| Sažetak | Okultna infekcija virusom hepatitisa B (OBI) u davatelja krvi najčešći je uzrok prijenosa virusa hepatitisa B (HBV) transfuzijama krvnih pripravaka. OBI se definira kao prisutnost virusne DNA bez prisustva HBsAg-a u krvi izvan tzv. window perioda infekcije. HBV DNA može se dokazati u jetri, a u krvi je uglavnom nedokaziva ili intermitentna jer je virusni titar nizak, najčešće manji od 100, često i od 10 IU HBV DNA/mL. Kod OBI-ja nisu nužno prisutna specifična protutijela na virusne antigene, međutim ako jesu (seropozitivni OBI), najčešće su prisutna protutijela na sržni antigen, anti-HBc. Obzirom na negativan rezultat HBsAg-a i intermitentnu viremiju, prisutna anti-HBc jedini su biljeg koji može upućivati na OBI.
Glavni cilj i svrha ovog istraživanja bio je odrediti prevalenciju anti-HBc-a u populaciji dobrovoljnih davatelja krvi (DDK) Hrvatskog zavoda za transfuzijsku medicinu (HZTM), ukupnu te prema dobi, spolu i broju davanja krvi DDK-a, utvrditi važnost određivanja anti-HBc-a u detekciji OBI-ja, prevalenciju OBI-ja u populaciji DDK-a i procjeniti rizik od prijenosa HBV transfuzijama krvi uključujući DDK-e s OBI-jem. U tom smislu ispitana je prisutnost anti-HBc-a i protutijela na druge antigene HBV-a te virusne DNA u arhivskim uzorcima krvi DDK HZTM-a iz 2004. (7561 uzoraka) i 2013. godine (7318 uzoraka) te prospektivno u 2017. godini (5090 uzoraka).
Zabilježen je značajan pada prevalencije anti-HBc-a u populaciji DDK-a HZTM-a, i to 4 puta, s 5,24 % na 1,32 %, što je uglavnom posljedica pada prevalencije u višestrukih davatelja krvi s 5,90 % na 1,38 %. Serološki HBV profiIi anti-HBc pozitivnih DDK-a nisu se značajno promijenili u ispitivanom periodu: udjeli anti-HBs-a, anti-HBe-a i anti-HBc-only pozitivnih DDK-a bili su podjednaki su sve tri ispitne godine. Nije bilo HBeAg niti anti-HBc IgM pozitivnih DDK-a. Srednja izračunata avidnost anti-HBc IgG-a je 0,92 što upućuje na davni kontakt s HBV-om. Prevalencija anti-HBc-a u populaciji DDK HZTM-a od 1:19 u 2013. i 1:76 u 2017. godini, značajno je viša od prevalencije DDK-a s OBI-jem, koja je 2013. bila 1:11.213, a 2017. godine 1:30.932. Ostatni rizik za 2004. godinu iznosi 1:14.925; za 2013. godinu 1:11.363; za 2017. godinu 1:83.333. Ostatni rizik ima silazni trend. Eliminacijom svih anti-HBc pozitivnih trebalo bi nadoknaditi minimalno 1,32 % DDK-a.
Rad predstavlja originalni znanstveni doprinos u potvrdi važnosti anti-HBc testa u otkrivanju DDK-a s mogućim OBI-jem, u slučajevima intermitentne HBV DNA viremije, te u odabiru strategije ispitivanja DDK-a na anti-HBc, uz postojeći panel HBsAg i ID-NAT (od engl. Individual Donor-Nucleic Acid Testing) u Republici Hrvatskoj, što bi bila dodatna mjera u spriječavanju prijenosa HBV-a krvlju i krvnim pripravcima. |
| Sažetak (engleski) | Occult hepatitis B virus infection (OBI) in blood donors (BDs) is the most common cause of transmission of hepatitis B (HBV) by blood products. OBI is defined as the presence of HBV DNA with no detectable surface antigen, HBsAg, in blood, excluding the window period, with or without any specific HBV antibodies, and if the antibodies are present (seropositive OBI), they are mostly specific antibodies to the core antigen, anti-HBc. The efficiency of anti-HBc tests is sometimes greater than the efficiency of NAT (Nucleic Acid Testing) tests, in cases of very low HBV DNA viral load, which approximately corresponds to the lower limit of sensitivity of the NAT method. Those are mostly donors with less than HBV DNA 10 IU/mL of blood.
The objective of the proposed doctoral thesis was to determine the seroprevalence of anti-HBc, the importance of determining anti-HBc in OBI, the prevalence of OBI among BDs and to evaluate the risk of transmission of HBV including BDs with OBI. For this purpose archived samples of BDs of the Croatian Institute of Transfusion Medicine (CITM) from 2004 (7561) and 2013 (7318) and prospectively in 2017 (5090) were analyzed for the presence of anti-HBc and other HBV antibodies and viral DNA.
During the period 2004-2017, a significant 4-times decrease in anti-HBc prevalence in Croatian BDs from 5.24 % to 1.32 % was observed. Serological HBV profiles of anti-HBc positive BDs did not change significantly during the study period: the shares of anti-HBs, anti-HBe, and anti-HBc-only positive BDs were equal in all three testing years. There was no HBeAg or anti-HBc IgM positive BDs. The mean calculated avidity of anti-HBc IgG is 0.92 which indicates long-standing contact with HBV. The prevalence of anti-HBc in the population of BDs in the CITM was 1:19 in 2013 and 1:76 in 2017 and is significantly higher than the prevalence of OBI BDs, which was 1:11.213 in 2013 and 2017 1:30.932. The residual risk for 2004 is 1:14.925; for 2013 1:11.363; for 2017 1:83.333. The residual risk has a decline trend. No OBI infection among anti-HBc positive BDs was detected in this study. By deferring all anti-HBc positive donors, at least 1.32 % of BDs should be substituted.
The results of this work present original scientific contribution about the anti-HBc seroprevalence in BDs, the incidence of OBI BDs and risk of transmission of HBV including blood products from OBI donors. Due to the high consistency of anti-HBc in Croatian OBI BDs, a strategy of universal testing of BDs for this marker in addition to existing HBsAg and ID-NAT screening in Croatia would represent an additional measure to prevent HBV transmission by blood and blood components. |
