Immunohistochemical characterization of the inflammatory cell infiltrate in fulminant hepatitis B

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Poster Sessions

DP (6%) and DN ( C D 4 - C D 8 - ) (18%) cells and 40% were gd+ cells. The ratio of Naive:memory NKT cells was 1:2. NK cells (CD3-CD56+) constituted 18 4- 7% of CD2+ cells and 44 4- 16% of all CD56+ population. Less than 10% of NK cells co-expressed CD158a, CDI58b, KIRPT0, NKB1, CD4 and CD8. Most of NK cells were C D 4 - C D 8 - cells (82 43%). The majority of NK cells expressed CD161, P38 and CD1 lb (55 428%, 76 4- 18% and 80 4- 11%). Up to 64.5% of NK cells expressed CD16. CD45RA+ and CD45RO+ NK cells varied widely with a range of 5--43% and 1--49% respectively. Conclusion: The normal human liver contains distinctive IHL populations with high numbers of CD8+ and variable subsets of NKT and NK cells as well as the presence of high numbers of gamma-delta+, DP (CD4+CD8+) and DN ( C D 4 - C D 8 - ) cells.

~67-~ CHANGES OF GLUCOSE HOMEOSTASIS AND HEPATIC EXPRESSION OF GLUCOSE-REGULATING AND -UTILISING PROTEINS FOLLOWING PARTIAL HEPATECTOMY AND PORTAL BRANCH LIGATION Jannine Meyer, Yogesh Vashist, Juliane Goettsche, Dieter C. Broering, Xavier Rogiers. Department of Hepato-biliary Surgery, University

Hospital Hamburg-Eppendo~ Hamburg, Germany

Background: Liver resection for malignancies is often limited by functional defiles. In the past years, portal vein embolization has been recognised as a useful technique to prevent postoperative liver failure by providing a preoperative hypertrophy of the future remnant liver. However, consequences in hepatic function have not yet been closely evaluated. Aims: Changes in systemic glucose homeostasis and the hepatic mRNAexpression of Glucose-6-Phosphatase (G6P), Glyceraldehyd-6-PhosphateDehydrogenase (GAPDH) and Glucagon-Receptor (GR) were assessed after partial bepatectomy (PH) and portal branch ligation (PBL). Methods: 3 month old Wistar rats were used. The expression levels of G6E GAPDH and GR at different time points after surgery, beginning from 1 hour to 2 weeks, were determined using RT-PCR and Northern-Blotting techniques. Results: Systemic glucose levels transiently decreased following PBL during the prereplicative period (12 h). In contrast, PH lead to a long term decline during the prereplicative and replicative period as well. After an initial peak, the mRNA-expression of GtP specifically decreased following PH and PBL in the non-deprived, regenerating lobes 3-12 h after surgery, whereas it was again elevated during the replicative period (24 h and later). GR- and GAPDH-mRNA expression was induced during the replicative period after PH and PBL in the regenerating lobe. Conclusions: These results suggest that changes of systemic glucose levels following PH and PBL are controlled by a decrease in hepatic expression of G6E These observations show that liver regeneration after both PH and PBL is accomplished by a functional deficit which might be of clinical relevance.

~ 7 " ~ IMMUNOHISTOCHEMICAL CHARACTERIZATION OF THE INFLAMMATORY CELL INFILTRATE IN FULMINANT HEPATITIS B Munther J. Hussain l, Dimitrios P. Bogdanos 1, Yun Ma 1, Alex Knisely 2, Nedim Hadzic 3, Paolo Muiesan 2, Giorgina Mieli-Vergani3, Diego Vergani I . ~Institute of Hepatology, University College London

Medical School, London; 21nstitute of Liver Studies, King's College Hospital, London; 3Department of Child Health, King's College Hospital, London, UK The immune system is believed to play a key role in the outcome of hepatitis B virus infection, a chronic carder state being due to tolerance, selflimited acute hepatitis to effective and fulminant hepatitis to unrestrained anti-viral immune response. While there is evidence to support the first two hypotheses, few data are available in fulminant hepatitis, especially at

the tissue level. A 9-year old girt developed fulminant hepatitis B (HBsAg and IgM anti-HBc positive, HBV DNA negative, AST1550 IU/l, bilirubin 640 txmol/1, INR 3.7) and underwent emergency liver transplantation. The massive mononuclear cellular infiltrate observed in the explanted liver by conventional histology was analysed immunohistochemically on both frozen and formalin fixed sections for the following markers: CD3 (panT), CD4 (T-belper), CD8 (T-cytotoxic), CD22 (B lymphocytes), CD 14 and 68 (macrophages), CD45RA/RO (naive/committed cells), CD 56 (natural killer cells), CD161 (natural killer T cells), interferon-gamma and IL2 (type 1 T-cells), intedeukin 4 (type 2 T-cells), pefforin and granzyme B (effector molecules of cytolysis, present in CD8, NK and NKT cells). The vast majority of the infiltrating mononuclear cells expressed CD3, CD8, CD45RO, pefforin and granzyme B. Interferon-gamma, IL-2, macrophages and TNF positive ceils were also prominent. Cells of other lineages were rarer or undetectable. These data suggest that committed cytotoxic T cells with a type 1 phenotype, equipped with machinery of lysis mediate the massive hepatocyte destruction characteristic of fuhninant hepatitis B.

~ 7 - ~ INDUCING IMMUNOSUPRESSION WITH BASILIXlMAB IN LIVER TRANSPLANTATION Marco A. Olivera-Martinez 1, Alvaro Lopez 2, Juan Jose Plata 2, Erik Galindo 2, Carlos Chan.Nunez 2, Paulino Leal-Villalpando 3, Miguel A. Mercado-Diaz 2, Hector Orozco-Zepeda 2 . i Department of

Gastroenterology, lnstituto Nacional de Ciencias Medicas y Nutricion; 2Department of Surgery, lnstituto Nacional de Ciencias Medicas y Nutricion; 3Department of Critical Care Medicine, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico Aim: to report 7 patients receiving induction with basiliximab as immunosupression after liver transplantation in Mexico and compare them with a previously transplanted population using a different immunosupressive regime. Methods: we defined 2 groups: (A) N=8, patients transplanted before 1997 receiving cyclosporine (CSA), azathioprine (AZA) and prednisone (PDN); (B) N=7, patients transplanted between 1999 and 2001 receiving tacrolimus (TCR), PDN and basiliximab (20 mg on day 0 and 20 mg on day 5 post-transplant); both groups with at least 3 months survival, 2 serial liver biopsies and serial liver tests. Demographics, rejection history and histopathology are reported. Rejection was defined as abnormal GGT, AST and/or ALT in 2 serial determinations with typical histological findings (endotheliitis, lymphocytic portal inflammatory infiltrate and biliary epithelial damage). Results: Three month survival is 100% for both groups. Indications for liver transplantation are similar for groups A and B. Acute rejection episodes were present in 7/8 cases in group A (five patients presented 1 episode and 2 patients presented 2 episodes) and 0/7 in group B (p--0.001). Condusions: Basiliximab with TCR and PDN is a better induction immunosupressive regime that prevents the development of acute rejection in the early post-transplant period (3 months). Randomized multicenter trials are necessary to confirm these results.

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ALFA-IFN (N3) PLUS RIBAVIRIN TREATMENT IN HCV RECURRENCE AFTER LIVER TRANSPLANTATION (OLT)

Sara Pevere, Stefano Targhetta, Patrizia Boccagni, Giacomo Zanus, Dino Martines, Patrizia Burra, Umberto Cfllo, Remo Naccarato, Stefano Fagiuoli. Department of Surgical and Gastroenterological

Sciences, Padova, Italy Post-OLTx HCV recurrence is virtually universal but incidence and severity of graft disease are still controversial. Aim of this study was to evaluate efficacy and tolerabflity of natural (N3) alfa-IFN alone and in combination with Ribavirin in an open treatment protocol for OLTx recipients with HCV recurrent disease. Between 11/1990 and 6/2000 84 patients with HCV related ESLD were transplanted out of a total of 252 (33.3%). Thirty