HCV RECURRENCE AFTER LIVER TRANSPLANTATION IS ASSOCIATED WITH THE DEVELOPMENT OF INTRAHEPATIC LYMPHOID FOLLICLES DESPITE IMMUNESUPPRESSION

Abstract

P796 Aims: Chronic inflammation in the liver can lead to the development of lymphoid tissue in the portal tracts. Some of these lymphoid infiltrates are highly organized, containing all characteristic components of secondary lymphoid organs, with B-lymphocytes localized in follicles and with T-cells more diffusely distributed in surrounding areas. One could speculate that these ectopic lymphoid structures fulfill similar functions as secondary lymphoid organs in the initiation and perpetuation of local immune responses. In the current study we investigated the formation of portal tract-associated lymphoid tissue (PALT) after liver transplantation, particularly in patients with hepatitis C virus (HCV) recurrence. In this setting, we can investigate a possible effect of immunosuppressive regimens on the neogenesis of lymphoid tissue induced by HCV infection of the liver graft. Results: First, the explant livers of chronic HCV patients after orthotopic liver transplantation were analysed by immunohistochemistry for the presence of PALT structures. In 9 out of 10 patients, B-cell follicles and T-cell areas were observed. Approximately one-third of all portal tracts which were examined contained B-cell follicles. Of these follicles, 4% contained a network of follicular dendritic cells (FDC) indicating of presence of an active germinal center. Most of the paracortical T cell areas contained blood vessels resembling high endothelial venules that are found in lymph nodes. These endothelial cells stained positive for the Peripheral Node Addressin (PNAD), a ligand for the adhesion receptor L-selectin. All of the microvascular endothelium in the PALT, but not the sinusoidal endothelium, stained positive for CD34 indicating neovascularization in the PALT. Next, post-transplantation biopsies of the HCV patients were analyzed. All these patients suffered from re-infection of the graft by HCV. More then a third of these patients developed PALT which contained B-cell follicles. Follicles were not found earlier as 18 months after transplantation. In this small number of post-transplantation follicles, however, no FDC-network was observed. This suggest that B-cell organization in response to HCV recurrence is relatively slow and renders inactive follicles. None of the control (HCV-negative) transplantation patients developed PALT, even at later time points after transplantation. Conclusions: HCV infection can result in the formation of ectopic lymphoid compartments in the liver graft. Immunosuppressive drugs do not prevent the formation of these PALT, although the number of B-cell follicles found in post-transplantation biopsies was significantly lower compared to liver biopsies of chronic HCV patients with end-stage liver disease. However, the role of PALT in chronic inflammatory liver diseases, like viral hepatitis, and the significance for HCV-recurrence remains unknown.