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      Long-Term Persistence of Seroprotection by Hepatitis B Vaccination in Healthcare Workers of Southern Italy

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          The impact of hepatitis B virus (HBV) vaccination campaigns on HBV epidemiology needs to be evaluated, in order to assess the long-term immunity offered by vaccines against HBV.


          To evaluate the current status of anti-HBV vaccine coverage among healthcare workers (HCWs) in Southern Italy, and to determine the long-term persistence of antibodies to hepatitis B surface antigens (anti-HBs) in such a cohort of subjects.

          Patients and Methods

          A longitudinal, retrospective seroepidemiological survey was conducted among 451 HCWs, who were working at or visiting, the Occupational Health Department of a city hospital, in Catania, Italy, between January 1976 and December 2010.


          At the 30-year follow-up (mean follow-up 10.15 ± 5.96 years, range 0.74-30), 261 HCWs had detectable anti-HBs titers indicating a persistence of seroprotection of 89.4% (out of 292 anti-HBs positive results, three months after vaccination). An inadequate vaccination schedule was the strongest predictor of antibody loss during follow-up (OR = 8.37 95% CI: 5.41-12.95, P < 0.001). A Kaplan-Maier survival curve revealed that the persistence of anti-HBs 30 years after vaccination, was 92.2% for high responders, while it was only 27.3% for low responders (P = 0.001).


          A good level of seroprotection persisted in 57.9% of the subjects after 30 years. Factors related to this immunization status confirmed the importance of vaccinating HCWs early in their careers and ensuring an adequate vaccination schedule. However, with particular reference to the low rate of hepatitis B vaccine coverage among HCWs in Southern Italy, the implementation of a new educational intervention as part of an active vaccination program is needed.

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          Most cited references 46

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          Are booster immunisations needed for lifelong hepatitis B immunity? European Consensus Group on Hepatitis B Immunity.

          Long-term protection against clinically significant breakthrough hepatitis B (HB) virus infection and chronic carriage depends on immunological memory, which allows a protective anamnestic antibody response to antigen challenge. Memory seems to last for at least 15 years in immunocompetent individuals. To date there are no data to support the need for booster doses of HB vaccine in immunocompetent individuals who have responded to a primary course. All adequately vaccinated individuals have shown evidence of immunity in the form of persisting anti-HBs and/or in vitro B-cell stimulation or an anamnestic response to a vaccine challenge. Nonetheless several countries and individuals currently have a policy of administering booster doses to certain risk groups. Boosters may be used to provide reassurance of protective immunity against benign breakthrough infection. For immunocompromised patients, regular testing for anti-HBs, and a booster injection when the titre falls below 10 mIU/mL, is advised. Long-term monitoring should continue, to confirm the absence of clinically significant breakthrough episodes of hepatitis B and to find out if a carrier state develops after 15 years. Also, non-responders to a primary course should continue to be studied.
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            Vaccine induced immunologic memory for hepatitis B surface antigen: implications for policy on booster vaccination.

            This paper reviews published literature on the long-term persistence of immunologic memory for HBsAg after a course of hepatitis B vaccine and the functional significance this has for policy on booster vaccination. Several studies have shown that vaccine induced antibody (anti-HBs) specific for the surface antigen (HBsAg) of hepatitis B virus (HBV) is protective at a serum concentration of 10 milli-International Units per milliliter (mIU ml-1). When acquired passively (e.g. from hepatitis B immune globulin), susceptibility to infection returns as antibody declines. However, vaccine induces active synthesis of anti-HBs accompanied by immunologic memory for HBsAg that affords ongoing protection independent of antibody. Persistent memory over periods of 5 years or more is evident from large, rapid increases in antibody following booster vaccination, even in subjects who have lost antibody. Complementary studies, using an in vitro enzyme linked immunosorbent assay (spot-ELISA), show that the number of memory B lymphocytes able to produce anti-HBs does not diminish as the level of antibody declines. That immunologic memory provides effective immunity is suggested by serologic studies over periods of 5 years or more of vaccinees frequently exposed to HBV. Although many failed to maintain at least 10 mIU ml-1 of antibody, there have been very few clinically significant breakthrough infections. Thus, it appears unnecessary to give healthy vaccinees a booster vaccination when the level of anti-HBs falls below 10 mIU ml-1. Current studies suggest good retention of immunologic memory in healthy vaccinees over periods of 5-12 years. While additional studies will better define the limits of this phenomenon, routine booster vaccination should not be needed to sustain immunologic memory and protection within 5 years and perhaps longer after the primary vaccination series.
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              Chronic hepatitis D: a vanishing Disease? An Italian multicenter study.

              Hepatitis delta virus (HDV) was responsible for a high proportion of cases of acute and chronic liver disease in Southern Europe during the 1970s. Some data suggest that by the 1990s HDV circulation had substantially declined. We have assessed the prevalence of HDV infection and its clinical impact in 834 Italian hepatitis B surface antigen (HBsAg) carriers in 1997. Anti-HDV antibodies were sought in all consecutive chronic HBsAg carriers observed in 14 referral liver units throughout Italy. Risk factors for anti-HDV positivity were evaluated. Anti-HDV antibodies were found in 69 of 834 (8.3%) HBsAg-positive patients. Cohabitation with an anti-HDV-positive subject, intravenous drug addiction, residence in the South of the country, and the presence of cirrhosis were independently associated with the presence of anti-HDV antibodies. The overall prevalence of anti-HDV antibodies was lower than those observed in 2 multicenter surveys performed in 1987 and 1992 (23% and 14%, respectively). By 1997, the percentage of anti-HDV-positive subjects had sharply decreased in the 30 to 50 years age group, whereas it was almost unchanged in subjects over 50 years of age. The highest prevalence of anti-HDV antibodies (11.7%) was found in patients with cirrhosis. This prevalence was as high as 40% in the 1987 study. The circulation of HDV sharply decreased in Italy, by 1.5% per year, from 1987 to 1997. This decrease resulted mainly from the reduction in chronic HDV infections in the young, for whom high morbidity and mortality rates were recorded in the past. The results anticipate the almost complete control of HDV infection in the near future.

                Author and article information

                Hepat Mon
                Hepat Mon
                Hepatitis Monthly
                September 2012
                04 September 2012
                : 12
                : 9
                [1 ]G.F. Ingrassia Department, Section of Hygiene and Public Health, University of Catania, Catania, Italy
                [2 ]Rosario Cunsolo, Vittorio Emanuele Hospital of Catania Health Direction, Catania, Italy
                [3 ]Department of Internal Medicine and Systemic Diseases, University of Catania, Catania, Italy
                [4 ]The Great Senescence Research Center, University of Catania, Ospedale Cannizzao, Catania, Italy
                Author notes
                [* ]Corresponding author: Antonio Mistretta, G.F. Ingrassia Department, Section of Hygiene and Public Health, University of Catania, Via Santa Sofia 87, 95123, Catania, Italy. Tel.: +39-953782182, Fax: +39-953782177, E-mail: anmist@
                Copyright © 2012, Baqiyatallah Research Center for Gastroenterology and Liver Diseases

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Original Article

                Infectious disease & Microbiology

                hepatitis b virus, health personnel, vaccination, vaccines


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