IN IMMIGRANTS AND NATIVES DISCUSSION AND CONCLUSIONS

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IN IMMIGRANTS AND NATIVES DISCUSSION AND CONCLUSIONS ACUTE HEPATITIS E IN IMMIGRANTS AND NATIVES IN VICENZA, ITALY Maria Teresa Giordani 1, Paolo Fabris 1, Enrico Brunetti 2, Francesca Tamarozzi 2, Luisa Romanò 3 1 Infectious and Tropical Diseases Unit, San Bortolo Hospital, Vicenza, Italy, 2 Division of Infectious and Tropical Diseases, University of Pavia, IRCCS San Matteo Hospital Foundation, Pavia, Italy, 3 Department of Public Health-Microbiology-Virology, University of Milano, Italy. INTRODUCTION Hepatitis E virus (HEV) is the most common agent of acute viral hepatitis worldwide. In developed non-endemic countries the disease has two patterns (1): - imported icteric illness with uncommon secondary cases, and - autoctonous zoonosis from pigs. The two most common genotypes, 1 and 3, are responsible for the two different disease patterns: - genotype 1 waterborne infection through fecally contaminated drinking water, - genotype 3 zoonotic. The disease is generally a self-limiting acute hepatitis followed by complete recovery, but pregnant women, immunocompromised patients and patients with pre-existing chronic liver diseases have a high risk of mortality. A possible role of HEV in causing chronic hepatitis in the immunocompromised host was reported recently (4). No treatment is available at the moment. Anti HEV + Italy: 2,6% Figure 2. Etiology of acute viral hepatitis in Vicenza, Italy (1995-2010). * Dengue (2 cases), Smallpox (1 case) Figure 1. Worldwide distribution of HEV infection. PATIENTS AND METHODS Anti-HEV IgG and IgM were determined by different immunoassays. Serum and stool samples were analyzed for the presence of the viral RNA by nested RT-PCR. Briefly, viral RNA was extracted from a 10% fecal suspension of from serum using QIAamp MinElute Virus Spin Kit (QIAGEN, Germany). HEV-RNA was detected by nested RT-PCR employing primers from ORF1 and ORF2 of the viral genome. To determine the HEV genotype, the amplicons were directly sequenced and submitted to a phylogenetic analysis. Table 1. Patients characteristics. Age (Y) Media + SD Range 30.25 + 4.9 (18-42) Gender M/F 17/3 Country of origin -Bangladesh -India -Pakistan -Italy Time of stay in Italy (if immigrant) < 1 months 1-3 years 3-6 years 6-9 years > 9 years Employement workman housewife Hay trader (autoct. case) 15 3 1 4 2 5 8 16 AIM of the STUDY To investigate the epidemiological and clinical characteristics of 20 cases of acute HEV hepatitis in Vicenza, Italy (1995-2009). RESULTS Secondary case: the patient immigrated from Bangladesh 9 years before developing HEV acute hepatitis in March 2005. He did not travel to his country of origin since August 2004. An household contact had HEV acute hepatitis in November 2005. Stool of the household contact were positive for HEV RNA. Autoctonous case: one 35-years old patient developed icteric acute hepatitis in 1995. He had never traveled outside Italy. Serology was positive for specific IgG and IgM, however HEV RNA was not detected in biological samples, therefore no genotyping was performed. A zoonotic transmission was suspected for professional reasons (he trades hay and is in contact with farms) Table 2. Liver function parameters at peak, ultrasonographical aspects and other clinical data Table 3. Virological results. * HEV genotype was determined in 9 patients; all of them resulted of genotype 1. GPT (UI/L) MEAN +SD RANGE 2837 + 369.5 (751-6826) Total Bilirubin (mg/dl) mean + SD Range 8.6 + 5,2 (2,5-23,9) ALP (UI/L) mean + SD 207.45+ 68,6 (117-440) Ggt (UI/L) mean +SD 146 + 73 (59-464) Ultrasound -hepatic enlargement -thickening of gallbladder wall -presence of hylum lymphnodes -splenic enlargement 20/20 12/20 11/20 10/20 Comorbilities -thyphoid fever (1/20) -Isospora belli diarrhoea (1/20) -HBsAg + (inactive carrier, HBV-DNA negative) (1/20) Anti-HEV IgG Anti-HEV IgM HEV-RNA SERUM HEV-RNA STOOL Positive samples 20/20 (100%) 17/20* (85%) 13/20 * (65%) Negative samples 3/20 (15%) Not done 4/20 (20%) DISCUSSION AND CONCLUSIONS HEV is present in the Vicenza area, with few diagnosed cases per year since 1995 (2). The number of reported cases increased since 2004: 0.13 cases/105/year in 1995-2003 vs 0.22 cases/105/year in 2004-2009. The clinical course, sonographic appearance and biochemical profile of HEV acute hepatitis do not differ from those of other common causes of acute viral hepatitis. All but one patients imported the infection from epidemic-endemic areas of Asia and one secondary case occurred in this community. Because of the risk of transmission of HEV within and outside the immigrant communities, in particular for pregnant women and patients with hepatic diseases or immunodepression, there is a need for a fast diagnosis and effective prevention of secondary cases. Immigrants are particularly at risk to develop acute hepatitis E after visiting the country of origin and this risk appears to increase with the length of stay in Italy, suggesting a loss of previously acquired immunity (3). References Teshale EH, Hu DJ, Holmberg SD.The two faces of hepatitis E virus.Clin Infect Dis. 2010 Aug 1;51(3):328-34. Zanetti AR, Schlauder GG, Romanò L, Tanzi E, Fabris P, Dawson GJ, Mushahwar IK. Identification of a novel variant of hepatitis E virus in Italy. J Med Virol. 1999 Apr;57(4):356-60. Chandra V, Taneja S, Kalia M, Jameel S. Molecular biology and pathogenesis of hepatitis E virus. J Biosci. 2008 Nov;33(4):451-64. Review. Dalton HR, Bendall R, Ijaz S, Banks M. Hepatitis E: an emerging infection in developed countries. Lancet Infect Dis. 2008 Nov;8(11):698-709. Review. Clemente-Casares P, Pina S, Buti M, Jardi R, MartIn M, Bofill-Mas S, Girones R. Hepatitis E virus epidemiology in industrialized countries. Emerg Infect Dis. 2003 Apr;9(4):448-54.