1. Hepatitis E in Italy Site:Institute of Virology, University of Milan Period: Period:January 1994 – December 2001 Study population: Study population:310 patients with acute nAnC hepatitis (negativity for IgM anti-HAV, HBsAg, IgM anti-HBc, anti-HCV, HCV-RNA and exclusion of autoimmunity, alchol or hepatotoxic drugs) ALT at the hospitalization: ALT at the hospitalization: mean 1451.3 IU/ml median 1100 IU/ml range 101-12290 IU/ml

2. Samples examined:at least two sera collected during the acute and convalescent phase of the illness and stools. Anti-HEV IgG: Anti-HEV IgG:EIA (Abbott Labs) Anti-HEV IgM: Anti-HEV IgM: in house EIA HEV RNA: HEV RNA:nested RT-PCR ORF3 ORF2 ORF1 nt 55nt 320 SAMPLES AND METHODS

3. Acute hepatitis E: definition Hepatitis E was defined by the presence of HEV-RNA in sera and/or stools; positivity for IgM anti-HEV and/or seroconversion to IgG anti-HEV. To identify the risk factors for hepatitis during the 6m preceeding the onset of the illness, each patient was interviewed with a pre-coded questionnaire.

4. Hepatitis E in Italy: Results (1) 44/310 (14.2%) patients with acute hepatits E mean age 29.7, range 3 - 65 years 36 males, 8 females Risk factors: Unknown Contact with an infected person Travel to: 77.3% 20.4% 2.3% India Pakistan Bangladesh Marocco Somalia Angola Sri Lanka

5. Phylogenetic tree (unrooted) of 14 viral strains from patients with acute hepatitis E US2 US1 swUS1 Italia1 Ct1 Mx1 I1 C2 C3 C1 C4 Pak1 I2 B2 B1 INDIA BANGLADESH PAKISTAN Group I Group IV Group II Group III Hepatitis E in Italy: Results (2)

6. Hepatitis E in Italy: conclusions HEV is the aetiological cause in approx 14% of HEV is the aetiological cause in approx 14% of patients with acute nAnC hepatitis, 95% exhibiting a benign course. Hepatitis E is generally diagnosed in travellers Hepatitis E is generally diagnosed in travellers from endemic areas. The identification of a new variant in an The identification of a new variant in an individual who never indicated travel or contact with individuals associated with endemic areas, suggest that this virus may be native to Italy.