Role of tissue C4d in differentiation between acute rejection and HCV recurrence after living donor liver transplantation
DOI:
https://doi.org/10.18203/2349-3933.ijam20203118Keywords:
Acute rejection, Hepatitis C recurrence, Liver biopsy, Liver transplantationAbstract
Background: Liver biopsy represents the gold standard for diagnosis of acute rejection and HCV recurrence after liver transplantation; never the less discrimination can be difficult due to similar display of alterations in liver specimen. Therefore, a specific marker expressed only in rejection but not in HCV recurrence would be a great asset to differentiate between both conditions. The aim of this study was to assess the role of tissue C4d complement fragments in liver biopsy as a marker for differentiating between acute rejection and HCV recurrence in recipients post LDLT.
Methods: A case control study on 25 recipients after liver transplantation with the suspicion of either acute rejection or HCV disease recurrence, patients were classified according to pathological finding into two groups, Group 1: patients with acute rejection (n=13), Group 2: patients with HCV recurrence (n=12), The C4d was evaluated by immunohistochemical staining of the formalin-fixed, paraffin-embedded tissue in different liver compartments.
Results: C4D staining of all the studied tissue compartments (Sinusoids, portal vein endothelium, hepatic vein endothelium, arterial internal elastic lining, portal stroma, bile ducts) had high specificity (100%) and positive predictive value (100%) in diagnosis of rejection cases except portal vein endothelium. (Specificity 91.7%, positive predictive value 88.9%).
Conclusions: Tissue C4d staining was almost present in rejection cases only; further studies on larger cohort are required to stand on standard diagnostic criteria for C4d to be included in diagnosis of acute rejection after liver transplantation as its role in other organ transplantation.
References
Charlton M. Natural history of hepatitis C and outcomes following liver transplantation. Clin Liver Dis. 2003;7(3):585-602.
Schmeding M, Dankof A, Krenn V, Krukemeyer MG, Koch M, Spinelli A, et al. C4d in acute rejection after liver transplantation a valuable tool in differential diagnosis to hepatitis C recurrence. Am J Transplant. 2006;6(53):523-30.
Regev A, Molina E, Moura R, Bejarano PA, Khaled A, Ruiz P, et al. Reliability of histopathologic assessment for the differentiation of recurrent hepatitis C from acute rejection after liver transplantation. Liver Transpl. 2004;10(10):1233-9.
Petrovic LM. Early recurrence of hepatitis C virus infection after liver transplantation. Liver Transpl. 2006;12:17-22.
Jain A, Ryan C, Mohanka R, Orloff M, Abt P, Romano J, et al. Characterization of CD4, CDS, CD56 positive lymphocytes and C4d deposits to distinguish acute cellular rejection from recurrent hepatitis C in post-liver transplant biopsies. Clin Transplant. 2006;20:624-33.
Schmeding M, Kienlein S, Röcken C, Neuhaus R, Neuhaus P, Heidenhain C, et al. ELISA-based detection of C4d after liver transplantation -A helpful tool for differential diagnosis between acute rejection and HCV-recurrence? Transplant Immunol. 2010;23:156-60.
Ingulli E. Mechanism of cellular rejection in transplantation. Pediatr Nephrol. 2008;25(1):61-74.
Hubscher S, Clouston A. Transplantation pathology. In: Burt A, Portmann B, Ferrell L (eds). Macsween Pathology of Liver; 6th Edn; Elsevier Ltd; Chapter 15; 2011:853-933.
Kozlowski T, Andreoni K, Schmitz J, Hideo Hayashi P, Nickeleit V. Sinusoidal C4d deposits in liver allografts indicate an antibody-mediated response: Diagnostic considerations in the evaluation of liver allografts. Liver Transpl. 2012;18(6):641-58.
Feucht HE, Schneeberger H, Hillebrand G, Burkhardt K, Weiss M, Riethmüller G, et al. Capillary deposition of C4d complement fragment and early renal graft loss. Kidney Int. 1993;43:1333-8.
Collins AB, Schneeberger EE, Pascual MA, Saidman SL, Williams WW, Tolkoff-Rubin N, et al. Complement activation in acute humoral renal allograft rejection: diagnostic significance of C4d deposits in peritubular capillaries. J Am Soc Nephrol. 1999;10:2208-14.
Berger SP, Roos A, Daha MR. Complement and the kidney: what the nephrologist needs to know in 2006? Nephrol Dial Transplant. 2005;20:2613-9.
Herzenberg AM, Gill JS, Djurdjev O, Magil AB. C4d deposition in acute rejection: an independent long-term prognostic factor. J Am Soc Nephrol. 2002;13:234-41.
Krukemeyer MG, Moeller J, Morawietz L, Rudolph B, Neumann U, Theruvath T, et al. Description of B lymphocytes and plasma cells, complement, and chemokines/receptors in acute liver allograft rejection. Transplantation. 2004;78:65-70.
Van der Plaats A. Anatomy and physiology of the liver. Available at: http://dissertations.ub.rug.n1/FILES/faculties/medicine / 2005/a.van.der.plaats/c2.pdf. 2012.
