Ochorenie na vírusovú hepatitídu B po kompletnom očkovaní

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1 Ochorenie na vírusovú hepatitídu B po kompletnom očkovaní Hudáčková D., Urbančíková I. Centrum na očkovanie detí s komplikáciami a kontraindikáciami očkovania Detské infekčné oddelenie Detská fakultná nemocnica Košice VIII. Hradecké vakcinologické dny,

2 Anamnéza: 15- ročný chlapec RA: matka zomrela na rakovinu, bližšie neudané, 8 súrodenci zdraví EA: kontakt s infekčným ochorením neudaný, 4 roky je umiestnený v DD, cez letné prázdniny bol doma u otca neodborná aplikácia náušnice Terajšie ochorenie: ikterické skléry biliribín celkový 128,7 mmol/l AST 29,9 ALT 43,9 ukat/l subj. bez ťažkostí, stolica a močenie v norme Prijatý s dg. Hepatitis susp.

3 Stav pri prijatí: TT: 36,7 C TK 116/70 Koža ikterická, bez patolog. eflor., skléry ikterické Brucho v niveau, priehmatné, bez palp.citlivosti, bez patol. rezistencie, hepar H+2cm, lien nehm. USG pečene,žlčníka,pank.,sl.,lymf.uzlín Pečeň je ľahko zväčšená v MCL čiare 157 mm, povrch je hladký, okraj oblý, echogenita je primeraná, jemná cievna kresba je redukovaná, v portae nedilatovaná, tok so zachovalým smerom rýchlosť 29 cm/s. Žlčník je kontrahovaný a epigastrium je tienené. Slezina ľahko zväčšená 127 mm. Obličky bilat primeranej veľkosti i echogenity, bez poruchy odtoku moča. Ľahká hepatosplenomegália.

4 umol/l Hodnoty bilirubínu deň bil. celk. 322,2 bil. konj. 303,3 bilirubín celkový bilirubín konjugovaný 25. deň prepustený domov bil.celk. 76,7 bil. konj. 66,0 51. deň bil. celk. 15,7 bil. konj. 12,7

5 ukat/l Hodnoty aminotransferáz deň AST 42,4 ALT 36, deň prepustený domov AST 3,4 ALT 3, AST ALT 51. deň AST 0,9 ALT 1,1

6 Sérologické vyšetrenia: Anti-HAV IgM... Negat. Anti-HAV IgG... Pozit. postexpozičná profylaxia Anti-HCV... Negat.

7 pacient HBeAg negat. antihbe pozit. HBsAg pozit. anti HBs negat. anti-hbc IgM pozit. anti HBc IgG pozit.

8 Imunizácia proti VHB: 1. po narodení v odstupe 1 mesiaca v odstupe 5 mesiacov

9 Diskusia? non - responder? % netvorí protektívnu protilátkovú odpoveď 1,2 - miesto podania vakcíny, vek, hmotnosť, pohlavie, imunosupresia, imunodeficiencia, fajčenie, HLA haplotypy 3 1 Zuckerman JN. Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccine. J Med Virol 2006;78(2): Jafarzadeh A et al. Differential immunogenicity of a recombinant hepatitis B vaccine in Iranian neonates. Iran J Immunol. 2004;1(2): Zuckerman JN. Immune response to a new hepatitis B vaccine in healthcare workers. BMJ 1997;314:329.

10 Diskusia? non - responder? Zvýšenie imunitnej odpovede: - viacdávkové schémy, vyššie dávky, spôsob podania (intraderm.), zrýchlená schéma - nové adjuvanciá (MPL, MF59) - integrácia PreS1, PreS2 antigénov vakcíny III. generácie - DNA vakcíny Jafarzadeh et al.vaccine 2008;26, Madalinski K. Recent advances in Hepatitis B vaccination. Hep B Annual 2008 ;5:51-65.

11 Diskusia? oslabenie vakcínou indukovanej imunity? - koncentrácia protilátok sa postupne znižuje (rýchly pokles počas 12 mesiacov po vakcinácii) - rýchla anamnestická odpoveď po boostri - Boot JH. (2009) - akútna hepatitída B (genotyp A) 14 rokov po vakcinácii 5 dávkami Zuckerman JN. Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccine. J Med Virol 2006;78(2): Zanneti AR et al. Hot topics in viral hepatitis 2007;5:7-12. Boot JH et al. Acute hepatitis B in a healthcare worker: A case report of genuine vaccination failure. J Hepatol 2009;50:

12 Diskusia? iný zriedkavý genotyp vírusu? - rekombinovaná vakcína obsahuje HBsAg proteíny genotypu A,D - predpokladá sa cross-protektivita 4 - non-a/d genotypy genotyp F 1,3, E 2 1 Tacke, F. Acute hepatitis B virus infection by genotype F despite successful vaccination in an immune-competent German patient. J Clin Virol 2007;38: Mathet VL et al. Detection of hepatitis virus genotype E. J Clin Microbiol 2006, 44(9): O Halloran JA et al. Journal of Clinical Virology 2011;52: Singh AE et al. Journal of Viral Hepatitits 2011;18:

13 Diskusia? genetické variácie vírusu? Mutácie HBV: - mutácie v a determinante - imunitný alebo diagnostický únik - zlyhanie postnatálnej imunoprofylaxie 1 - imunologický selekčný tlak - vakcína, HBIG - prirodzená infekcia - vplyv - vek (dĺžka infekcie), stupeň ochorenia 2 - liečba chronickej hepatitídy B 3,4 1 Hsu HY et al. Hepatology 1997;26: Komatsu et al. BMC Research Notes 2012, 5:22 3 Clements CJ. Global control of hepatitis B virus. Bulletin of the World Health Organization 2010;88: Sheldon J., Soriano V. Hepatitis B virus escape mutants induced by antiviral therapy. J. Antimicrob. Chemother. 2008;61(4):

14 Priebeh ochorenia hospitalizácia AST 0,9 ALT 1,1 HBV DNA 64 ME/ml 345 kópií/ml AST, ALT v norme HBV DNA <20 ME/ml <116 kópií/ml HBsAg negat., HBeAg negat. antihbs 850,8 IU/l (<9,9)

15 Diskusia? priaznivý vplyv očkovania? -breakthrough infection (antihbc, HBV DNA) -dobrý klinický priebeh - parciálna ochrana? - antihbs protilátky klesajúca tendencia, ale imunitná pamäť Scott M. et al. Direct Ex Vivo Evaluation of Long-Lived Protective Antiviral Memory B Cell Responses against Hepatitis B Virus 30, Obr. Barraclough KA, Playford EG. Hepatitis B virus infection in hemodialysis populations: progress toward prevention Kidney International 77, 2010.

16 Ďakujem za pozornosť

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