Zusammenfassung
Hintergrund: Bei Patienten mit chronischen Lebererkrankungen sind prophylaktische Impfungen gegen Hepatitis A und B empfohlen.
Methoden: Wir verglichen daher prospektiv die Immunogenität und Reaktogenität des kombinierten Hepatitis-A/B-Impfstoffes (Twinrix®) in einem akzelerierten Impfschema (0-7-21 Tage) mit dem Standardimpfschema (0-1-6 Monate) bei Patienten mit einer chronischen HCV-Infektion und gesunden Kontrollen.
Ergebnisse: Lokale und systemische Nebenwirkungen waren mild bei allen Impflingen. Einen Monat nach Komplettierung des akzelerierten und Standardimpfprotokolls waren 89 bzw. 88 % aller HCV-infizierten Patienten geschützt gegen Hepatitis A (anti-HAV > 33 IU/l), wobei diese Serokonversionsraten auf 94 bzw. 96 % gesteigert werden konnten durch erneute Boosterimmunisierung der initialen Nonresponder. Eine erfolgreiche Anti-HBs-Seroprotektion (Anti-HBs > 10 IU/l) konnte bei 77 und 82 % der HCV-Infizierten nach dem Schnellimpf- bzw. dem Standardimpfschema erzielt werden. Durch Boosterimpfung der initialen Nonresponder konnte die Anti-HBs-Serokonversionsrate sogar auf 84 bzw. 85 % bei Patienten mit einer chronischen HCV-Infektion angehoben werden. Protektive anti-HAV- und anti-HBs-Titer konnten in 89 bzw. 77 % der Fälle bereits zu Monat 2 mit dem Schnellimpfschema bei Hepatitis-C-Infizierten nachgewiesen werden. Gesunde Probanden entwickelten unabhängig vom Impfprotokoll protektive Anti-HAV- und Anti-HBs-Titer in 100 bzw. 98 % der Fälle.
Zusammenfassung: Diese Studie konnte zum ersten Mal zeigen, dass das akzelerierte Impfschema mit dem kombinierten Hepatitis-A/B-Impfstoff sicher und hoch immunogen ist auch in der Problemgruppe der Patienten mit einer chronischen Hepatitis-C-Virusinfektion.
Abstract
Objectives: Hepatitis A (HAV) and B (HBV) vaccinations are recommended in patients with chronic liver diseases.
Methods: We prospectively investigated immunogenicity and safety of an accelerated vaccination protocol (0-7-21 days) with the combined hepatitis A/B vaccine (Twinrix®) versus the standard vaccination scheme (0-1-6 months) in hepatitis C virus-infected patients versus healthy volunteers.
Results: Local and general symptoms were mostly mild in all groups. One month after completion of the accelerated vaccination or standard vaccination, with the combined hepatitis A/B vaccine anti-HAV seroconversion rates (>33 IU/l) were 89 % and 88 % in HCV-infected patients. Initial HCV-nonresponders developed protective anti-HAV antibodies in 94 % and 96 % after a booster dose. According to the anti-HBs seroprotection rate, HCV-infected patients developed protective anti-HBs titres (>10 IU/l) in 77 % and 82 % of cases one month after the accelerated and the standard vaccination scheme-at month 2 and 7, respectively. This anti-HBs seroprotection rate could even be increased to 84 % and 85 % when initial HCV-infected nonresponders where given a booster dose with the combined hepatitis A/B vaccine. Protective anti-HAV and anti-HBs titers were achieved as early as month 2 after the accelerated vaccination schedule in the majority of HCV-infected patients. Healthy subjects developed protective anti-HAV titers and anti-HBs titers in 100 % and 98 % after the accelerated and standard vaccination protocol.
Conclusions: This study is the first to have demonstrated that the accelerated combined hepatitis A/B vaccination is both safe and highly immunogenic against HAV and HBV in HCV-infected patients with well compensated liver disease.
Schlüsselwörter
Hepatitis-A/B-Impfstoff - Hepatitis-C-Virunsinfektion - Schnellimpfschema
Key words
Hepatitis A/B vaccine - hepatitis C virus infection - accelerated vaccination
References
1 Hadler S C. Global impact of hepatitis A virus infection: Changing patterns. Hollinger F, Lemon S, Margolis HS Viral Hepatitis and Liver Disease Baltimore; Williams and Wilkins 1991: 14-20
2 Margolis H S, Hadler S, Shapiro C. et al .Immunization strategies for the control of hepatitis A in the United States. Hollinger F, Lemon S, Margolis HS Viral Hepatitis and Liver Disease Baltimore; Williams and Wilkins 1991: 21-30
3
Keeffe E B.
Is hepatitis A more severe in patients with chronic hepatitis B and other chronic liver diseases?.
Am J Gastroenterol.
1995;
90
201-205
4
Vento S, Garofano T, Renzini C. et al .
Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C.
New Engl J Med.
1998;
338
286-290
5
Koff R S.
Risks associated with hepatitis A and hepatitis B in patients with hepatitis C.
J Clin Gastroenterol.
2001;
331 (1)
20-26
6
Liaw Y F, Yeh C T, Tsai S L.
Impact of acute hepatitis B virus superinfection on chronic hepatitis C virus infection.
Am J Gastroenterol.
2000;
95 (10)
2978-2980
7 Impfempfehlungen der Ständigen Impfkommission (STIKO) am Robert Koch-Institut. Robert Koch Institut Epidemiologisches Bulletin 1998 15: 101-112
8
Lemon S M, Thomas D L.
Vaccines to prevent viral hepatitis.
New Engl J Med.
1997;
336 (3)
196-200
9
Keeffe E B, Iwarson S, McMahon B. et al .
Safety and immunogenicity of hepatitis A vaccine in patients with chronic liver disease.
Hepatology.
1998;
27
881-886
10
Lee S D, Chan C Y, Yu M I. et al .
Safety and immunogenicity of inactivated hepatitis A vaccine in patients with chronic liver disease.
J Med Virol.
1997;
52
215-218
11
Dumot J, Barnes D, Younossi Z. et al .
Immunogenicity of hepatitis A vaccine in decompensated liver disease.
Am J Gastroenterol.
1999;
94
1601-1604
12
Keeffe E B, Krause D S.
Hepatitis B vaccination of patients with chronic liver disease.
Liver Transplant Surg.
1998;
4
437-439
13
Wiedmann M, Liebert U G, Oesen U. et al .
Decreased immunogenicity of recombinant hepatitis B vaccine in chronic hepatitis C.
Hepatology.
2000;
31
230-234
14
Reutter J, Bart P, Francioli P. et al .
Production of antibody to hepatitis A virus and hepatitis B surface antigen measured after combined hepatitis A/hepatitis B vaccination in 242 adult volunteers.
J Viral Hepatol.
1998;
5
205-211
15
Thoelen S, Van Damme P, Leentvaar-Kuypers A. et al .
The first combined vaccine against hepatitis A and B: an overview.
Vaccine.
1999;
17
1657-1662
16
Kallinowski B, Knöll A, Lindner E. et al .
Can monovalent hepatitis A and B vaccines be replaced by a combined hepatitis A/B vaccine during the primary immunization course?.
Vaccine.
2001;
19
16-22
17
Ramonet M, da Silveira T R, Lisker-Melman M. et al .
A two-dose combined vaccine against hepatitis A and hepatitis B in healthy children and adolescents compared to the corresponding monovalent vaccines.
Arch Med Res.
2002;
33
67-73
18
Nothdurft H, Dietrich M, Zuckermann J. et al .
A new accelerated vaccination schedule for rapid protection against hepatitis A and B.
Vaccine.
2002;
20
1157-1162
19
Burbach G, Bienzle U, Stark K. et al .
Influenza vaccination in liver transplant recipients.
Transplantation.
1999;
67
753-755
20
Huzly D, Neifer S, Reinke P. et al .
Routine immunizations in adult renal transplant recipients.
Transplantation.
1997;
63
839-845
21
Fisman D N, Agrawal D, Leder K.
The effect of age on immunologic response to recombinant hepatitis B vaccine: a meta-analysis.
Clin Infect Dis.
2002;
35 (11)
1368-1375
22
De Maria N, Idilman R, Colantoni A. et al .
Increased effective immunogenicity to high dose and short-interval hepatitis B virus vaccination in individuals with chronic hepatitis without cirrhosis.
J Viral Hepat.
2001;
8
372-376
23
Idilman R, De M N, Colantoni A. et al .
The effect of high dose and short interval HBV vaccination in individuals with chronic hepatitis C.
Am J Gastroenterol.
2002;
97 (28)
435-439
24
Leroux-Roels G, Moreau W, Desombere I. et al .
Safety and immunogenicity of a combined hepatitis A and hepatitis B vaccine in young healthy adults.
Scand J Gastroenterol.
1996;
31
1027-1031
25
Avdicova M, Prikazsky V V, Hudeckova H. et al .
Immunogenicity and reactogenicity of a novel hexavalent DTPa-HBV-IPV/HiB vaccine compared to separate comcomitant injections of DTPa-IPV/HiB and HBV vaccines, when administered according to a 3, 5 and 11 month vaccination schedule.
Eur J Pediatr.
2002;
161 (11)
581-587
26
Joines R W, Blatter M, Abraham B. et al .
A prospective, randomized, comparative US trial of a combination hepatitis A and B vaccine (TwinrixTM) with corresponding monovalent vaccines (HavrixTM and Engerix-BTM) in adults.
Vaccine.
2001;
19
4710-4719
27
Bock H L, Löscher T, Scheiermann N. et al .
Accelerated schedule for hepatitis B immunization.
J Travel Med.
1995;
7
213-217
Birgit Kallinowski, MD, PhD
Dept. of Internal Medicine IV, University of Heidelberg
Bergheimer Straße 58
69115 Heidelberg
Germany
Email: birgit_kallinowski@med.uni-heidelberg.de