Criteria for hepatitis B virus screening and validation of blood components in Italy: the position of the SIMTI HBV working group

The screening strategies for the detection of blood donors potentially able to transmit an infection to the recipient of their blood or blood products have always included clinical, behavioural and laboratory criteria in an attempt to construct a "multi-barrier" system that most effectively guarantees transfusion safety1. These criteria are necessarily modified over time as further knowledge is acquired and new laboratory tests become available. Hepatitis B virus (HBV) causes the blood-borne viral infection for which serological markers for screening have been available for the longest time. Indeed, the introduction of a test to detect the hepatitis B surface antigen (HBsAg) at the beginning of the 1970s certainly contributed to a drastic reduction in the number of HBV transfusion-transmitted infections. However, despite continuous improvements in the sensitivity of this test, transfusion-related transmission of hepatitis B has not been completely eliminated and in some countries an additional serological investigation (the search for antibodies against HBV core antigen, anti-HBc) was introduced. Testing for these antibodies was initially used as a "surrogate marker" for the detection of non-A, non-B hepatitis in the mid-1980s, but after the availability of a specific test for hepatitis C virus (HCV), it returned to being of specific relevance in the screening for HBV infection. More recently, a test to detect HBV DNA was introduced for the screening of blood donors. Crucially, this test can detect an acute HBV infection earlier than HBsAg and anti-HBc tests, thus reducing the so called "window period" during which an infected donors may harbour large amounts of infectious viral particles in the absence of serological markers and/or signs and symptoms of an ongoing infection2. Furthermore, DNA testing allows the identification of a number of donors -including periodic donors-characterised by the absence of HBsAg in the presence of HBV DNA with or without anti-HBs, anti-HBc and/or anti-HBe antibodies. These latter serological profiles are defined as "occult HBV infection (OBI)" in agreement with the Consensus Conference held in Taormina in 20083. In these cases, the amount of HBV DNA -when detectable- is usually very low (<100–200 IU/mL). On the basis of the serological profile, OBI can be distinguished into seropositive (anti-HBc and/or anti-HBs positive) or seronegative (anti-HBc and anti-HBs negative) types3. The tests that, at present, are mandatory in Italy for the prevention of transfusion-related transmission of HBV include HBsAg (using several commercially available "last-generation" immunoassays kits) and HBV DNA detection (50% of blood units are tested in pools of 6 samples by Roche Cobas Taqscreen MPX on the Cobas s 201 platform [Roche Instruments Center, Rotkreuz, Switzerland] and 50% in single tests by Novartis Ultrio [Emerville, CA] with comparable analytical and clinical sensitivity4,5). In addition, other serological tests are performed, with a heterogeneous distribution across the country, in part as an additional criterion for the validation of blood components (i.e. anti-HBc) and in part as an evaluation of the immunological status of the donor (i.e. anti-HBs). A national survey organised by the Italian Society of Transfusion Medicine and Immunohaematology (SIMTI) in 20096 found that 78 (43%) of 181 Transfusion Services (TS) that replied to a specific questionnaire routinely performed anti-HBc and that 53 of these 78 (68%) TS were located in Northern Italy Regions. In most of the TS (81%) participating in the study, this test was carried out in first-time donors only, while in the remaining (19%) it was carried out in all donors. Fifty percent of the TS that performed this test used a positive result for anti-HBc as a criterion to exclude antibody-positive donors from donating while the remaining TS did not. Thus, there are profound differences in the behaviour of TS, resulting from the persistence of criteria based on serological parameters and criteria derived from the introduction of the new molecular biology tests. In the light of this, SIMTI set up a Working Group charged with the task of defining the screening tests for HBV capable of guaranteeing the highest levels of safety compatible with the possibility of ensuring timely and appropriate transfusion therapy in the specific Italian epidemiological context, with the currently available technology.