Detection and characterization of hepatitis E virus genotype 3 in HIV-infected patients and blood donors from southern Brazil.

BACKGROUND: Hepatitis E virus genotype 3 (HEV-3) infection usually causes self-limited acute hepatitis. In immunosuppressed patients, HEV-3 infection can rapidly progress to chronic hepatitis and cirrhosis. In southern Brazil, data on HEV seroprevalence are scarce. METHODS: Testing for HEV RNA and antibodies (anti-HEV) was performed for 320 HIV-infected patients followed at the HIV/AIDS Service of the Federal University of Rio Grande between 2012 and 2013, as well as 281 blood donor samples obtained in 2015. Variables associated with anti-HEV positivity were assessed by multivariable logistic regression analysis. RESULTS: HIV and blood donor groups showed similar HEV seroprevalence (6.7% and 7.1%, respectively). Risk factors associated with anti-HEV detection were older age, marital status, a higher number of sexual partners, poor sanitation, and alcohol use (HIV group), and living in a rural area (blood donors). HEV RNA was detected in eight serum samples from HIV-infected patients and in one blood donor, who was also positive for anti-HEV IgM and IgG. CONCLUSIONS: The prevalence rates of HEV infection were comparable between HIV-seropositive patients who were not severely immunocompromised and blood donors. The blood donor's HEV isolate showed high similarity with swine HEV strains from Brazilian herds in the same region, thus indicating a potential risk of foodborne and parenteral transmission via blood transfusion.

Cynomolgus monkeys are successfully and persistently infected with hepatitis E virus genotype 3 (HEV-3) after long-term immunosuppressive therapy.

Epidemiological studies found that hepatitis E virus genotype 3 (HEV-3) infection was 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 naturally infected pigs. HEV infected monkeys were followed up during 160 days post infection (dpi) by clinical signs; virological, biochemical and haematological parameters; and liver histopathology. The tacrolimus blood levels were monitored throughout the experiment. 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 RNA viremia and 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 follow up, the tacrolimus-immunosuppressed cynomolgus monkeys infected with a Brazilian swine HEV-3 strain exhibited more severe hepatic lesions progressing to chronic hepatitis without liver fibrosis, similarly as shown in tacrolimus-immunosuppressed solid organ transplant (SOT) recipients. The cause-effect relationship between HEV infection and tacrolimus treatment was confirmed in this experiment.