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Volume 7, Issue 4(Suppl) J Gastrointest Dig Syst, an open access journal
ISSN: 2161-069X Gastro Congress 2017
September 11-12, 2017
September 11-12, 2017 | Paris, France
12th Euro-Global Gastroenterology Conference
Cynomolgus monkeys are successfully and persistently infected with HEV-3 after long-term immunosuppressive
therapy
Marcelo Alves Pinto1, Noemi R Gardinali1, Juliana R Guimaraes1, Juliana G. Melgaco1, Yohan B Kevorkian1, Fernanda O Bottino1, Maria Cristina Carlan da
Silva8 , Douglas Pinto2, Heliana Martins2, Gabriel Silveira2, Aline Campos2, Edilson Uiechi 3, Julio Moran4, Renato S Marchevsky5, Oswaldo G Cruz6, Amauri
Alcindo Alfieri7 and Jaqueline M de Oliveira 1
1Instituto Oswaldo Cruz, Brazil
2Serviço de Equivalência e Farmacocinética - Vice-Presidência de Producao e Inovacao em Saúde – VPPIS, Brazil
3Libbs Indústria Farmaceutica, Brazil
4Dr. Julio Moran Laboratories, Switzerland
5Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos, Brazil
6Programa de Computacao Cientifica - Fundacao Oswaldo Cruz, Brazil
7Universidade Estadual de Londrina, Brazil
8Universidade Federal do ABC-UFABC
Epidemiological studies found that hepatitis E virus genotype 3 (HEV-3) infection has been associated with chronic hepatitis and
cirrhosis in immunocompromised patients. Our study aimed to investigate the relationship between the host immunosuppressive
status and the occurrence of HEV-related chronic hepatitis. Here we describe a successful experimental study, using cynomolgus
monkeys previously treated with tacrolimus, a potent calcineurin inhibitor immunosuppressant, and infected with a Brazilian HEV-
3 strain isolated from a naturally infected pig HEV infected monkeys were followed up for 160 days post infection by clinical signs;
virological, biochemical and haematological parameters; tacrolimus blood levels; and liver histopathology. Immunosuppression was
confirmed by clinical and laboratorial findings, such as: moderate weight loss, alopecia, and herpes virus opportunistic infection. In
this study, chronic HEV infection was characterized by the mild increase of liver enzymes serum levels, persistent RNAemia, viral
faecal shedding, and liver histopathology. Three out of four immunosuppressed monkeys showed recurrent HEV RNA detection in
liver samples, evident hepatocellular ballooning degeneration, mild to severe macro and microvesicular steatosis (zone 1), scattered
hepatocellular apoptosis, and lobular focal inflammation. At 69 dpi, liver biopsies of all infected monkeys revealed evident ballooning
degeneration (zone 3), discrete hepatocellular apoptosis, and at most mild portal and intra-acinar focal inflammation. At 160 dpi,
the three chronically HEV infected monkeys showed microscopic features (piecemeal necrosis) corresponding to chronic hepatitis
in absence of fibrosis and cirrhosis in liver parenchyma. Within 4-months after infection, cynomolgus monkeys’ tacrolimus-
immunosuppressed and infected with a Brazilian swine HEV-3 strain induced more severe hepatic lesions progressed to chronic
hepatitis without liver fibrosis, similarly as shown in tacrolimus-immunosuppressed SOT recipients. The cause and effect relationship
between HEV infection and tacrolimus treatment was confirmed in this experiment.
J Gastrointest Dig Syst 2017, 7:4(Suppl)
DOI: 10.4172/2161-069X-C1-053