Die infektiöse Hepatitis: extrahepatische Manifestationen und der Einfluss auf die antirheumatische Therapie

Zusammenfassung

Rheumatologische Beschwerden bei gleichzeitig vorliegender Infektion mit dem hepatotropen Hepatitis B (HBV) und Hepatitis C Virus (HCV) stellen häufig ein diagnostisches Dilemma dar, da beide Virusinfektionen neben einer Hepatitis, extrahepatische rheumatoide Manifestationen verursachen können. Beispielsweise ist das Auftreten von Arthralgien, einer Arthritis, einer Vaskulitis, als auch einer Sicca-Symptomatik möglich. Diese sprechen zumeist gut auf eine antivirale Therapie an. Als auslösende Pathomechanismen sind sowohl virusspezifische Faktoren, wie Immunkomplexe oder eine Stimulation von B-Zellen, als auch patientenspezifische Faktoren bekannt. Zugleich schließt eine HBV oder HCV Infektion eine zeitgleiche, nicht virusassoziierte rheumatische Erkrankung nicht aus, deren Diagnostik bei unspezifischer Erhöhung von Autoantikörpern im Rahmen einer HBV oder HCV Infektion häufig erschwert ist. Darüber hinaus stellen vor allem auch moderne antirheumatische Therapien im Falle einer chronischen Virushepatitis ein signifikantes Risiko für eine Reaktivierung bis hin zum fulminanten Leberversagen dar. Im Folgenden gehen wir daher auf häufige extrahepatische Manifestationen der Hepatitis B und C ein, welche eine relevante Differenzialdiagnose für die rheumatologische Praxis darstellen. Zudem werden aktuelle Empfehlungen und Risiken der Anwendung antirheumatischer Therapien bei Patienten mit rheumatologischen Erkrankungen und chronischer HBV oder HCV Infektion diskutiert.

Abstract

Rheumatologic symptoms and concurrent infections with the hepatotropic hepatitis B (HBV) and hepatitis C virus (HCV) often pose a diagnostic dilemma because both viral infections may cause extrahepatic rheumatoid manifestations in addition to hepatitis. For example, arthralgia, arthritis, vasculitis and sicca symptoms may occur, which usually respond well to antiviral therapy. Triggering pathomechanisms include virus-specific factors, e. g. immune complexes or stimulation of B cells, and patient-specific factors. However, a HBV or HCV infection does not rule out a concurrent, non-virus-associated rheumatic disease, which is difficult to diagnose as HBV or HCV infections are often associated with an unspecific elevation of autoantibody levels. Moreover, modern antirheumatic therapies pose a significant risk of reactivation or even fulminant hepatic failure in the case of chronic viral hepatitis. In the following, we will discuss frequent extrahepatic manifestations of HBV and HCV infections, which are a relevant differential diagnosis for rheumatologic practice. In addition, we will discuss current recommendations and risks regarding the use of antirheumatic therapies in patients with rheumatic diseases and chronic HBV or HCV infections.

Schlüsselwörter

Hepatitis B Virus - Hepatitis C Virus - extrahepatische Manifestationen - Reaktivierung - panarteritis nodosa

Key words

HBV - HCV - reactivation - extrahepatic manifestations - panarteritis nodosa

• Literatur

• 1 Trépo C, Chan HLY, Lok A. Hepatitis B virus infection. The Lancet 2014; 384: 2053-2063
• 2 Protzer U, Maini MK, Knolle PA. Living in the liver: Hepatic infections. Nat Rev Immunol 2012; 12: 201-213
• 3 Westbrook RH, Dusheiko G. Natural history of hepatitis C. Journal of Hepatology 2014; 61: S58-S68
• 4 Trépo C, Amiri M, Guillevin L. Extrahepatic manifestations of hepatitis B infection. In Viral Hepatitis. John Wiley & Sons, Ltd;; 2013: 154-162
• 5 Maasoumy B, Manns MP, Cornberg M. Extrahepatic manifestations of hepatitis C virus infection. In Viral Hepatitis. John Wiley & Sons, Ltd;; 2013: 295-309
• 6 Palazzi C, Buskila D, D‘Angelo S. et al. Autoantibodies in patients with chronic hepatitis C virus infection: Pitfalls for the diagnosis of rheumatic diseases. Autoimmun Rev 2012; 11: 659-663
• 7 Vassilopoulos D, Calabrese LH. Management of rheumatic disease with comorbid HBV or HCV infection. Nat Rev Rheumatol 2012; 8: 348-357
• 8 Watanabe R, Ishii T, Kobayashi H. et al. Prevalence of hepatitis B virus infection in patients with rheumatic diseases in Tohoku area: A retrospective multicenter survey. Tohoku J Exp Med 2014; 233: 129-133
• 9 Fattovich G, Olivari N, Pasino M. et al. Long-term outcome of chronic hepatitis B in Caucasian patients: Mortality after 25 years. Gut 2008; 57: 84-90
• 10 McMahon BJ. The natural history of chronic hepatitis B virus infection. Hepatology 2009; 49: S45-S55
• 11 Ott JJ, Stevens GA, Groeger J. et al. Global epidemiology of hepatitis B virus infection: New estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 2012; 30: 2212-2219
• 12 Protzer U, Schaller H. Immune escape by hepatitis B viruses. Virus Genes 2000; 21: 27-37
• 13 Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol 2005; 5: 215-229
• 14 European Association For The Study Of The L. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. Journal of Hepatology 2012; 57: 167-185
• 15 Han SH. Extrahepatic manifestations of chronic hepatitis B. Clin Liver Dis 2004; 8: 403-418
• 16 Neumann HA, Berretty PJ, Folmer SC. et al. Hepatitis B surface antigen deposition in the blood vessel walls of urticarial lesions in acute hepatitis B. The British Journal of Dermatology 1981; 104: 383-388
• 17 Scott DG, Bacon PA, Elliott PJ. et al. Systemic vasculitis in a district general hospital 1972–1980: Clinical and laboratory features, classification and prognosis of 80 cases. Q J Med 1982; 51: 292-311
• 18 McMahon BJ, Bender TR, Templin DW. et al. Vasculitis in Eskimos living in an area hyperendemic for hepatitis B. JAMA: The Journal of the American Medical Association 1980; 244: 2180-2182
• 19 Guillevin L, Mahr A, Callard P. et al. Hepatitis B virus-associated polyarteritis nodosa: Clinical characteristics, outcome, and impact of treatment in 115 patients. Medicine (Baltimore) 2005; 84: 313-322
• 20 Trepo C, Guillevin L. Polyarteritis nodosa and extrahepatic manifestations of HBV infection: The case against autoimmune intervention in pathogenesis. Journal of Autoimmunity 2001; 16: 269-274
• 21 Wartelle-Bladou C, Lafon J, Trépo C. et al. Successful combination therapy of polyarteritis nodosa associated with a pre-core promoter mutant hepatitis B virus infection. Journal of Hepatology 2001; 34: 774-779
• 22 Guillevin L, Jarrousse B, Lok C. et al. Longterm follow-up after treatment of polyarteritis nodosa and Churg-Strauss angiitis with comparison of steroids, plasma exchange and cyclophosphamide to steroids and plasma exchange. A prospective randomized trial of 71 patients. The Cooperative Study Group for Polyarteritis Nodosa. J Rheumatol 1991; 18: 567-574
• 23 Kappus MR, Sterling RK. Extrahepatic manifestations of acute hepatitis B virus infection. Gastroenterol Hepatol (NY) 2013; 9: 123-126
• 24 Combes B, Shorey J, Barrera A. et al. Glomerulonephritis with deposition of Australia antigen-antibody complexes in glomerular basement membrane. Lancet 1971; 2: 234-237
• 25 Chan TM. Hepatitis B and renal disease. Curr Hepat Rep 2010; 9: 99-105
• 26 Gilbert RD, Wiggelinkhuizen J. The clinical course of hepatitis B virus-associated nephropathy. Pediatric Nephrology 1994; 8: 11-14
• 27 Lai KN, Li PK, Lui SF. et al. Membranous nephropathy related to hepatitis B virus in adults. The New England Journal of Medicine 1991; 324: 1457-1463
• 28 Fabrizi F, Dixit V, Martin P. Meta-analysis: Anti-viral therapy of hepatitis B virus-associated glomerulonephritis. Alimentary Pharmacology & Therapeutics 2006; 24: 781-788
• 29 Chung DR, Yang WS, Kim SB. et al. Treatment of hepatitis B virus associated glomerulonephritis with recombinant human alpha interferon. Am J Nephrol 1997; 17: 112-117
• 30 Mazzaro C, Dal Maso L, Urraro T. et al. Hepatitis B virus related cryoglobulinemic vasculitis: A multicentre open label study from the Gruppo Italiano di Studio delle Crioglobulinemie – GISC. Digestive and liver disease: Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2016; 48: 780-784
• 31 Franceschi S, Lise M, Trepo C. et al. Infection with hepatitis B and C viruses and risk of lymphoid malignancies in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer epidemiology, biomarkers & prevention: A publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2011; 20: 208-214
• 32 Hedegaard DL, Tully DC, Rowe IA. et al. High resolution sequencing of hepatitis C virus reveals limited intra-hepatic compartmentalization in end stage liver disease. Journal of Hepatology 2016;
• 33 Thein HH, Yi Q, Dore GJ. et al. Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: A meta-analysis and meta-regression. Hepatology 2008; 48: 418-431
• 34 European Association for Study of L. EASL Recommendations on treatment of hepatitis C 2015. Journal of Hepatology 2015; 63: 199-236
• 35 Zignego AL, Craxi A. Extrahepatic manifestations of hepatitis C virus infection. Clin Liver Dis 2008; 12: 611-636 ix
• 36 Zignego AL, Ferri C, Pileri SA. et al. Extrahepatic manifestations of Hepatitis C Virus infection: A general overview and guidelines for a clinical approach. Digestive and liver disease: Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2007; 39: 2-17
• 37 Ferri C, Ramos-Casals M, Zignego AL. et al. International diagnostic guidelines for patients with HCV-related extrahepatic manifestations. A multidisciplinary expert statement. Autoimmun Rev 2016;
• 38 Cacoub P, Comarmond C, Domont F. et al. Extrahepatic manifestations of chronic hepatitis C virus infection. Ther Adv Infect Dis 2016; 3: 3-14
• 39 Palazzi C, Olivieri I, Cacciatore P. et al. Difficulties in the differential diagnosis between primitive rheumatic diseases and hepatitis C virus-related disorders. Clin Exp Rheumatol 2005; 23: 2-6
• 40 Sene D, Limal N, Cacoub P. Hepatitis C virus-associated extrahepatic manifestations: A review. Metab Brain Dis 2004; 19: 357-381
• 41 Ferri C, Longombardo G, La Civita L. et al. Hepatitis C virus chronic infection as a common cause of mixed cryoglobulinaemia and autoimmune liver disease. Journal of Internal Medicine 1994; 236: 31-36
• 42 Ferri C, Monti M, La Civita L. et al. Hepatitis C virus infection in non-Hodgkin‘s B-cell lymphoma complicating mixed cryoglobulinaemia. Eur J Clin Invest 1994; 24: 781-784
• 43 Sise ME, Bloom AK, Wisocky J. et al. Treatment of hepatitis C virus-associated mixed cryoglobulinemia with direct-acting antiviral agents. Hepatology 2016; 63: 408-417
• 44 Visentini M, Tinelli C, Colantuono S. et al. Efficacy of low-dose rituximab for the treatment of mixed cryoglobulinemia vasculitis: Phase II clinical trial and systematic review. Autoimmun Rev 2015; 14: 889-896
• 45 Dal Maso L, Franceschi S. Hepatitis C virus and risk of lymphoma and other lymphoid neoplasms: A meta-analysis of epidemiologic studies. Cancer epidemiology, biomarkers & prevention: A publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2006; 15: 2078-2085
• 46 Zignego AL, Giannelli F, Marrocchi ME. et al. T(14;18) translocation in chronic hepatitis C virus infection. Hepatology 2000; 31: 474-479
• 47 Li X, Fan XW, Liu W. et al. Risk factors for damaged liver function after chemotherapy in hepatitis B virus carriers with non-Hodgkin lymphoma. Genetics and Molecular Research: GMR 2015; 14: 2647-2653
• 48 Felis-Giemza A, Olesinska M, Swierkocka K. et al. Treatment of rheumatic diseases and hepatitis B virus coinfection. Rheumatol Int 2015; 35: 385-392
• 49 Brunasso AM, Puntoni M, Gulia A. et al. Safety of anti-tumour necrosis factor agents in patients with chronic hepatitis C infection: A systematic review. Rheumatology (Oxford) 2011; 50: 1700-1711
• 50 Ringelhan M, Heikenwalder M, Protzer U. Direct effects of hepatitis B virus-encoded proteins and chronic infection in liver cancer development. Digestive Diseases 2013; 31: 138-151