QS215. ANTI-THYMOCYTE GLOBULIN (ATG) ATTENU-ATED HEPATIC ISCHEMIA-REPERFUSTION (IR)INJURY IN MICE. Siddhartha Rath, Hosein Shokouh-amiri, Xinje Mu, Kevin Boykin, Richard Turnage, Gazi Zi-bari; LSU Health Sciences Center, Shreveport, LA

Purpose: Hepatic ischemia-reperfusion (IR) injury is characterizedby both a local and systemic inflammatory process. We have previ-ously shown that: a) reperfusion of ischemic hepatic tissue causesneutrophil adhesion and tissue injury; b) modulation of neutrophiladhesion attenuates hepatocyte injury. Potential abrogation of he-patic IR injury may prevent primary non-function of transplantedorgans, increasing log-term graft survival by limiting the initialpro-inflammatory phenotype. We hypothesized that imunomodula-tion with anti-thymocyte globulin (ATG) would prevent reperfusion-induced liver injury by abolishing neutrophil-mediated tissue injury.Methods: Male C57BL6/ mice were used for all experiments anddivided into the following groups (n�8): sham, IR, sham �ATG(20mg/kg), and IR � ATG(20mg/kg). IR groups underwentclamping of the vascular pedicle to the left lateral hepatic lobe for 45minutes and reperfusion for one hour. In the groups receiving ATG,this was administered at the time of reperfusion. Following reperfu-sion, rhodamine was administered intravenously and leukocyte dy-namics were directly visualized using intra-vital microscopy. In sep-arate experiments, following reperfusion, tissue was sent forhistology and serum was sent for hepatocellular enzyme assay. Re-sults: Following IR, we observed a significant decrease in all mea-sured parameters (rolling, saltation and aggregation) in the ATGgroup. Additionally, there was a significant attenuation of hepato-cellular injury (decreased AST.ALT) in the ATG group. Histologicalcomparison between sham and ATG groups approached, however,did not reach significance. Conclusion: From these data, we con-cluded that ATG at a physiologic dose attenuates hepatic IR injuryby contributing to inhibition of leukocyte activation and/or adhesionin the hepatic microcirculation.

QS216. ACTIVATION OF P38-MAPK IN BRAIN MICROVES-SELS OF FULMINANT HEPATIC FAILURE MICE.Florence Chen, Justin H. Nguyen; Mayo Clinic College ofMedicine, Jacksonville, FL

Brain edema, resulted from increased permeability across the blood-brain barrier (BBB), is a lethal complication in fulminant hepaticfailure (FHF). The pathogenesis of brain edema in FHF remainsincompletely understood and therapeutic options are limited. Wehypothesized that mitogen activated protein kinases (MAPK) play arole in the increased BBB permeability in FHF.FHF is experimentally induced with azoxymethane in a reproduc-ible and well characterized model in mice. In our previous study(J Hepatol 2006;44:1105), we have shown an increased BBB per-meability in the comatose, but not in the precoma FHF mice. Inthis study, brain microvessels were isolated from mice at precomaand comatose stages, and from the normal control mice. Microves-sel lysates were prepared and analyzed by western blotting forphospho-p38 and p38 using anti-phospho- p38 MAP kinase(Thr180 /Tyr182; Santa Cruz, CA, USA), anti-p38 MAP kinase(Cell Signaling). The ratio of phospho-p38:p38 at each encepha-lopathy stage was determined. Values are expressed as themeans�SEM with t-test. We found that the phosphorylated p38MAPK was significantly increased in precoma FHF mice, 40%above the normal control mice, Figure 1 (N�10, * P�0.05). Nodifference was seen in the comatose FHF mice as compared to thecontrol animals.In conclusion, p38 MAPK is significantly activated in the precomastage preceding the onset of the increased BBB permeability inFHF. These findings suggest a potential role of p38 MAPK in thedevelopment of brain edema in FHF and p38 MAPK may be anuseful therapeutic target.

QS217. CLINICAL AND PATHOLOGICAL ANALYSIS OFHEPATOCELLULAR CARCINOMA ORIGINATEDFROM THE LIVER WITHOUT VIRAL HEPATITIS.Keishi Sugimachi, Akinobu Taketomi, Seiji Maruyama, Yoi-chi Yamashita, Tomoharu Yoshizumi, Yuji Soejima, Yoshi-hiko Maehara; Kyushu University, Fukuoka, Japan

In Japan, most hepatocellular carcinoma (HCC) occurs in the liverassociated with either viral hepatitis type B or type C. Recently, thenumber of HCC patients without concomitant viral hepatitis (NVH-HCC) has been increasing. Non alcoholic steatohepatitis (NASH) isthought to be one of the origins of hepatocarcinogenesis, but themechanism and relevance of hepatocarcinogenesis and hepatic ste-atosis has not been clear. The large scale clinical study of HCC withNASH has also not been reported. In this study, we report theclinicopathological features of NVH-HCC, and examined the signif-icance of the pathological steatosis and fibrosis in NVH-HCC.Data for 362 patients with HCC who underwent first hepatectomyfrom 1995 to 2005 were collected from the charts. These cases werecategorized in 4 groups; 59 cases without viral hepatitis (NVH-HCC),64 cases with hepatitis type B (B-HCC), 225 cases with hepatitis typeC (C-HCC), and 14 cases with both hepatitis type B and C. Theclinical outcomes of these cases were retrospectively reviewed.[1] The average age of NVH-HCC was significantly higher than thoseof B-HCC and C-HCC (p�0.01). 39.2% of NVH-HCC cases had con-comitant diabetes mellitus, which was significantly higher thoseB-HCC and C-HCC. The body mass index of NVH-HCC was alsosignificantly higher than B-HCC and C-HCC (p�0.03). The hepaticfunction and reserve were compared among 3 groups. NVH-HCCcases showed higher serum albumin level and prothrombin time, andlower serum transaminase level and indocyanine green retentionrate at 15 minutes compared to B-HCC and C-HCC. The cumulativesurvival rates were not different among 3 groups, but the disease-free survival rate of the NVH-HCC group was higher than theC-HCC group. [2] Pathological examination of non-cancerous tissueof the liver in NVH-HCC cases was done. Microscopic steatosis(�10%) was seen in 18 cases (31.6%). Among these, 8 cases (14.0%)showed concomitant lobular hepatitis, which was diagnosed as ste-atohepatitis. Five of 8 cases had a history of daily alcohol consump-tion, so that 3 cases (5.3%) were finally diagnosed as NASH. Two of3 cases had lifestyle related diseases (diabetes and hypertension).Severe liver fibrosis was seen 2 of 3 cases.[Summary] NVH-HCC cases had well preserved hepatic functionand reserve compared to B-HCC and C-HCC cases. NVH-HCC cases

353ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS