Chronic Rejection Preceded by Central Perivenulitis, Rapidly Ensuing After Liver Transplantation in a Pediatric Patient

ABSTRACT

A 15-year-old boy who underwent liver transplantation for fulminant Wilson's disease, presented with elevated transaminases 2 months post-transplant. He had recently seroconverted from previous Epstein-Barr virus (EBV) naive status and by polymerase chain reaction (PCR) had increasing viral load copies of EBV in blood. A liver biopsy was obtained 6 weeks post-transplant, which showed isolated central perivenulitis (CP). His immunosuppresion was reduced and antiviral therapy was added with subsequent increase in liver transaminases. A second liver biopsy 6 weeks later again showed isolated CP. Subsequent further reduction in immunosuppression was followed by the appearance of portal-based moderate acute cellular rejection that was resistant to immunosuppressive treatment and rapidly evolved into ductopenic chronic rejection. This case report underlines the difficulties in interpreting isolated perivenulitis, especially in the setting of EBV seroconversion, and suggests that it may not only represent a form of acute rejection but also a predictor of rapidly progressing chronic rejection.

KEYWORDS

Isolated central perivenulitis - liver transplantation - pediatric - chronic rejection - EBV hepatitis

REFERENCES

• 1 Ben-Ari Z, Amlot P, Lachmanan S R et al.. Postransplantation lymphoproliferative disorder in liver recipients: characteristics, management, and outcome.  Liver Transpl Surg. 1999;  5 184-191
• 2 Holmes R D, Orban-Eller K, Karrer F R et al.. Response of elevated Epstein-Barr virus DNA levels to therapeutic changes in pediatric liver transplant patients: 56-month follow up and outcome.  Transplantation. 2002;  74 367-372
• 3 Lee T C, Savoldo B, Rooney C M et al.. Quantitative EBV viral loads and immunosuppression alterations can decrease PTLD incidence in pediatric liver transplant recipients.  Am J Transplant. 2005;  5 2222-2228
• 4 Jang J Y, Kim K M, Lee Y J et al.. Quantitative Epstein-Barr virus viral load monitoring in pediatric liver transplantation.  Transplant Proc. 2008;  40 2546-2548
• 5 Kogan D L, Burroughs M, Emre S et al.. Prospective longitudinal analysis of quantitative Epstein-Barr virus polymerase chain reaction in pediatric liver transplant recipients.  Transplantation. 1999;  67 1068-1070
• 6 Muiesan P, Vergani D, Mieli-Vergani G. Liver transplantation in children.  J Hepatol. 2007;  46 340-348
• 7 Ng V, Anand R, Martz K, Fecteau A. Liver retransplantation in children: a SPLIT database analysis of outcome and predictive factors for survival.  Am J Transplant. 2008;  8 386-395
• 8 Shepherd R W, Turmelle Y, Nadler M et al.. Risk factors for rejection and infection in pediatric liver transplantation.  Am J Transplant. 2008;  8 396-403
• 9 Demetris A J, Adeyi O, Bellamy C O et al.. Liver biopsy interpretation for causes of late liver allograft dysfunction.  Hepatology. 2006;  44 489-501
• 10 Demetris A J. Central venulitis in liver allografts: considerations of differential diagnosis.  Hepatology. 2001;  33 1329-1330
• 11 Krasinskas A M, Demetris A J, Poterucha J J, Abraham S C. The prevalence and natural history of untreated isolated central perivenulitis in adult allograft livers.  Liver Transpl. 2008;  14 625-632
• 12 Banff schema for grading liver allograft rejection: an international consensus document.  Hepatology. 1997;  25 658-663
• 13 Mieli-Vergani G, Vergani D. De novo autoimmune hepatitis after liver transplantation.  J Hepatol. 2004;  40 3-7
• 14 Demetris A, Adams D, Bellamy C et al.. Update of the International Banff Schema for Liver Allograft Rejection: working recommendations for the histopathologic staging and reporting of chronic rejection.  Hepatology. 2000;  31 792-799
• 15 Neil D A, Hubscher S G. Histologic and biochemical changes during the evolution of chronic rejection of liver allografts.  Hepatology. 2002;  35 639-651
• 16 D'Antiga L, Dhawan A, Portmann B et al.. Late cellular rejection in paediatric liver transplantation: aetiology and outcome.  Transplantation. 2002;  73 80-84
• 17 Abraham S C, Freese D K, Ishitani M B et al.. Significance of central perivenulitis in pediatric liver transplantation.  Am J Surg Pathol. 2008;  32 1479-1488