Hepatitis E virus (HEV) is considered an agent responsible for acute hepatitis that does not progress to chronic hepatitis. We identified 14 cases of acute HEV infection in three patients receiving liver transplants, nine receiving kidney transplants, and two receiving kidney and pancreas transplants. All patients were positive for serum HEV RNA. Chronic hepatitis developed in eight patients, as confirmed by persistently elevated aminotransferase levels, serum HEV RNA, and histologic features of chronic hepatitis. The time from transplantation to diagnosis was significantly shorter and the total counts of lymphocytes and of CD2, CD3, and CD4 T cells were significantly lower in patients in whom chronic disease developed.

Using a validated sensitive assay, we found hepatitis E virus (HEV) IgG in 52.5% of voluntary blood donors in southwestern France. This fi nding suggests HEV is highly endemic to this region. The high HEV prevalence may refl ect local dietary practices, such as eating uncooked pork and game products. It is now recognized that hepatitis E virus infection is not confi ned to developing countries. HEV infection is a growing public health concern in industrialized countries where the disease is mainly autochthonous, caused by HEV genotypes 3 (Europe) and 4 (People's Republic of China and Japan), and is thought to be zoonotic (1).In a previous study, we estimated that 16.6% of blood donors in the Midi-Pyrénées region of southwestern France have HEV antibodies (2). This rate was much higher than that measured in northern France (3), which suggests differences between these 2 populations and their exposure to HEV that we wished to explore further. However, it is diffi cult to make wider comparisons with seroprevalence studies from other areas because the various assays used differed in sensitivity and specifi city (4). Because a recent study suggested that the HEV IgG assay we used in our original study lacks sensitivity (5), we repeated and extended the study using a more sensitive assay that has been validated by using serum from PCR-proven HEV genotype 3 infections (5). The StudyDuring September 2003 through May 2004, serum samples were collected from 512 adult blood donors 18-64 years old (median 42 years) and 188 children 2-4 years old. The blood donors were unpaid voluntary donors; the children were hospitalized in Toulouse for surgery or trauma. All were residents of the Midi-Pyrénées region. The prevalence of HEV IgG was determined by using the Wantai HEV IgG enzyme immunoassay (Wantai Biologic Pharmacy Enterprise, Beijing, People's Republic of China), according to the manufacturer's instructions. Details of baseline demographic data and putative risk factors were collected from blood donors by using a structured questionnaire. In addition, to assess the risk for foodborne infection, we tested 18 local pig-liver sausages for HEV RNA using a quantitative real-time PCR based on the open reading frame 2 region of the HEV genome (6).HEV IgG was detected in 268 (52.5%) of 512 (95% confi dence interval [CI] 48.2%-56.8%) of the blood donors. Seroprevalence increased with age ( Figure 1). The ranges of optical density/cutoff ratios for positive and negative samples showed a clear bimodal distribution (Figure 2). Of 244 rural donors, 63.1% (95% CI 57%-69.2%) were anti-HEV positive compared with 42.9% (95% CI 37-48.8) of 268 urban donors (p<0.01). For children, seroprevalence was 3.7% (95% CI 1.0%-6.5%). The mean ± SD optical density/cutoff ratio of the positive samples was 5.43 ± 3.93 for children and 5.99 ± 3.52 for adults. Although several factors were associated with the presence of HEV IgG after univariate analysis, multivariate analysis identifi ed only age, rural residence, hunting, and contact with cats as factor...

Fulminant hepatitis E has not been well characterized in industrialized countries. The aim of this study was to prospectively describe patients with acute hepatitis E presenting as fulminant hepatic failure, i.e. with encephalopathy and prothrombin index <50%. Between February 1997 and April 2005, seven patients with encephalopathy were diagnosed with acute hepatitis E using viral RNA detection. These patients were compared with 33 patients diagnosed with a mild form (absence of encephalopathy) of acute hepatitis E during the same time period. Patients were 65 +/- 11 years old. Five were active drinkers and six had chronic liver disease. All hepatitis E virus sequences evaluated (5/7) were of genotype 3. All patients but two died (71%). Four patients had no travel history. When compared with patients with a mild form of acute hepatitis E, active alcohol abuse and chronic liver disease were more frequent in patients with the severe form. Duration of hospitalization was longer. Aspartate transferase and bilirubin levels were significantly higher. Prothrombin index and accelerin levels were lower and death was more frequent. Acute nontravel-associated hepatitis E can appear as fulminant hepatitis with encephalopathy and coagulation disorders. Prognosis is severe and this may be due to the age at which it occurs and frequent underlying chronic liver disease.

Agence de la Biomédecine/Agence Régionale de Santé de la Guadeloupe/Inserm-REACTing.

The outbreak of the Zika Virus (ZIKV) and its association with fetal abnormalities have raised worldwide concern. However, the cellular tropism and the mechanisms of ZIKV transmission to the fetus during early pregnancy are still largely unknown. Therefore, we ex vivo modeled the ZIKV transmission at the maternal-fetal interface using organ culture from first trimester pregnancy samples. Here, we provide evidence that ZIKV strain circulating in Brazil infects and damages tissue architecture of the maternal decidua basalis, the fetal placenta and umbilical cord. We also show that ZIKV replicates differentially in a wide range of maternal and fetal cells, including decidual fibroblasts and macrophages, trophoblasts, Hofbauer cells as well as umbilical cord mesenchymal stem cells. The striking cellular tropism of ZIKV and its cytopathic-induced tissue injury during the first trimester of pregnancy could provide an explanation for the irreversible congenital damages.

Immunocompromised patients should avoid eating insufficiently cooked game meat or pork products so as to reduce the risk of HEV infection and chronic liver disease.

Infections with hepatitis E virus (HEV) in solid-organ transplant recipients can lead to chronic hepatitis. However, the incidence of de novo HEV infections after transplantation and risk for reactivation in patients with antibodies against HEV before transplantation are unknown. Pretransplant prevalence of these antibodies in 700 solid-organ transplant recipients at Toulouse University Hospital in France was 14.1%. We found no HEV reactivation among patients with antibodies against HEV at the first annual checkup or by measuring liver enzyme activities and HEV RNA. In contrast, we found 34 locally acquired HEV infections among patients with no antibodies against HEV, 47% of whom had a chronic infection, resulting in an incidence of 3.2/100 person-years. Independent risk factors for HEV infection were an age <52 years at transplantation and receiving a liver transplant. Effective prophylactic measures that include those for potential zoonotic infections should reduce the risk for HEV transmission in this population.

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