Хронический вирусный гепатит В и ревматические болезни: современный взгляд на проблему

Инфекция вызванная вирусом гепатита В (HBV), относится к ряду наиболее распространенных гемоконтактных инфекций. Особый жизненный цикл вируса гепатита В, течение инфекции, часто скрытое, высокий риск развития жизнеугрожающих состояний, таких как фульминантный гепатит и гепатоцеллюлярная карцинома, заставляют проявлять особую осторожность при выборе лечебной тактики в отношении больных ревматологического профиля, поскольку подавляющее большинство используемых в ревматологической практике препаратов обладают иммунодепрессивными свойствами. В настоящем обзоре обновлена информация о рисках реактивации HBVинфекции при лечении применяющимися в настоящее время антиревматическими препаратами, рассмотрены сложные для курации варианты хронического гепатита В с дельта-агентом и внепеченочными проявлениями, в частности, тромбоцитопенией. Наиболее систематизированный и последовательный подход к ранжированию риска реактивации HBV-инфекции (низкий [менее 1 %], умеренный [1–10 %] и высокий [более 10 %]) в соответствии с серологическим статусом пациента, а также типом и продолжительностью используемого иммуносупрессивного лечения предложен Американской гастроэнтерологической ассоциацией. Авторами предпринята попытка унифицировать актуальные литературные данные согласно этой классификации.

1. Ивашкин В. Т., Ющук Н. Д., Маевская М. В. и др.Клинические рекомендации Российской гастроэнтерологической ассоциации и Российского общества по изучению печени по диагностике и лечению взрослых больных гепатитом В. Российский журнал гастроэнтерологии, гепатологии, колопроктологии, 2014; 3: 58–88.

2. Polaris Observatory Collaborators. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: A modelling study. Lancet Gastroenterol Hepatol. 2018 Jun; 3 (6): 383–403. DOI: 10.1016/S 2468–1253(18)30056–6.

3. Гепатит В. Информационный бюллетень ВОЗ от 9 июля 2021 г. Доступно на сайте: https://www.who.int/ru/news-room/fact-sheets/detail/hepatitis-b

4. WHO Publication. Hepatitis B vaccines: WHO position paper – recommendations. Vaccine. 2010; 28 (3): 589–90. DOI: 10.1016/j.vaccine.2009.10.110.

5. Locarnini S. Molecular virology of hepatitis B virus. Semin Liver Dis. 2004; 24 Suppl 1: 3–10. DOI: 10.1055/s-2004–828672.

6. Biondo MI, Germano V, Pietrosanti M, et al. Lack of hepatitis B virus reactivation after anti-tumor necrosis factor treatment in potential occult carriers with chronic inflammatory arthropathies. Eur J Intern Med. 2014; 25 (5): 482–484. DOI: 10.1016/j.ejim.2013.11.014.

7. National Institute for Health and Care Excellence (NICE). Hepatitis B (chronic): diagnosis and management of chronic hepatitis B in children, young people and adults [Internet]. London: NICE; 2013. Available at: http://www.nice.org.uk/guidance/cg165/resources/guidance-hepatitis-bchronic-pdf

8. Инфекционные болезни: национальное руководство. Под ред. Н. Д. Ющука, Ю. Я. Венгерова. 2-е изд., перераб. и доп. М.: ГЭОТАР-Медиа, 2019.

9. European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2017; 67 (2): 370–398. DOI: 10.1016/j.jhep.2017.03.021.

10. Чуланов В. П. Эпидемиологическое и клиническое значение генетической гетерогенности вирусов гепатита А и В: Автореф. дисс. … д-ра мед. наук. Москва, 2013. 47 с.

11. Rizzetto M. Hepatitis D: thirty years after. J Hepatol. 2009; 50 (5): 1043–50. DOI: 10.1016/j.jhep.2009.01.004.

12. Исаева О. В., Кюрегян К. К. Вирусный гепатит дельта: недооцененная угроза. Инфекционные болезни: новости, мнения, обучение. 2019; 8 (2): 72–79. DOI: 10.24411/2305–3496–2019–12010.

13. Servant-Delmas A, Le Gal F., Gallian P., et al. Increasing prevalence of HDV/ HBV infection over 15 years in France. J Clin Virol. 2014; 59 (2): 126–128. DOI: 10.1016/j.jcv.2013.11.016.

14. Obermayer-Straub P, Manns MP. Hepatitis C and D, retroviruses and autoimmune manifestations. J Autoimmun. 2001; 16 (3): 275–85. DOI: 10.1006/jaut.2000.0488.

15. Rehermann B, Lau D, Hoofnagle JH, Chisari FV. Cytotoxic T lymphocyte responsiveness after resolution of chronic hepatitis B virus infection. J Clin Invest. 1996; 97: 1655–1665.

16. Белов БС, Абдурахманов ДТ. Вирус гепатита В и ревматические болезни. Научно-практическая ревматология. 2020; 58 (2): 207–213. DOI: 10.14412/1995–4484–2020–207–213.

17. Jia Y, Zhang J, Mo L et al. Low positivity rates for HBeAg and HBV DNA in rheumatoid arthritis patients: a case-control study. BMC Infect Dis. 2022; 22 (1): 570. DOI: 10.1186/s12879–022–07536–7.

18. Koutsianas C, Hadziyannis E, Thomas K, et al. Kinetics of quantitative hepatitis B surface antigen in patients with rheumatic disease and chronic hepatitis B receiving biologic agents. J Viral Hepat. 2021; 28 (12): 1710–1718. DOI: 10.1111/jvh.13610.

19. Pollicino T, Raffa G, Costantino L, et al. Molecular and functional analysis of occult hepatitis B virus isolates from patients with hepatocellular carcinoma. Hepatology. 2007; 45: 277–85. DOI: 10.1002/hep.21529.

20. Raimondo G, Locarnini S, Pollicino T, et al. Update of the statements on biology and clinical impact of occult hepatitis B virus infection. J Hepatol. 2019; 71 (2): 397–408. DOI: 10.1016/j.jhep.2019.03.034.

21. Torbenson M, Thomas DL. Occult hepatitis B. Lancet Infect Dis. 2002; 2: 479–86. DOI: 10.1016/S 1473–3099 (02)00345–6.

22. Gremese E, Gasbarrini A, Ferraccioli G. HBV and targeted synthetic (ts)DMARDs: what have we learned from bDMARDs and tsDMARDs? RMD Open. 2020; 6 (1): e001171. DOI: 10.1136/rmdopen-2020–001171.

23. Ridola L, Zullo A, Laganà B, et al. Hepatitis B (HBV) reactivation in patients receiving biologic therapy for chronic inflammatory diseases in clinical practice. Ann Ist Super Sanita. 2021; 57 (3): 244–248. DOI: 10.4415/ANN_21_03_08.

24. Ye J, Xie P, Zhou Z et al. Protective Role of Rheumatic Diseases Against Hepatitis B Virus Infection and Human Leukocyte Antigen B 27 Highlighted. Front Med (Lausanne). 2022; 9: 814423. DOI: 10.3389/fmed.2022.814423.

25. Каратеев А. Е., Гонтаренко Н. В., Цурган А. В. и др. Вирусные гепатиты B и C как коморбидная патология при ревматических заболеваниях: анализ данных клиники ФГБНУ НИИР им. В. А. Насоновой за 4 года. Научно-практическая ревматология. 2016; 54 (3): 318–323. DOI: http://dx.doi.org/10.14412/1995–4484–2016–318–323.

26. H. A. Torres, M. Davila, Reactivation of hepatitis B virus and hepatitis C virus in patients with cancer. Nat Rev Clin Oncol. 2012; 9 (3): 156–66. DOI: 10.1038/nrclinonc.2012.1.

27. Perrillo RP, Gish R, Falck-Ytter YT. American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015; 148 (1): 221–44. e3. DOI: 10.1053/j.gastro.2014.10.038.

28. Xuan D, Yu Y, Shao L, et al. Hepatitis reactivation in patients with rheumatic diseases after immunosuppressive therapy-a report of long-term follow-up of serial cases and literature review. Clin Rheumatol. 2014; 33: 577–86. DOI: 10.1007/ s10067–013–2450–9.

29. Reddy KR, Beavers KL, Hammond SP, et al. American gastroenterological association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015; 148: 215–9. DOI: 10.1053/j.gastro.2014.10.039.

30. Chen Y-M, Huang W-N, Wu Y-D, et al. Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib: a real-world study. Ann Rheum Dis. 2018; 77: 780–2. DOI: 10.1136/annrheumdis-2017–211322.

31. Harigai M, Winthrop K, Takeuchi T, et al. Evaluation of hepatitis B virus in clinical trials of baricitinib in rheumatoid arthritis. RMD Open 2020; 6: e001095. DOI: 10.1136/rmdopen-2019–001095.

32. Wu YL, Ke J, Zhang BY, Zhao D. Hepatitis B virus reactivation in rheumatoid arthritis. World J Clin Cases. 2022 Jan 7; 10 (1): 12–22. DOI: 10.12998/wjcc.v10.i1.12.

33. Wang ST, Tseng CW, Hsu CW et al. Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib. Int J Rheum Dis. 2021; 24 (11): 1362–1369. DOI: 10.1111/1756–185X.14217.

34. Lin YC, Chen YJ, Lee SW et al. Long-Term Safety in HBsAg-Negative, HBcAb-Positive Patients with Rheumatic Diseases Receiving Maintained Steroid Therapy after Pulse Therapy. J Clin Med. 2021; 10 (15): 3296. DOI: 10.3390/jcm10153296.

35. Chiu HY, Hui RC, Huang YH et al. Safety Profile of Secukinumab in Treatment of Patients with Psoriasis and Concurrent Hepatitis B or C: A Multicentric Prospective Cohort Study. Acta Derm Venereol. 2018; 98: 829–834. DOI: 10.2340/00015555–2989.

36. Kuo MH, Tseng CW, Lu MC et al. Risk of Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients Undergoing Tocilizumab-Containing Treatment. Dig Dis Sci. 2021; 66 (11): 4026–4034. DOI: 10.1007/s10620–020–06725–1.

37. Lin W. T., Chen Y. M., Chen D. Y. et al. Increased risk of hepatitis B virus reactivation in systemic lupus erythematosus patients receiving immunosuppressants: a retrospective cohort study. Lupus. 2018; 27 (1): 66–75. DOI: 10.1177/0961203317711009.

38. Koutsianas C., Thomas K., Vassilopoulos D. Reactivation of hepatitis B virus infection in rheumatic diseases: risk and management considerations. Ther Adv Musculoskelet Dis. 2020; 12: 1759720X20912646. DOI: 10.1177/1759720X20912646.

39. Busa S, Kavanaugh A, Drug safety evaluation of apremilast for treating psoriatic arthritis, Expert Opin. Drug Saf. 2015; 14 (6): 979–985. DOI: 10.1517/14740338.2015.1031743.

40. Kuo MH, Tseng CW, Lee CH et al. Moderate Risk of Hepatitis B Virus Reactivation in HBsAg–/HBcAb+ Carriers Receiving Rituximab for Rheumatoid Arthritis. Sci Rep. 2020; 10 (1): 2456. DOI: 10.1038/s41598–020–59406–4.

41. Kim PS, Ho GY, Prete PE, et al. Safety and efficacy of abatacept in eight rheumatoid arthritis patients with chronic hepatitis B. Arthritis Care Res. 2012; 64: 1265–8. DOI: 10.1002/acr.21654.

42. Duncan JR, Orlowski TJ, Elewski BE. Safety of guselkumab in hepatitis B virus infection. Dermatol Online J. 2019; 25 (10): 13030/qt47h636rx.

43. Koike Y, Fujiki Y, Higuchi M et al. An interleukin-17 inhibitor successfully treated a complicated psoriasis and psoriatic arthritis patient with hepatitis B virus infection and end-stage kidney disease on hemodialysis. JAAD Case Rep. 2019; 5: 150–152. DOI: 10.1016/j.jdcr.2018.11.016.

44. Lora V, Graceffa D, De Felice C, et al. Treatment of severe psoriasis with ixekizumab in a liver transplant recipient with concomitant hepatitis B virus infection. Dermatol Ther. 2019; 32: e12909. DOI: 10.1111/dth.12909.

45. Hung MH, Tien YC, Chiu YM. Risk factors for losing hepatitis B virus surface antibody in patients with HBV surface antigen negative/surface antibody positive serostatus receiving biologic disease-modifying anti-rheumatic drugs: a nested case-control study. Adv Rheumatol. 2021; 61 (1): 22. DOI: 10.1186/s42358–021–00173–9.

46. Tien YC, Yen HH, Li CF et al. Changes in hepatitis B virus surface antibody titer and risk of hepatitis B reactivation in HBsAg-negative / HBcAb-positive patients undergoing biologic therapy for rheumatic diseases: a prospective cohort study. Arthritis Res Ther. 2018; 20: 246. DOI: 10.1186/s13075–018–1748-z.

47. Pei SN, Ma MC, Wang MC, et al. Analysis of hepatitis B surface antibody titers in B cell lymphoma patients after rituximab therapy. Ann Hematol. 2012; 91: 1007–12. DOI: 10.1007/s00277–012–1405–6.

48. Chen MH, Lee IC, Chen MH et al. Abatacept is second to rituximab at risk of HBsAg reverse seroconversion in patients with rheumatic disease. Ann Rheum Dis. 2021; 80 (11): 1393–1399. DOI: 10.1136/annrheumdis-2021–220774.

49. Белов Б. С., Муравьева Н. В., Тарасова Г. М. К проблеме реактивации вирусного гепатита B при ревматических заболеваниях: риски и вопросы курации. Медицинский cовет. 2020; (19): 98–106. https://doi.org/10.21518/2079–701X-2020–19–98–106

50. Guo L, Wang D, Ouyang X, et al. Recent Advances in HBV Reactivation Research. Biomed Res Int. 2018 Dec 26; 2018: 2931402. DOI: 10.1155/2018/2931402.

51. Taves MD, Ashwell JD. Glucocorticoids in T cell development, differentiation and function. Nat Rev Immunol. 2021; 21 (4): 233–243. DOI: 10.1038/s41577–020–00464–0.

52. Gwak G-Y, Koh KC, Kim H-Y. Fatal hepatic failure associated with hepatitis B virus reactivation in a hepatitis B surface antigen-negative patient with rheumatoid arthritis receiving low dose methotrexate. Clin Exp Rheumatol. 2007; 25: 888–889.

53. Zhong Z, Liao W, Dai L, et al. Average corticosteroid dose and risk for HBV reactivation and hepatitis flare in patients with resolved hepatitis B infection. Ann Rheum Dis. 2022; 81 (4): 584–591. DOI: 10.1136/annrheumdis-2021–221650.

54. Wong GL, Wong VW, Yuen BW, et al. Risk of hepatitis B surface antigen seroreversion after corticosteroid treatment in patients with previous hepatitis B virus exposure. J Hepatol. 2020; 72 (1): 57–66. DOI: 10.1016/j.jhep.2019.08.023.

55. Xuan D, Yu Y, Shao L, et al. Hepatitis reactivation in patients with rheumatic diseases after immunosuppressive therapy – a report of long-term follow-up of serial cases and literature review. Clin Rheumatol. 2014; 33 (4): 577–86. DOI: 10.1007/s10067–013–2450–9.

56. Zanati SA, Locarnini SA, Dowling JP, et al. Hepatic failure due to fibrosing cholestatic hepatitis in a patient with pre-surface mutant hepatitis B virus and mixed connective tissue disease treated with prednisolone and chloroquine. J Clin Virol. 2004; 31 (1): 53–7. DOI: 10.1016/j.jcv.2004.02.013.

57. 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 (6): 519–22. DOI: 10.2169/internalmedicine.37.519.

58. Cheng J, Li JB, Sun QL, Li X. Reactivation of hepatitis B virus after steroid treatment in rheumatic diseases. J Rheumatol. 2011; 38 (1): 181–2. DOI: 10.3899/jrheum.100692.

59. Hatano M., Mimura T., Shimada A., et al. Hepatitis B virus reactivation with corticosteroid therapy in patients with adrenal insufficiency. Endocrinol Diabetes Metab. 2019; 2 (3): e00071. DOI: 10.1002/edm2.71.

60. Pattullo V. Hepatitis B reactivation in the setting of chemotherapy and immunosuppression – prevention is better than cure. World J Hepatol. 2015; 7 (7): 954–67. DOI: 10.4254/wjh.v7.i7.954.

61. Sakkas LI, Mavropoulos A, Bogdanos DP. Phosphodiesterase 4 Inhibitors in Immune-mediated Diseases: Mode of Action, Clinical Applications, Current and Future Perspectives. Curr Med Chem. 2017; 24 (28): 3054–3067. DOI: 10.2174/09 29867324666170530093902.

62. Zhou Q, Zhang Q, Wang K et al. Anti-rheumatic drug-induced hepatitis B virus reactivation and preventive strategies for hepatocellular carcinoma. Pharmacol Res. 2022; 178: 106181. DOI: 10.1016/j.phrs.2022.106181.

63. Tan J., Zhou J., Zhao P., Wei J. Prospective study of HBV reactivation risk in rheumatoid arthritis patients who received conventional disease-modifying antirheumatic drugs. Clin Rheumatol. 2012; 31 (8): 1169–1175. DOI: 10.1007/s10067–012–1988–2.

64. Mo YQ, Liang AQ, Ma JD, et al. Discontinuation of antiviral prophylaxis correlates with high prevalence of hepatitis B virus (HBV) reactivation in rheumatoid arthritis patients with HBV carrier state: a real-world clinical practice. BMC Musculoskelet Disord. 2014; 15: 449.

65. Gane EJ, Deary G, Piratvisuth T et al. Renal function is improved for chronic hepatitis B (CHB) patients treated with telbivudine. Hepatology 2011; 54: 1044A.

66. Abdel-Noor R, Watany M, Abd-Elsalam S, et al. Is Hepatitis B Surface Antigen (HBsAg) Enough Alone as a Screening Test for HBV Infection in Rheumatic Disease Patients Before Starting Immunosuppressive Therapies? A Cross-sectional Study. Infect Disord Drug Targets. 2020; 20 (6): 878–883. DOI: 10.2174/18715265 19666191212094141.

67. Pattullo V. Prevention of Hepatitis B reactivation in the setting of immunosuppression. Clin Mol Hepatol. 2016; 22 (2): 219–37. DOI: 10.3350/cmh.2016.0024.

68. Terrault NA, Lok ASF, McMahon BJ et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018; 67: 1560–1599. DOI: 10.1002/hep.29800.

69. Bykerk VP, Akhavan P, Hazlewood GS, et al. Canadian Rheumatology Association recommendations for pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs. J Rheumatol 2012; 39: 1559–82.

70. Singh JA, Saag KG, Bridges SL, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis: ACR RA treatment recommendations. Arthritis Rheumatol. 2016 Jan; 68 (1): 1–26. DOI: 10.1002/art.39480.

71. Schmajuk G, Li J, Evans M, et al. RISE registry reveals potential gaps in medication safety for new users of biologics and targeted synthetic DMARDs. Semin Arthritis Rheum. 2020; 50 (6): 1542–1548. DOI: 10.1016/j.semarthrit.2020.03.003.

72. Mohareb AM, Patel NJ, Fu X, et al. Screening for Hepatitis B Virus Prior to Initiating Tocilizumab and Tofacitinib in Patients with Rheumatic Diseases: A Cross-sectional Study. J Rheumatol. 2022; 49: 104–9. DOI: 10.3899/jrheum.210257.

73. Sarin SK, Kumar M, Lau GK et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016; 10: 1–98. DOI: 10.1007/s12072–015–9675–4.

74. Mok CC. Hepatitis B and C infection in patients undergoing biologic and targeted therapies for rheumatic diseases. Best Pract Res Clin Rheumatol. 2018; 32 (6): 767–80. DOI: 10.1016/j.berh.2019.03.008.

75. Akiyama S, Cotter TG, Sakuraba A. Risk of hepatitis B virus reactivation in patients with autoimmune diseases undergoing non-tumor necrosis factor-targeted biologics. World J Gastroenterol. 2021; 27 (19): 2312–2324. DOI: 10.3748/wjg.v27.i19.2312.

76. Cacoub P, Terrier B. Hepatitis B-related autoimmune manifestations. Rheum Dis Clin North Am. 2009; 35 (1): 125–37. DOI: 10.1016/j.rdc.2009.03.006.

77. Vukatana G, Gamal N, Trevisani M, et al. Serological prevalence of hepatitis B virus infection among patients with different rheumatic disease: A prospective study. Ann Rheum Dis. 2014; 73 (Suppl 2): 281. DOI: 10.1136/annrheumdis-2014-eular.5467.

78. Cacoub B, Saadoun D, Bourliere M, et al. Hepatitis B virus genotypes and extrahepatic manifestations. J Hepatol. 2005; 43: 764–70. DOI: 10.1016/j.jhep.2005.05.029.

79. Tung CH, Li CY, Chen YC, Chen YC. Association between nucleos(t)ide analogue therapy for hepatitis B and Sjögren's syndrome: 15-year analysis of the national database of Taiwan. J Viral Hepat. 2021; 28 (5): 809–816. DOI: 10.1111/jvh.13481.

80. Wongtrakul W, Charoenngam N, Ponvilawan B et al. Hepatitis B virus infection and risk of gastric cancer: a systematic review and meta-analysis. Minerva Gastroenterol (Torino). 2021 Jul 9. DOI: 10.23736/S2724–5985.21.02946–6.

81. Huang CE, Chang JJ, Wu YY, et al. Different impacts of common risk factors associated with thrombocytopenia in patients with hepatitis B virus and hepatitis C virus infection. Biomed J. 2021 Sep 8: S 2319–4170 (21) 00113-X. DOI: 10.1016/j.bj.2021.09.001.

82. Joo EJ, Chang Y, Yeom JS, et al. Hepatitis B infection is associated with an increased incidence of thrombocytopenia in healthy adults without cirrhosis. J Viral Hepat. 2017; 24 (3): 253–258. DOI: 10.1111/jvh.12642.

83. Stasi R, Chia LW, Kalkur P, et al. Pathobiology and treatment of hepatitis virus-related thrombocytopenia. Mediterr J Hematol Infect Dis. 2009; 1 (3): e2009023. DOI: 10.4084/MJHID.2009.023.

84. Moore AH. Thrombocytopenia in Cirrhosis: A Review of Pathophysiology and Management Options. Clin Liver Dis (Hoboken). 2019; 14 (5): 183–186. DOI: 10.1002/cld.860.

85. Huang CE, Chen YY, Chang JJ, et al. Thrombopoietic cytokines in patients with hepatitis C virus-associated immune thrombocytopenia. Hematology. 2017; 22 (1): 54–60. DOI: 10.1080/10245332.2016.1204493.

86. Christodoulou D, Katsanos K, Zervou E, et al. Platelet IgG antibodies are significantly increased in chronic liver disease. Ann Gastroenterol. 2011; 24 (1): 47–52.

87. Pradella P, Bonetto S, Turchetto S, et al. Platelet production and destruction in liver cirrhosis. J Hepatol. 2011 May; 54 (5): 894–900. DOI: 10.1016/j.jhep.2010.08.018.

88. Zufferey A, Kapur R, Semple JW. Pathogenesis and Therapeutic Mechanisms in Immune Thrombocytopenia (ITP). J Clin Med. 2017 Feb 9; 6 (2): 16. DOI: 10.3390/jcm6020016.