think that the advent of a rapid point-of-care test that can be performed without requiring phlebotomy needs to be recognized as a major breakthrough in the field. Its implementation in a broadened screening program cou- pled with a decrease in drug costs, as the consequence of an agreement between local health systems and pharma- ceutical companies, could soon force us to revise some (pre)concepts in the diagnosis of HCV infection. ALESSIO AGHEMO MASSIMO COLOMBO First Division of Gastroenterology Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Università degli Studi di Milano Milan, Italy A VACCINE FOR HEPATITIS E: HAS IT FINALLY ARRIVED? Zhu F-C, Zhang J, Zhang X-F, et al. (Jiangsu Provincial Center for Disease Control and Prevention, Manjing Province, China). Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, ran- domized, double-blind placebo-controlled, phase 3 trial. Lancet 2010;376:895–902. The study by Zhu et al was a randomized, double- blind, placebo-controlled, phase III trial. The aim of this trial was to assess the efficacy and safety of the recombi- nant hepatitis E virus (HEV) vaccine, HEV 239, in the general population. This double-blind, randomized, pla- cebo-controlled trial was done in Dongtai County, Ji- angsu Province, China, a region where both genotypes 1 and 4 co-circulate, with the zoonotic genotype 4 predom- inating (Lancet 2010;376:895–902). The HEV 239 vaccine contained 30 g of the purified antigen adsorbed to 0.8 mg aluminium hydroxide sus- pended in 0.5 mL buffered saline. A hepatitis B vaccine containing hepatitis B virus surface antigen in 0.5 mL aluminium hydroxide was used as placebo. Three doses of vaccine or placebo were given intramuscularly at 0, 1, and 6 months. Men and women were eligible for enrol- ment if they were healthy, aged 16 – 65 years, and under- stood the study procedures. A sentinel hepatitis surveillance system was set up to identify incident hepatitis cases. A case of hepatitis was defined as a patient presenting with constitutional symp- toms such as fatigue, loss of appetite, or both for longer than 3 days with alanine aminotransferase (ALT) 2.5 times the upper limit of the range for normal. Patients with abnormal concentrations of ALT were tested for immunoglobulin (Ig)M hepatitis A virus, hepatitis B vi- rus surface antigen, hepatitis B virus core protein IgM, IgM hepatitis C virus, and IgM HEV. Paired serum sam- ples were obtained from these patients at the time of presentation and 2– 6 weeks later. Serial samples were tested for IgM and IgG HEV, HEV RNA, and IgM hepa- titis A virus. Serum samples of patients with detectable IgM HEV or a 2 times rise of IgG HEV in paired samples were tested for HEV RNA. A participant was defined as an acute hepatitis E patient if she or he had an acute illness lasting for 3 days; abnormal serum ALT concentration 2.5 times the upper limit of normal range; and positive IgM HEV IgM and RNA, 4 times increase in IgG HEV, or both. Serum samples were taken from participants before the first vaccine dose and 1 month after the third dose, and antibody response was defined as a 4-fold increase of HEV IgG in an individual’s paired sera. The primary end point was prevention of hepatitis E in participants who received 3 doses of vaccine (ie, the per-protocol population) during the 12 months from the 31st day after receipt of the third dose. The study region was endemic for infection with HEV, with nearly half the participants tested on day 0 being seropositive (11,165 of the trial participants were tested for HEV IgG, of whom 5285 [47%] were seropositive for HEV). Participants were randomly assigned to vaccine (n = 56,302) or placebo (n = 56,302) and were followed up for 19 months. There were 48,693 (86%) participants in the vaccine group and 48,663 participants (86%) in the placebo group who received 3 vaccine doses and were included in the primary efficacy analysis. There were 23 cases of hepatitis E during the follow-up, 1 in the vaccine group (the participant received 1 dose of the vaccine) and 22 in the placebo group. Vaccine efficacy for participants who received 1 dose was 95.5% (95% confidence interval [CI], 66.3–99.4). Five participants developed hepatitis E during the 14 days after the second dose and before the third dose; all were in the placebo group. Vaccine efficacy after 2 doses was 100%. In the primary analysis of the population, 15 participants developed hepatitis E during the 12 months from the 31st day after receipt of the third dose; all 15 were in the placebo group. Vaccine efficacy against hepatitis E was 100.0% (95% CI, 72.1–100.0), and protection extended to all participants throughout the 12 months. Most adverse events were mild. Rates of serious adverse events were similar in the vaccine and placebo groups during the entire follow-up, and none were deemed to be related to vaccination. Serum samples were taken from 11,165 participants before vaccination and 1 month after receipt of the third dose. The 5494 (98.7%) of 5567 participants in the vac- cine group had an increase in antibody concentration in the samples after vaccination of 4 times from that of the corresponding samples before vaccination. By con- trast, 119 (2.1%) of 5598 participants in the placebo group showed an antibody response and all the episodes were subclinical infection. Of the 13 patients whose viruses were isolated for sequencing, 12 had genotype 4 and 1 had genotype 1. Of April 2011 SELECTED SUMMARIES 1349