Terapevticheskii arkhivTerapevticheskii arkhivТерапевтический архив0040-36602309-5342LLC Obyedinennaya Redaktsiya31159Editorial articleПередовая статьяReview ArticleCurrent possibilities for treatment for hepatitis C virus-induced cryoglobulinemic vasculitis and B-cell lymphomaСовременные возможности лечения криоглобулинемического васкулита и В-клеточной лимфомы, обусловленных вирусом гепатита СIgnatovaT MИгнатоваТ Мtmignatova@newmail.ruMukhinN AМухинН АУчреждение РАМН "НИИ Ревматологии"ГБОУ ВПО "Первый Московский государственный медицинский университет им. И.М. Сеченова" Минздравсоцразвития России151120128411VOL 84, NO11 (2012)ТОМ 84, №11 (2012)818810042020Copyright ©; 2012, Consilium MedicumCopyright ©; 2012, ООО "Консилиум Медикум"2012Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://ter-arkhiv.ru/0040-3660/article/view/31159

The paper presents a detailed review of the data available in the literature on the treatment of cryoglobulinemic vasculitis and some forms of B-cell non-Hodgkin lymphoma caused by hepatitis C virus. It shows treatment successes associated with the use of current combined antiviral therapy (interferon-α and ribavirin) and its combination with anti-CD20 monoclonal antibodies (rituximab). The combined therapy with rituximab and antiviral drugs allows a radical improvement of prognosis in nearly 50% of patients. Remaining treatment problems and new drug prospects are discussed.

Аннотация. Представлен подробный обзор литературы по проблеме лечения криоглобулинемического васкулита и некоторых форм В-клеточной неходжкинской лимфомы, индуцированных вирусом гепатита С. Показаны успехи в лечении, связанные с применением современной комбинированной противовирусной терапии (препараты интерферона-α и рибавирина) и ее сочетания с CD20 моноклональными антителами (ритуксимабом). Сочетанная терапия ритуксимабом и противовирусными препаратами позволяет радикально улучшить прогноз примерно у 50% больных. Обсуждаются сохраняющиеся трудности в лечении и перспективы, связанные с появлением новых препаратов.

cryoglobulinemic vasculitisB-cell lymphomashepatitis C virusantiviral treatmentrituximabкриоглобулинемический васкулитВ-клеточная лимфомавирус гепатита Спротивовирусное лечениеритуксимабBrouet J.C., Clauvel J.P., Danon F. et al. Biologic and clinical significance of cryoglobulins: a report of 86 cases. Am J Med 1974; 57: 775-788.Ferri C. Mixed cryoglobulinemia. Orphanet J Rare Dis 2008; 3: 25-36.Игнатова Т.М., Серов В.В., Мухин Н.А. и др. HCV-инфекция и смешанная криоглобулинемия. Клин мед 2005; 83: 37-43.Charles E.D., Dustin L.B. Hepatitis C virus-induced cryoglobulinemia. Kidney Int 2009; 76 (8): 818-824.Игнатова Т.М., Апросина З.Г., Серов В.В. и др. Внепеченочные проявления хронического гепатита С. Тер арх 1998; 11: 9-16.Cacoub P., Poynard T., Ghillani P. et al. Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC Group. Multidepartment Virus C. Arthritis Rheum 1999; 42: 2204-2212.Мухин Н.А., Козловская Л.В., Малышко Е.Б. и др. Криоглобулинемический нефрит, ассоциированный с хронической инфекцией вируса гепатита С. Тер арх 2000; 6: 1-5.Игнатова Т.М., Апросина З.Г., Серов В.В. и др. Внепеченочные проявления хронической HCV-инфекции. Рос мед журн 2001; 2: 13-18.Engels E.A., Chatterjee N., Cerhan J.R. et al. Hepatitis C virus infection and non-Hodgkin lymphoma: results of the NCI-SEER multi-center case-control study. Int J Cancer 2004; 111: 76-80.Giordano T.P., Henderson L., Langren O. et al. Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus. JAMA 2007; 297: 2010-2017.Nieters A., Kallinovski B., Brennan P. et al. Hepatitis C and risk of lymphoma: results of European multicenter case-control study EPILYMH. Gastroenterology 2006; 131: 1879-1886.Martyak L.A., Yeganen M., Saab S. Hepatitis C and lymphoproliferative disorders: from mixed cryoglobulinemia to non-Hodgkin's lymphoma. Clin Gastroenterol Hepatol 2009; 7: 900-905.Saadoun D., Landau D.A., Calabrese L.H., Cacoub P. Hepatitis C-associated mixed cryoglobulinemia: a crossroad between autoimmunity and lymphoproliferation. Rheumatology 2007; 46: 1234-1242.Козловская Л.В., Мухин Н.А., Гордовская Н.Б. и др. Факторы риска прогрессирования криоглобулинемического гломерулонефрита, связанного с вирусом гепатита С. Клин мед 2001; 4: 32-35.Ferri C., Marzo E., Longombardo G. et al. Interferon alpha-2b in mixed cryoglobulinemia: a controlled crossover trial. Blood 1993; 81: 1132-1136.Adinolfi L.E., Utili R., Zamprino R. et al. Effects of long-term course of alpha-interferon in patients with chronic hepatitis C associated to mixed cryoglobulinemia. Eur J Gastroenterol Hepatol 1997; 9: 1067-1072.Casato M., Agnello V., Pucillo L.P. et al. Predictors of long-term response to high-dose interferon therapy in type II mixed cryoglobulinemia associated with hepatitis C virus. Blood 1997; 90: 3865-3873.Cresta P., Musset L., Cacoub P. et al. Response to interferon alpha treatment and disappearence of cryoglobulinemia in patients infected by hepatitis C virus. Gut 1999; 45: 122-128.Dammacco F., Sansonno D., Han J.H. et al. Natural interferon-alpha versus its combination with 6-methyl-prednisolone in the therapy of type II mixed cryoglobulinemia: a long-term, randomized, controlled study. Blood 1994; 84: 3336-3343.Mazzaro C., Lacchin T., Moretti M. et al. Effects of two different alpha-interferon regimens on clinical and virological findings in mixed cryoglobulinemia. Clin Exp Rheumatol 1995; 13: Suppl 13, 181-185.Мisiani R., Bellavita P., Fenili D. et al. Interferon alpha-2a therapy in cryoglobulinemia associated with hepatitis C virus. N Engl J Med 1994; 330: 751-756.Naarendorp M., Kallemuchikkal U., Nuovo G.J., Gorevic P.D. Long-term efficacy of interferon-alfa for extrahepatic disease associated with hepatitis C virus infection. J Rheumatol 2001; 28: 2466-2473.Игнатова Т.М., Милованова С.Ю., Мозолевский Ю.В., Апросина З.Г. Успешное лечение интерфероном-альфа и рибавирином криоглобулинемического васкулита, обусловленного HCV-инфекцией. Рос журн гастроэнтерол, гепатол, колопроктол 2004; 2: 64-67.Calleja J.L., Albillos A., Moreno-Otero R. et al. Sustained response to interferon-alfa or to interferon-alfa plus ribavirin in hepatitis C virus associated symptomatic mixed cryoglobulinemia. Aliment Pharmacol Ther 1999; 13: 1179-1186.Zuckerman E., Keren D., Slobodin G. et al. Treatment of refractory, symptomatic, hepatitis C virus related mixed cryoglobulinemia with ribavirin and interferon-alpha. J Rheumatol 2000; 27: 2172-2178.Cacoub P., Lidove O., Maisonobe T. et al. Interferon-a and ribavirin treatment in patients with hepatitis C virus-related systemic vasculitis. Arthr Reumathol 2002; 46: 3317-3326.Mazzaro C., Zorat F., Comar C. et al. Interferon plus ribavirin in patients with hepatitis C virus positive mixed cryoglobulinemia resistant to interferon. J Rheumatol 2003; 30: 1775-1781.Alric L., Plaisier E., Thebault S. et al. Influence of antiviral therapy in hepatitis C virus-associated cryoglobulinemic MPGN. Am J Kidney Dis 2004; 43: 617-623.Cacoub P., Saadoun D., Limal N. et al. PEGylated interferon alfa 2b and ribavirin treatment in patients with hepatititis C virus-related systemic vasculitis. Arthritis Rheum 2005; 52: 911-915.Mazzarro C., Zorat F., Caizzi M. et al. Treatment with peg-interferon alfa-2b and ribavirin of hepatitis C virus-associated mixed cryoglobulinemia: a pilot study. J Hepatol 2005; 42: 632-638.Saadoun D., Reache-Rigon M., Thibault V. et al. Antiviral therapy for hepatitis C virus-associated mixed cryoglobulinemia vasculitis. A long-term follow up study. Arthritis Rheumatism 2006; 54 (11): 3696-3706.Batisse D., Karmochkine M., Jacquot C. et al. Sustained exacerbation of cryoglobulinemia-related vasculitis following treatment of hepatitis C with peginterferon-alfa. Eur J Gastroenterol Hepatol 2004; 16: 701-703.Beuthien W., Mellinghoff H.U., Kempis J.V. Vasculitis complications of interferon-alpha treatment for chronic hepatitis C virus infection: case report and review of the literature. Clin Rheumatol 2005; 30: 369-371.Rossi P., Bertani T., Baio P. et al. Hepatitis C virus-related cryoglobulinemic glomerulonephritis: long-term remission after antiviral therapy. Kidney Int 2003; 63: 2236-2241.Garini G., Allegri L., Iannuzzella F. et al. HCV-related cryoglobulinemic glomerulonephritis: implications of antiviral and immunosuppressive therapies. Acta Biomed 2007; 78: 51-59.Hermine O., Lefrere F., Bronowicki J.P. et al. Regression of splenic lymphoma with villous lymphocynes after treatment of hepatitis C virus infection. N Engl J Med 2002; 347: 89-94.Kelaidi C., Rollot F., Park S. et al. Response to antiviral treatment in hepatitis C virus-ssociated marginal zone lymphomas. Leukemia 2004; 18: 1711-1716.Vallisa D., Bernuzzi P., Arcaini L. et al. Role of anti-hepatitis C virus (HCV) treatment in HCV-related, low-grade, B-cell, non-Hodgkin's lymphoma: a multicenter Italian experience. J Clin Oncol 2005; 23: 468-473.Mazzaro C., De Re V., Spina V. et al. Pegylated-interferon plus ribavirin for HCV-positive indolent non-Hodgkin lymphomas. Br J Hematol 2009; 145 (2): 255-257.Gisbert J.P., Garcia-Buey L., Pajares J.M., Moreno-Otero R. Systematic review: regression of lymphoproliferative disorder after treatment for hepatitis C infection. Aliment Pharmacol Ther 2005; 21: 653-662.Levine J.W., Gota C., Fessler B.J. et al. Persistent cryoglobulinemic vasculitis following successful treatment of hepatitis C virus. J Rheumatol 2005; 32: 1164-1167.Casato M., Lilli D., Donato G. et al. Occult hepatitis C virus infection in type II mixed cryoglobulinemia. J Viral Hepat 2003; 10: 455-499.Quartuccio L., De Marchi G., Fabris M., De Vita S. Development of type II mixed cryoglobulinemic syndrome after effective and persistent hepatitis C virus eradication. Rheumatology 2007; 46 (2): 367-368.Игнатова Т.М., Соловьева О.В., Чернова О.А., Кривошеев О.Г. Эффективное лечение ритуксимабом и противовирусными препаратами язвенно-некротического васкулита тяжелого течения и латентной HCV-инфекции. В кн: Мухин Н.А. (ред.) Инновационные технологии и прогресс терапевтической клиники. Сборник статей. М: Русский врач 2008: 112-116.Landau D.-A., Saadoun D., Halfon P. et al. Relapse of hepatitis C virus-associated mixed cryoglobulinemia vasculitis in patients with sustained viral response. Arthritis Rheumatism 2008; 58 (2): 604-611.Giannini C., Petrarca A., Monti M. et al. Association between persistent lymphatic infection by hepatitis C virus after antiviral treatment and mixed cryoglobulinemia. Blood 2008; 111: 2943-2945.Pham T.N.Q., Michalak T.I. Occult persistence and lymphotropism of hepatitis C virus infection. World J Gastroenterol 2008; 14 (18): 2789-2793.Welker M.-W., Zeuzem S. Occult hepatitis C: how convincing are the current data? Hepatology 2008; 49 (2): 665-675.Halfon P., Bourliere M., Ouzan D. et al. Occult hepatitis C virus infection revisited with ultrasensitive real-time PCR assay. J Clin Microbiol 2008; 46: 2106-2108.Fabris M., Quartuccio L., Sacco S. et al. B-Lymphocyte stimulator (BLyS) up-regulation in mixed cryoglobulinemia syndrome and hepatitis-C virus infection. Rheumatology 2007; 46 (1): 37-43.De Vita S., Quartuccio L., Fabris M. Hepatitis C virus infection, mixed cryoglobulinemia and BLyS upregulation: targeting the infectious trigger, autoimmune response, or both? Autoimmun Rev 2008; 8: 95-99.Насонов Е.Л. Перспективы применения ритуксимаба при аутоиммунных заболеваниях человека. Рус мед журн 2007; 15 (26): 1-6.Sansonno D., De Re V., Lauletta G. et al. Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon-a with an anti-CD20. Blood 2003; 101: 3818-3826.Zaja F., De Vita S., Mazzaro C. et al. Efficacy and safety of rituximab in type II mixed cryoglobulinemia. Blood 2003; 101: 3827-3834.Cacoub P., Delluc A., Saadoun D. et al. Anti-CD20 monoclonal antibody (rituximab) treatment for cryoglobulinemic vaskulitis: where do we stand? Ann Rheum Dis 2008; 67 (3): 283-287.Roccatello D., Baldovino S., Rossi D. et al. Rituximab as a therapeutic tool in severe mixed cryoglobulinemia. Clin Rev Allergy Immunol 2008; 34 (1): 11-117.Wink F., Houtman P.M., Jansen T.L. Rituximab in cryoglobulinemic vasculitis, evidence for its effectivity: a case report and review of literature. Clin Rheumatol 2011; 30 (2): 293-300.Милованова С.Ю., Лопаткина Т.Н., Козловская Л.В., Краснова Т.Н. Моноклональные антитела к В-лимфоцитам (ритуксимаб) в лечении HCV-ассоциированного криоглобулинемического гломерулонефрита. Тер арх 2007; 79 (6): 69-72.Saadoun D., Resche-Rigon M., Sene D. et al. Rituximab combined with Peg-interferon-ribavirin in refractory hepatitis C virus-associated cryoglobulinemia vasculitis. Ann Rheum Dis 2008; 67: 1431-1436.Saadoun D., Resche Rigon M., Sene D. et al. Rituximab plus Peg-interferon-α/ribavirin compared with Peg-interferon-α/ribavirin in hepatitis C-related mixed cryoglobulinemia. Blood 2010; 116 (3): 326-334.Dammacco F., Tucci F.A., Lauletta G. et al. Pegilated interferon-α, ribavirin and rituximab combined therapy of hepatitis Cvirus-related mixed cryoglobulinemia: a long-term study. Blood 2010; 116 (3): 343-353.Monti G., Saccardo F., Rinaldi G. et al. Colchicine in the treatment of mixed cryoglobulinemia. Clin Exp Rheumatol 1995; 13 Suppl 13: S197-199.Hamaguchi M., Kawahito Y., Tsubouchi Y. et al. Combination therapy of prednisolone and mizoribine improves cryoglobulinemic vasculitis with purpura and skin ulcers. Clin Rheumatol 2007; 26 (7): 1170-1172.Ballare M., Bobbio F., Poggi S. et al. A pilot study on the effectiveness of cyclosporine in type II mixed cryoglobulinemia. Clin Exp Rheumatol 1995; 13 Suppl 13: S201-203.Ramos-Casals M., Font J. Mycophenolate mofetil in patients with hepatitis C virus infection. Lupus 2005; 14: 64-72.Oduin J., D'Costa D., Freeth M. et al. Cryoglobulinemic vasculitis caused by intravenous immunoglobulin treatment. Nephrol Dial Transplant 2001; 16: 403-406.Yebra M., BarriosY., Rincon J. et al. Severe cutaneous vasculitis following intravenous infusion of gammaglobulin in patient with type II mixed cryoglobulinemia. Clin Exp Rheumatol 2002; 20: 225-227.Petrarca A., Rigacci L., Caini P. et al. Safety and efficacy of rituximab in patients with hepatitis C virus-related mixed cryoglobulinemia and sever liver disease. Blood 2010; 116 (3): 335-342.