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DOI: 10.1055/s-2003-39327
Schwere Exazerbation einer chronischen Hepatitis B unter Therapie mit Kortikosteroiden und Lamivudin und erfolgreiche Kurzzeit-Kombinationstherapie mit Interferon-β und -γ
Severe Exacerbation of Chronic Hepatitis B During Therapy with Corticosteroids and Lamivudine Therapy and Successful Short-term Combination Therapy with Interferon-β and Interferon-γPublication History
Manuskript-Eingang: 4.6.2002
Annahme nach Revision: 5.2.2003
Publication Date:
28 May 2003 (online)

Zusammenfassung
Wegen eines akuten Schubes einer undifferenzierten KoIIagenose/Autoimmunkrankheit mit Gelenkbeschwerden wurde eine 50-jährige Patientin mit langjährig bekannter chronischer Hepatitis B oral mit Kortikosteroiden behandelt (30 mg Prednisolon in absteigender Dosierung für 6 Monate). Darunter kam es zu einer Exazerbation der Hepatitis B und massivem Flare-up unter gleichzeitiger Behandlung mit Lamivudin (GOT 530 U/l, GPT 791 U/l). Die Serologie zeigte Positivität für HBs-Ag und Anti-HBc-lgM sowie eine HBV-DNA mit > 400 000 Kopien/ml in der Polymerasekettenreaktion. Unter Berücksichtigung des höheren Risikos der Reaktivierung von Autoimmunphänomenen unter einer 6-monatigen Therapie mit Interferon-α erfolgte 5 Wochen lang die intensivierte Kombinationstherapie aus Interferon-β und -γ (2 Wochen: 1 × 3 Mill. E nIFN-β Fiblaferon® i. v.; 3 Wochen: 1 × 3 Mill. E nIFN-β i. v. plus 1 × 50 μg rIFN-γ Imukine®) mit kompletter viraler und biochemischer Response nach 2 Monaten. Dieses Ergebnis bestand über einen Beobachtungszeitraum von mindestens 12 Monaten ohne Reaktivierung der Autoimmunkrankheit.
Abstract
Following an acute episode of undifferentiated collagenosis/autoimmune disease with joint pain, a 50-year-old female patient with known long-standing chronic hepatitis B was treated orally with corticosteroids (30 mg prednisolone in decreasing doses over a period of six months). During this treatment, exacerbation of hepatitis B and massive flare-up under simultaneous treatment with lamivudine occurred (GOT 530 U/L, GPT 791 U/L). Serology was positive for HBs-Ag and anti-HBc-lgM. HBV-DNA titer was > 400,000 copies/ml in polymerase chain reaction. Considering the increased risk of reactivation of autoimmune phenomena during a six months therapy with interferon-α, an intensive combination therapy with interferon-β and -γ (2 weeks: 1×3 MIU nIFN-β Fiblaferon® i. v.; 3 weeks: 1×3 MIU nIFN-β i. v. plus 1×50 μg rIFN-γ Imukine®) was carried out over five weeks. After two months this resulted in a complete viral and biochemical response. During an observation period of twelve months no reactivation of the autoimmune disease occurred.
Schlüsselwörter
Hepatitis B - Kortikosteroide - Lamivudin - Autoimmunkrankheit - Interferon-β - Interferon-γ
Key words
Hepatitis B - corticosteroids - lamivudine - autoimmune disease - interferon-β - interferon-γ
Literatur
- 1 Fattovich G, Giustina G, Schalm S W. et al . Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. Hepatology. 1995; 21 77-82
- 2 Sjogren M, Hoofnagle J H. Immunoglobulin A antibody to hepatitis B core antigen in patients with chronic type B hepatitis. Gastroenterol. 1985; 89 252-258
- 3 Pape G R, Rieber E P, Eisenburg J. et al . Involvement of the cytotoxic suppressor T-Cell subset in liver tissue injury of patients with acute and chronic liver disease. Gastroenterol. 1983; 85 657-662
- 4 Perrillo R P. Acute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease. Gastroenterology. 2001; 120 1009-1022
- 5 Nakanishi K, Ishikawa M, Nakauchi M. et al . Antibody to hepatitis B e positive hepatitis induced by withdrawal of steroid therapy for polymyositis: response to interferon-alpha and cyclosporin A. Intern Med. 1998; 37 519-522
- 6 Nojima T, Hirakat M, Sato S. et al . A case of polymyositis associated with hepatitis B infection. Clin Exp Rheumatol. 2000; 18 86-88
- 7 Shiota G, Harada K, Oyama K. et al . Severe exacerbation of hepatitis after short-term corticosteroid therapy in a patient with „latent” chronic hepatitis B. Liver. 2000; 20 415-420
- 8 Koga Y, Kumashiro R, Yasumoto K. et al . Two fatal cases of hepatitis B virus carriers after corticosteroidtherapy for bronchial asthma. Intern Med. 1992; 31 208-213
- 9 Inadomi T, Saito T, Kaneko M. et al . Bullous pemphigoid in an HB virus carrier: interaction between corticosteroids and HB virus. J Dermatol. 1997; 14 179-183
- 10 Hammond A, Ramersdorfer C, Palitzsch K D. et al . Letales Leberversagen nach Corticosteroidtherapie bei Hepatitis-B-Carrier-Status. Dtsch Med Wschr. 1999; 124 687-690
- 11 Markovic S, Drozina G, Vovk M. et al . Reactivation of hepatitis B but not hepatitis C in patients with malignant lymphoma and immunosuppressive therapy. A prospective study in 305 patients. Hepatogastroenterology. 1999; 46 2925-2930
- 12 Lai C L, Chien R N, Leung N WY. et al . A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. N Engl J Med. 1998; 339 61-68
- 13 Malaguarnera M, Restuccia S, Ferlito L. et al . Antiviral drugs in chronic hepatitis B: review and meta-analysis. Int J Clin Pharmacol Ther. 2001; 39 4-11
- 14 Dumoulin F L, Leifeld L, Sauerbruch T. et al . Autoimmunity induced by interferon-alpha therapy for chronic viral hepatitis. Biomed Pharmacother. 1999; 53 242-254
- 15 Caselmann W H, Eisenburg J, Hofschneider P H. et al . β- and γ-interferon in chronic active hepatitis B. A pilot trial of short term combination therapy. Gastroenterol. 1989; 96 449-455
- 16 Musch E, Högemann B, Gerritzen A. et al . Phase II clinical trial of combined natural interferon-β plus recombinant interferon-γ treatment of chronic hepatitis B. Hepato-Gastroenterol. 1998; 45 2282-2294
- 17 Fleischmann W R, Georgiades J A, Osborne L C. et al . Potentiation of interferon activity by mixed preparations of fibroblast and immune interferon. Infect Immun. 1979; 10 248-253
- 18 Rockey D C, Maher J J, Jarnagin W R. et al . Inhibition of rat hepatic lipocyte activation in culture by interferon-gamma. Hepatol. 1992; 16 776-784
- 19 Guido M, Rugge M, Chemello L. et al . Liver stellate cells in chronic viral hepatitis: the effect of interferon therapy. J Hepatol. 1996; 24 301-307
Prof. Dr. med. Dipl.-Biochem. Eugen Musch
Abteilung Allgemeine Innere Medizin, Marienhospital Bottrop
Josef-Albers-Str. 70
46236 Bottrop