Aktuelle Rheumatologie 2014; 39(03): 182-185
DOI: 10.1055/s-0033-1363974
Übersichtsarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Hepatologische Aspekte der immunsuppressiven Therapie rheumatologischer Erkrankungen

Hepatological Aspects of Immunosuppressive Therapy for Rheumatic Diseases
W.-J. Mayet
1   Zentrum für Innere Medizin, Nordwest-Krankenhaus Sanderbusch GmbH, Sande, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
20 January 2014 (online)

Zusammenfassung

Immunsuppressive Konzepte stellen die Basis der modernen Therapie entzündlich rheumatischer Erkrankungen dar. Trotz stetig verbesserter Verträglichkeit der Medikamente ist eine planmäßige Kontrolle der Patienten erforderlich, da mit Nebenwirkungen zu rechnen ist. Besonders zu beachten ist dabei die komplexe Beziehung zwischen der Leber und rheumatischen Erkrankungen. So können z. B. im Verlauf eines SLE durch die Beteiligung des hepatischen Gefäßsystems schwere Leberschäden entstehen. Die autoimmune Hepatitis, die primäre biliäre Zirrhose und die primär sklerosierende Cholangitis sind ebenfalls mit rheumatologischen Erkrankungen assoziiert. NSAR verursachen sehr häufig hepatotoxische Effekte. Leiden die Patienten an einer Virushepatitis, kann der Einsatz von klassischen DMARD incl. Biologicals kontraindiziert sein. Dies gilt besonders für Rituximab. Ohne vorherige effektive antivirale Therapie ist die Gefahr einer Reaktivierung unter Immunsuppression sehr hoch.

Abstract

Immunosuppressive concepts are the basis of the modern therapy for inflammatory rheumatic diseases. Despite steadily improved tolerability of the drugs a scheduled supervision of patients is necessary, as side-effects are to be expected. Particular attention must be paid to the complex relationship between the liver and rheumatic diseases. For instance, in the course of systemic lupus erythematosus (SLE) severe liver damage can occur through the involvement of the hepatic vascular system. Autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis are also associated with rheumatic diseases. NSAIDs very frequently cause hepatotoxic effects. For patients suffering from a viral hepatitis, the use of classic DMARDs including biologics can be contraindicated. This particularly applies for Rituximab. Without a preceding effective antiviral therapy the danger of reactivation during immunosuppression is very high.

 
  • Literatur

  • 1 Cantor H, Dumont A. Hepatic suppression of sensitization to antigen absorbed into the portal system. Nature 1969; 223: 472-476
  • 2 Wiegard C, Lohse AW. Leber und Rheuma. Z Rheumatol 2005; 64: 26-31
  • 3 Milan-Mon A, Porto JL, Novo C. Hepatic infarction in a pregnant patient with the primary anti-phospholipid syndrome. Lupus 1993; 2: 275
  • 4 Wanless I, Goldwin TA, Allen F et al. Nodular regenerative hyperplasia of the liver in hematologic disorders: a possible response to obliterative portal venopathy. Medicine 1980; 59: 367
  • 5 Van Hoek B. The spectrum of liver disease in systemic lupus erythematosus. Nether J Med 1996; 46: 244-253
  • 6 Iwai M, Harada Y, Ishii M et al. Autoimmune hepatitis in a patient with systemic lupus erythematosus. Clin Rheumatol 2003; 22: 234-236
  • 7 Kadar J, Petrovicz E. Adult-onset Stills disease. Best Pract Clin Rheumatol 2004; 18: 663-676
  • 8 Weiler-Normann C, Lohse AW. Autoimmune hepatitis: a life-long disease. J Hepatol 2013; 58: 5-7
  • 9 Czaja A. Diverse manifestations and evolving treatments of autoimmune hepatitis. Minerva Gastroenterol Dietol 2005; 51: 313-333
  • 10 Abraham S, Begum S, Isenberg D. Hepatic manifestations of autoimmune rheumatic diseases. Ann Rheum Dis 2004; 63: 123-129
  • 11 Mayet W, Lohse AW. Komorbidität rheumatologischer und hepatologischer Erkrankungen. Z Rheumatol 2013; 72: 547-554
  • 12 Tsianos E, Hoofnagle JH, Foc CPH. Sjögrens syndrome in patients with primary biliary cirrhosis. Hepatology 1989; 11: 730
  • 13 Gow P, Flemming KA, Chapman RW. Primary sclerosing cholangitis associated with rheumatoid arthritis and HLA DR4: is the association a marker of patients with progressive liver disease?. J Hepatol 2001; 34: 631-635
  • 14 Ashwell J, Lu FW, Vacchio MS. Glucocorticoids in T cell development and function. Annu Rev Immunol 2000; 18: 309-345
  • 15 Tur-Kaspa R, Burk RD, Shaul Y et al. Hepatitis B virus DNA contains a glucocorticoid-responsive element. Proc Natl Acad Sci USA 1986; 83: 1627-1631
  • 16 Liaw Y. Hepatitis viruses under immunosuppressive agents. J Gastroenterol Hepatol 1998; 1998: 14-20
  • 17 Manzano-Alonso M, Castellano-Tortajada G. Reactivation of hepatitis B virus infection after cytotoxic chemotherapy or immunosuppressive therapy. World J Gastroenterol 2011; 17: 1531-1537
  • 18 Jobanputra P, Amarasena R, Maggs F. Hepatotoxicity associated with sulfasalazine in inflammatory arthritis. BMC Musculoskel Dis 2008; 9: 48
  • 19 Quintin E, Scoazec JY, Marotte H et al. Rare incidence of methotrexate-specific lesions in liver biopsy of patients with arthritis and elevated liver enzymes. Arthritis Res Ther 2010; 12: R143
  • 20 Keyßer G. Methotrexat-Toxizität Mythen und Fakten. Z Rheumatol 2011; 70: 108-113
  • 21 Saag K, Teng GG, Patkar NM et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008; 59: 762-784
  • 22 Berends MA, Snoek J, de Jong EM et al. Biochemical and biophysical assessment of MTX-induced liver fibrosis in psoriasis patients: Fibrotest predicts the presence and Fibroscan predicts the absence of significant liver fibrosis. Liver International 2007; 27: 639-645
  • 23 Vassilopoulos D, Calabrese LH. Risks of immunosuppressive therapies including biologic agents in patients with rheumatic diseases and co-existing chronic viral infections. Curr Opin Rheumatol 2007; 19: 619-625
  • 24 Roll P, Rubbert-Roth A, Tony HP et al. Tocilizumab.. Z Rheumatol 2010; 69: 608-617
  • 25 Kusumoto S, Tanaka Y, Mizokami M et al. Reactivation of hepatitis B virus following systemic chemotherapy for malignant lymphoma. Int J Hematol 2009; 90: 13-23
  • 26 Kusumoto S, Tanaka Y, Ueda R et al. Reactivation of hepatitis B virus following rituximab-plus-steroid combination chemotherapy. J Gastroenterol Hepatol 2011; 46: 9-16
  • 27 Kremer J, Koff R. A debate: should patients with rheumatoid arthritis on methotrexate undergo liver biopsie?. Semin Arthritis Rheum 1992; 2003: 376
  • 28 Seckin D, Durusoy C, Sahin S. Concomitant vitiligo and psoriasis in a patient with interferon alfa-2a for chronic hepatitis B infection. Pediatr Dermatol 2004; 21: 577-579