Clinical Journal of Gastroenterology

, Volume 3, Issue 5, pp 237–242 | Cite as

Autoimmune hemolytic anemia in treatment-naive chronic hepatitis C infection: a case report and review of literature

  • Robert J. Basseri
  • Michael T. Schmidt
  • Benjamin Basseri
Case Report

Abstract

The hepatitis C virus (HCV) is the most common blood-borne pathogen and currently infects over two hundred and fifty million individuals worldwide. Chronic HCV infection may result in cirrhosis, hepatocellular carcinoma, and liver failure. An exceedingly rare extrahepatic manifestation of HCV is autoimmune hemolytic anemia (AIHA). We discuss an interesting case of direct Coombs’-positive AIHA in a treatment-naive 53-year-old male with a past medical history of HCV cirrhosis, genotype 3a, who presented with fatigue, abdominal pain, and jaundice. Complete blood cell count demonstrated anemia, thrombocytopenia, elevated mean corpuscular hemoglobin and corpuscular volume worrisome for hemolytic anemia. Upon further workup, the patient was found to have increased bilirubin, reticulocyte count, and lactate dehydrogenase with concomitant direct Coombs’-positive test, consistent with the diagnosis of AIHA. A comprehensive workup was conducted to elucidate the underlying etiology of the AIHA, including malignancy, systemic lupus erythematosus (SLE), and medication side-effects. Malignancy was ruled out with an imaging and bone marrow biopsy. SLE was subsequently eliminated with a negative anti-nuclear antibody (ANA), and the patient had never received ribavirin, interferon, cephalosporins or other medications associated with drug-induced immune hemolytic anemia (DI-IHA). While the relationship between DI-IHA and HCV is well-described in the literature, primary AIHA in treatment-naive patients is a rare and intriguing extrahepatic manifestation of HCV and only four reports have been described in the literature. Given the prevalence of HCV and this interesting extrahepatic manifestation, HCV testing should be considered in patients presenting with AIHA with an otherwise negative workup and a history of parenteral or lifestyle risk factors.

Keywords

Autoimmune hemolytic anemia (AIHA) Hepatitis C virus (HCV) Extrahepatic manifestation Treatment-naive 

References

  1. 1.
    Tong MJ, El-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med. 1995;332:1463–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Alter MJ, Mast EE. The epidemiology of viral hepatitis in the United States. Gastroenterol Clin North Am. 1994;23:437–55.PubMedGoogle Scholar
  3. 3.
    Farci P, Alter HJ, Wong D, Miller RH, Govindarajan S, Engle R, Shapiro M, et al. A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. N Engl J Med. 1991;325:98–104.CrossRefPubMedGoogle Scholar
  4. 4.
    Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144:705–14.PubMedGoogle Scholar
  5. 5.
    Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med. 1999;341:556–62.CrossRefPubMedGoogle Scholar
  6. 6.
    Hassan MM, Frome A, Patt YZ, El-Serag HB. Rising prevalence of hepatitis C virus infection among patients recently diagnosed with hepatocellular carcinoma in the United States. J Clin Gastroenterol. 2002;35:266–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB. Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: a population-based study. Gastroenterology. 2004;127:1372–80.CrossRefPubMedGoogle Scholar
  8. 8.
    Fattovich G, Giustina G, Degos F, Tremolada F, Diodati G, Almasio P, et al. Morbidity and mortality in compensated cirrhosis C: a retrospective follow-up study of 384 patients. Gastroenterology. 1997;112:463–72.CrossRefPubMedGoogle Scholar
  9. 9.
    Strickland GT, El-Kamary SS, Klenerman P, Nicosia A. Hepatitis C vaccine: supply and demand. Lancet Infect Dis. 2008;8:379–86.CrossRefPubMedGoogle Scholar
  10. 10.
    Cacoub P, Renou C, Rosenthal E, Cohen P, Loury I, Loustaud-Ratti V, et al. Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. Medicine. 2000;79:47–56.CrossRefPubMedGoogle Scholar
  11. 11.
    El-Serag HB, Hampel H, Yeh C, Rabeneck L. Extrahepatic manifestations of hepatitis C among United States male veterans. Hepatology. 2002;36:1439–45.PubMedGoogle Scholar
  12. 12.
    Loustaud-Ratti V, Riche A, Liozon E, et al. Prevalence and characteristics of Sjögren’s syndrome or Sicca syndrome in chronic hepatitis C virus infection: a prospective study. J Rheumatol. 2001;28:2245–51.PubMedGoogle Scholar
  13. 13.
    Elhajj II, Sharara AI, Taher AT. Chronic hepatitis C associated with Coombs-positive hemolytic anemia. Hematol J. 2004;5:364–6.CrossRefPubMedGoogle Scholar
  14. 14.
    Srinivasan R. Autoimmune hemolytic anemia in treatment-naïve chronic hepatitis C infection. J Clin Gastroenterol. 2001;32:245–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Moccia F, Tognoni E, Boccaccio P. Autoimmune hemolytic anemia in chronic hepatitis C virus infection: an unusual extrahepatic autoimmune manifestation. Ann Ital Med Int. 2001;16:256–9.PubMedGoogle Scholar
  16. 16.
    Chao TC, Chen CY, Yang YH, Chen PM, Chang FY, Lee SD. Chronic hepatitis C virus infection associated with primary warm-type autoimmune hemolytic anemia. J Clin Gastroenterol. 2001;33:232–3.CrossRefPubMedGoogle Scholar
  17. 17.
    De Franceschi L, Fattovich G, Turrini F, Ayi K, Brugnara C, Manzato F, et al. Hemolytic anemia induced by ribavirin therapy in patients with chronic hepatitis C virus infection: role of membrane oxidative damage. Hepatology. 2000;31(4):997–1004.CrossRefPubMedGoogle Scholar
  18. 18.
    Fernández AB. An unusual case of autoimmune hemolytic anemia in treatment naïve hepatitis C virus infection. Hematology. 2006;11:385–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Chiao EY, Engels EA, Kramer JR, Pietz K, Henderson L, Giordano TP, Landgren O. Risk of immune thrombocytopenic purpura and autoimmune hemolytic anemia among 120 908 US veterans with hepatitis C virus infection. Arch Intern Med. 2009;169:357–63.CrossRefPubMedGoogle Scholar
  20. 20.
    Barbolla L, Paniagua C, Outeirino J, Prieto E, Sanchez Fayos J. Haemolytic anaemia to the alpha-interferon treatment: a proposed mechanism. Vox Sang. 1993;65:156–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Selmi C, Lleo A, Zuin M, Podda M, Rossaro L, Gershwin ME. Interferon alpha and its contribution to autoimmunity. Curr Opin Investig Drugs. 2006;7:451–6.PubMedGoogle Scholar
  22. 22.
    Johnson ST, Fueger JT, Gottschall JL. One center’s experience: the serology and drugs associated with drug-induced immune hemolytic anemia––a new paradigm. Transfusion. 2007;47:697–702.CrossRefPubMedGoogle Scholar
  23. 23.
    Garratty G. Drug-induced immune hemolytic anemia. Hematology Am Soc Hematol Educ Program. 2009:73–9.Google Scholar
  24. 24.
    Greer JP. Wintrobe’s Clinical Hematology. Vol II. Philadelphia: Lippincott; 1998:959–961.Google Scholar
  25. 25.
    Ji Q, Perchellet A, Goverman JM. Viral infection triggers central nervous system autoimmunity via activation of CD8(+) T cells expressing dual TCRs. Nat Immunol. 2010;11:628–34.CrossRefPubMedGoogle Scholar
  26. 26.
    Pivetti S, Novarino A, Merico F, et al. High prevalence of autoimmune phenomena in hepatitis C virus antibody positive patients with lymphoproliferative and connective tissue disorders. Br J Haematol. 1996;95:204–11.CrossRefPubMedGoogle Scholar
  27. 27.
    Hamaia S, Li C, Allain JP. The dynamics of hepatitis C virus binding to platelets and 2 mononuclear cell lines. Blood. 2001;98:2293–300.CrossRefPubMedGoogle Scholar
  28. 28.
    Pileri P, Uematsu Y, Campagnoli S, et al. Binding of hepatitis C virus to CD81. Science. 1998;282:938–41.CrossRefPubMedGoogle Scholar
  29. 29.
    Li X, Garon C, Fischer ER, et al. Persistence of hepatitis C virus in a human megakaryoblastic leukaemia cell line. J Viral Hepatol. 1999;6:107–14.CrossRefGoogle Scholar
  30. 30.
    Hepatitis C. World Health Organization. http://www.who.int.
  31. 31.
    Shoenfeld Y, Ehrenfeld M. Hematologic manifestations. In: Schur PH, editor. The clinical management of systemic lupus erythematosus. Philadelphia: Lippincott; 1996.Google Scholar
  32. 32.
    Hoofnagle JH, Di Bisceglie AM. The treatment of chronic viral hepatitis. N Engl J Med. 1997;336:347–56.CrossRefPubMedGoogle Scholar
  33. 33.
    Keeling DM, Isenberg DA. Haematological manifestations of systemic lupus erythematosus. Blood Rev. 1993;7:199–207.CrossRefPubMedGoogle Scholar
  34. 34.
    Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G, et al. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancet. 1998;352:1426–32.CrossRefPubMedGoogle Scholar
  35. 35.
    Cauli C, Serra G, Chessa L, Balestrieri C, Scioscia R, Lai ME, et al. Severe autoimmune hemolytic anemia in a patient with chronic hepatitis C during treatment with peginterferon alfa-2a and ribavirin. Haematologica. 2006;91:ECR26.PubMedGoogle Scholar
  36. 36.
    Reau N, Hadziyannis SJ, Messinger D, Fried MW, Jensen DM. Early predictors of anemia in patients with hepatitis C genotype 1 treated with peginterferon alfa-2a (40KD) plus ribavirin. Am J Gastroenterol. 2008;103:1981–8.CrossRefPubMedGoogle Scholar
  37. 37.
    Al-Ansari M, Weilert F, Dickson G. Interferon-induced haemolytic anaemia in hepatitis C. N Z Med J. 2008;121:78–81.PubMedGoogle Scholar
  38. 38.
    Vilar FC, Castro G, Moya MJ, Martinelli Ade L, De Santis GC, Cozac AP, et al. Autoimmune hemolytic anemia in HCV/HIV coinfected patients during treatment with pegylated alpha-2a interferon plus ribavirin. Rev Soc Bras Med Trop. 2007;40:678–80.PubMedGoogle Scholar
  39. 39.
    Oze T, Hiramatsu N, Kurashige N, Tsuda N, Yakushijin T, Kanto T, et al. Early decline of hemoglobin correlates with progression of ribavirin-induced hemolytic anemia during interferon plus ribavirin combination therapy in patients with chronic hepatitis C. J Gastroenterol. 2006;41:862–72.CrossRefPubMedGoogle Scholar
  40. 40.
    Jefferies LC. Transfusion therapy in autoimmune hemolytic anemia. Hematol Oncol Clin North Am. 1994;8:1087–104.PubMedGoogle Scholar
  41. 41.
    Ramos-Casals M, García-Carrasco M, López-Medrano F, Trejo O, Forns X, López-Guillermo A, Muñoz C, Ingelmo M, Font J. Severe autoimmune cytopenias in treatment-naive hepatitis C virus infection: clinical description of 35 cases. Medicine (Baltimore). 2003;82:87–96.CrossRefGoogle Scholar
  42. 42.
    Flores G, Cunningham-Rundles C, Newland AC, Bussel JB. Efficacy of intravenous immunoglobulin in the treatment of autoimmune hemolytic anemia: results in 73 patients. Am J Hematol. 1993;44:237–42.CrossRefPubMedGoogle Scholar
  43. 43.
    Bjorkholm M. Intravenous immunoglobulin treatment in cytopenic haematological disorders. J Intern Med. 1993;234:119–26.CrossRefPubMedGoogle Scholar
  44. 44.
    Cheung WW, Hwang GY, Tse E, Kwong YL. Alemtuzumab induced complete remission of autoimmune hemolytic anemia refractory to corticosteroids, splenectomy and rituximab. Haematologica. 2006;91:ECR13.PubMedGoogle Scholar
  45. 45.
    Ito S, Oyake T, Uchiyama T, Sugawara T, Murai K, Ishida Y. Successful treatment with cyclosporine and high-dose gamma immunoglobulin for persistent parvovirus B19 infection in a patient with refractory autoimmune hemolytic anemia. Int J Hematol. 2004;80:250–3.CrossRefPubMedGoogle Scholar
  46. 46.
    Das SS, Chaudhary R. Utility of adsorption techniques in serological evaluation of warm autoimmune haemolytic anaemia. Blood Transfus. 2009;7:300–4.PubMedGoogle Scholar
  47. 47.
    Hoffman PC. Immune hemolytic anemia––selected topics. Hematology Am Soc Hematol Educ Program. 2009:80–6.Google Scholar

Copyright information

© Springer 2010

Authors and Affiliations

  • Robert J. Basseri
    • 1
  • Michael T. Schmidt
    • 1
  • Benjamin Basseri
    • 2
  1. 1.Cedars-Sinai Medical CenterLos AngelesUSA
  2. 2.Santa MonicaUSA

Personalised recommendations