mexico is rather high&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> as recently reported in HAV-HEV co-infected pediatric patients exhibiting acute hepatitis&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Within Mexico&#44; research studies suggest a variable seroprevalence of HEV in humans depending on the geographical regions analyzed&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Furthermore&#44; the frequent detection of HEV-specific antibodies in samples of people with no history of hepatitis suggests underestimation of the local disease burden&#44; and uncertainty on the actual impact that HEV infection could represent in Mexico&#46;</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Treatment</span><p id="p0035" class="elsevierStylePara elsevierViewall">Limited information is known regarding specific treatments against HEV infection&#46; This information is already available for endemic regions such as India and&#44; no guidelines have been proposed for Mexico&#46; So far&#44; no specific drug has been approved for the treatment of infection based on World Health Organization &#40;WHO&#41; recommendations&#46; Lowering the dose of immunosuppressive drugs and administration of ribavirin has been suggested to treat immunocompromised individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> However&#44; taking into account that only 50&#37; of HEV infections in immunosuppressed transplant recipients lead to chronic HEV infection&#44; this choice has to be revised&#46; Studies in specific populations should be conducted in order to identify pharmacological approaches of benefit for patients&#46;</p><p id="p0040" class="elsevierStylePara elsevierViewall">Since 2012&#44; an effective vaccine is available in China&#59; however&#44; there is still no data on the efficacy of this vaccine in other endemic regions of the world&#46;</p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Recommendations</span><p id="p0045" class="elsevierStylePara elsevierViewall">Considering the recommendations given by the WHO to eradicate infectious hepatitis by 2030&#44; joined efforts are required in order to assess and better know the disease burden due to HEV&#44; particularly in those geographical regions where infection is considered endemic such as Mexico&#46;</p><p id="p0050" class="elsevierStylePara elsevierViewall">With the mission of improving diagnosis and general management of HEV infections&#44; having virus eradication as the ultimate goal&#44; the following recommendations could be followed&#58;<ul class="elsevierStyleList" id="l0005"><li class="elsevierStyleListItem" id="u0005"><span class="elsevierStyleLabel">&#8226;</span><p id="p0055" class="elsevierStylePara elsevierViewall">To implement the use of NAT-based assays for HEV RNA detection in Mexico with the aim of harmonizing detection methods to globally available standards&#46;</p></li><li class="elsevierStyleListItem" id="u0010"><span class="elsevierStyleLabel">&#8226;</span><p id="p0060" class="elsevierStylePara elsevierViewall">To study the genomic variability of the virus in general population&#44; high risk populations&#44; including pregnant women&#44; immunosuppressed patients&#44; children&#44; patients with NASH&#44; patients with chronic infection with HBV and HCV&#44; and patients with high alcohol consumption&#46; This is in order to identify specific risk population in Mexico&#46;</p></li><li class="elsevierStyleListItem" id="u0015"><span class="elsevierStyleLabel">&#8226;</span><p id="p0065" class="elsevierStylePara elsevierViewall">To analyze the origin and transmission of HEV infections in Mexico in order to identify chains of transmission&#46; The systematic study to identify the risk represented by water&#44; particularly in areas considered to have poor health conditions and deficient sanitary treatment of the water&#44; is required&#46; Moreover&#44; the risk of blood banking as a source of HEV infection requires to be tested in Mexico&#44; as already done in other regions&#46;</p></li><li class="elsevierStyleListItem" id="u0020"><span class="elsevierStyleLabel">&#8226;</span><p id="p0070" class="elsevierStylePara elsevierViewall">Finally&#44; it is imperative to increase awareness for HEV associated disease amongst health care practitioners&#44; as well as including HEV information as part of health teaching programs for the general population&#46; Increasing flow of information related to risk factors for HEV infection for educational purposes to general public&#44; and to health-care professionals&#44; is an urgent necessity in order to cope with the particular epidemiological situation in Mexico&#46;</p><p id="p0075" class="elsevierStylePara elsevierViewall">Altogether&#44; these recommendations might be extended to other endemic regions<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and could be translated in strategies intended to improve general disease management&#44; and to implement locally preventive and controlling programs to contend and limit the spreading of this enigmatic virus&#46;</p></li></ul></p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Acknowledgements</span><p id="p0080" class="elsevierStylePara elsevierViewall">The authors thank to Diana Jennifer Carrillo-Casillas and Jose David Ramos-Solano for editing the manuscript&#46;</p></span></span>"
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ISSN: 16652681
Original language: English
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