CC BY 4.0 · Glob Med Genet 2023; 10(03): 229-233
DOI: 10.1055/s-0043-1772771
Review Article

Review: Advances in the Pathogenesis and Treatment of Immune Thrombocytopenia Associated with Viral Hepatitis

Yanmei Xu
1   State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, People's Republic of China
2   Tianjin Institutes of Health Science, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, People's Republic of China
,
Yunfei Chen
1   State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, People's Republic of China
2   Tianjin Institutes of Health Science, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, People's Republic of China
,
Lei Zhang
1   State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, People's Republic of China
2   Tianjin Institutes of Health Science, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, People's Republic of China
› Author Affiliations
Funding/Acknowledgments This project was supported by the CAMS Innovation Fund for Medical Sciences (CIFMS) (grant numbers 2020-I2M-C&T-B-086 and 2022-I2M-2-003) and the National Natural Science Foundation of China (grant numbers 82270152 and 81970121).

Abstract

Hepatitis B virus and hepatitis C virus are the hepatitis subtypes that most commonly induce immune thrombocytopenia (ITP). Although the pathogenesis of viral hepatitis-associated ITP remains unclear, it may involve antibody cross-reactivity due to molecular mimicry, the formation of virus-platelet immune complexes, and T cell-mediated suppression of bone marrow hematopoiesis. Moreover, there is significant correlation between platelet count and the severity of viral hepatitis, the risk of progression to liver cirrhosis, and clinical prognosis. However, treatment of viral hepatitis-associated ITP is hindered by some antiviral drugs. In this review, we summarize research progress to date on the pathogenesis and treatment of viral hepatitis-related ITP, hoping to provide a reference for clinical diagnosis and treatment.

Authors' Contribution

Y.X. was responsible for the main data collation and writing, and Y.C. and L.Z. were responsible for the guidance and revision of the content.




Publication History

Article published online:
24 August 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 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 2022; 45 (05) 788-797
  • 2 Rajan SK, Espina BM, Liebman HA. Hepatitis C virus-related thrombocytopenia: clinical and laboratory characteristics compared with chronic immune thrombocytopenic purpura. Br J Haematol 2005; 129 (06) 818-824
  • 3 Liu J, Liang W, Jing W, Liu M. Countdown to 2030: eliminating hepatitis B disease, China. Bull World Health Organ 2019; 97 (03) 230-238
  • 4 Hajarizadeh B, Grebely J, Dore GJ. Epidemiology and natural history of HCV infection. Nat Rev Gastroenterol Hepatol 2013; 10 (09) 553-562
  • 5 Tejima K, Masuzaki R, Ikeda H. et al. Thrombocytopenia is more severe in patients with advanced chronic hepatitis C than B with the same grade of liver stiffness and splenomegaly. J Gastroenterol 2010; 45 (08) 876-884
  • 6 Chiao EY, Engels EA, Kramer JR. et al. Risk of immune thrombocytopenic purpura and autoimmune hemolytic anemia among 120 908 US veterans with hepatitis C virus infection. Arch Intern Med 2009; 169 (04) 357-363
  • 7 Wei G, Bai O. Clinical analysis of 48 cases of HBsAg and HCV-Ab positive immune thrombocytopenic purpura. Chin J Lab Diagnosis 2009; 13 (12) 1763-1765
  • 8 Albert LJ, Inman RD. Molecular mimicry and autoimmunity. N Engl J Med 1999; 341 (27) 2068-2074
  • 9 Zhang W, Nardi MA, Borkowsky W, Li Z, Karpatkin S. Role of molecular mimicry of hepatitis C virus protein with platelet GPIIIa in hepatitis C-related immunologic thrombocytopenia. Blood 2009; 113 (17) 4086-4093
  • 10 Li Z, Nardi MA, Wu J, Pan R, Zhang W, Karpatkin S. Platelet fragmentation requires a specific structural conformation of human monoclonal antibody against beta3 integrin. J Biol Chem 2008; 283 (06) 3224-3230
  • 11 Peterson JA, Nelson TN, Kanack AJ, Aster RH. Fine specificity of drug-dependent antibodies reactive with a restricted domain of platelet GPIIIA. Blood 2008; 111 (03) 1234-1239
  • 12 Nagamine T, Ohtuka T, Takehara K, Arai T, Takagi H, Mori M. Thrombocytopenia associated with hepatitis C viral infection. J Hepatol 1996; 24 (02) 135-140
  • 13 Sanjo A, Satoi J, Ohnishi A, Maruno J, Fukata M, Suzuki N. Role of elevated platelet-associated immunoglobulin G and hypersplenism in thrombocytopenia of chronic liver diseases. J Gastroenterol Hepatol 2003; 18 (06) 638-644
  • 14 Lozach PY, Lortat-Jacob H, de Lacroix de Lavalette A. et al. DC-SIGN and L-SIGN are high affinity binding receptors for hepatitis C virus glycoprotein E2. J Biol Chem 2003; 278 (22) 20358-20366
  • 15 Zahn A, Jennings N, Ouwehand WH, Allain JP. Hepatitis C virus interacts with human platelet glycoprotein VI. J Gen Virol 2006; 87 (Pt 8): 2243-2251
  • 16 de Almeida AJ, Campos-de-Magalhães M, de Melo Marçal OP. et al. Hepatitis C virus-associated thrombocytopenia: a controlled prospective, virological study. Ann Hematol 2004; 83 (07) 434-440
  • 17 Shi J, Kokubo Y, Wake K. Expression of P-selectin on hepatic endothelia and platelets promoting neutrophil removal by liver macrophages. Blood 1998; 92 (02) 520-528
  • 18 Zeldis JB, Mugishima H, Steinberg HN, Nir E, Gale RP. In vitro hepatitis B virus infection of human bone marrow cells. J Clin Invest 1986; 78 (02) 411-417
  • 19 Hui CK, Sun J, Au WY. et al. Occult hepatitis B virus infection in hematopoietic stem cell donors in a hepatitis B virus endemic area. J Hepatol 2005; 42 (06) 813-819
  • 20 Weng HL, Feng DC, Radaeva S. et al. IFN-γ inhibits liver progenitor cell proliferation in HBV-infected patients and in 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet-fed mice. J Hepatol 2013; 59 (04) 738-745
  • 21 Lei S, Lan Y, Shi Y, Ying Z, Li Y. Replication of hepatitis B virus in hematopoietic stem cells and the effect on its immune activity. Chinese Journal of Infectious Diseases 2010; 28 (03) 144-149
  • 22 Pockros PJ, Duchini A, McMillan R, Nyberg LM, McHutchison J, Viernes E. Immune thrombocytopenic purpura in patients with chronic hepatitis C virus infection. Am J Gastroenterol 2002; 97 (08) 2040-2045
  • 23 Zhang L, Li H, Zhao H, Ji L, Yang R. Hepatitis C virus-related adult chronic idiopathic thrombocytopenic purpura: experience from a single Chinese center. Eur J Haematol 2003; 70 (03) 196-197
  • 24 Wang H, Innes H, Hutchinson SJ. et al. The prevalence and impact of thrombocytopenia, anaemia and leucopenia on sustained virological response in patients receiving hepatitis C therapy: evidence from a large ‘real world’ cohort. Eur J Gastroenterol Hepatol 2016; 28 (04) 398-404
  • 25 Iga D, Tomimatsu M, Endo H, Ohkawa S, Yamada O. Improvement of thrombocytopenia with disappearance of HCV RNA in patients treated by interferon-alpha therapy: possible etiology of HCV-associated immune thrombocytopenia. Eur J Haematol 2005; 75 (05) 417-423
  • 26 Shrestha R, McKinley C, Bilir BM, Everson GT. Possible idiopathic thrombocytopenic purpura associated with natural alpha interferon therapy for chronic hepatitis C infection. Am J Gastroenterol 1995; 90 (07) 1146-1147
  • 27 Pan Y. A preliminary study on the efficacy of interferon and hormone treatment for severe hepatitis. Zhonghua Jizhen Yixue Zazhi 2002; 11 (03) 205
  • 28 Feng R, Liu Y, Zhu XL. et al. Recombinant human thrombopoietin increases platelet count in severe thrombocytopenic patients with hepatitis B-related cirrhosis: multicentre real-world observational study. J Viral Hepat 2022; 29 (05) 306-316
  • 29 McHutchison JG, Dusheiko G, Shiffman ML. et al; TPL102357 Study Group. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med 2007; 357 (22) 2227-2236
  • 30 Afdhal NH, Dusheiko GM, Giannini EG. et al. Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for effective antiviral therapy. Gastroenterology 2014; 146 (02) 442-52.e1
  • 31 Moore AH. Thrombocytopenia in cirrhosis: a review of pathophysiology and management options. Clin Liver Dis (Hoboken) 2019; 14 (05) 183-186
  • 32 Terrault N, Chen YC, Izumi N. et al. Avatrombopag before procedures reduces need for platelet transfusion in patients with chronic liver disease and thrombocytopenia. Gastroenterology 2018; 155 (03) 705-718
  • 33 Akahoshi T, Tomikawa M, Kawanaka H. et al. Laparoscopic splenectomy with interferon therapy in 100 hepatitis-C-virus-cirrhotic patients with hypersplenism and thrombocytopenia. J Gastroenterol Hepatol 2012; 27 (02) 286-290
  • 34 Bárcena R, Gil-Grande L, Moreno J. et al. Partial splenic embolization for the treatment of hypersplenism in liver transplanted patients with hepatitis C virus recurrence before peg-interferon plus ribavirin. Transplantation 2005; 79 (11) 1634-1635
  • 35 Zhang XH, Feng R, Xu LP. et al. Immunosuppressive treatment combined with nucleoside analog is superior to nucleoside analog only in the treatment of severe thrombocytopenia in patients with cirrhosis associated with hepatitis B in China: a multicenter, observational study. Platelets 2015; 26 (07) 672-679
  • 36 Lee HL, Bae SH, Jang B. et al. Reactivation of hepatitis C virus and its clinical outcomes in patients treated with systemic chemotherapy or immunosuppressive therapy. Gut Liver 2017; 11 (06) 870-877
  • 37 Torres HA, Davila M. Reactivation of hepatitis B virus and hepatitis C virus in patients with cancer. Nat Rev Clin Oncol 2012; 9 (03) 156-166
  • 38 Lu XJ, Li XH, Yuan ZX. et al. Assessment of liver fibrosis with the gamma-glutamyl transpeptidase to platelet ratio: a multicentre validation in patients with HBV infection. Gut 2018; 67 (10) 1903-1904
  • 39 Spengler U. Hepatic microcirculation: a critical but neglected factor for the outcome of viral hepatitis. J Hepatol 2009; 50 (03) 631-633
  • 40 European Association of the Study of the Liver. 2011 European Association of the Study of the Liver hepatitis C virus clinical practice guidelines. Liver Int 2012; 32 (Suppl. 01) 2-8