Purpose: We examined the sensitivity of matrix metalloproteinase inhib-itor (MMPI: marimastat) on HCC.Methods: MMPI was administered to experimentally induced HCC rats bydiethylnitrosamine via alzet osmotic pump invested in the peritoneal cavityfor 6 weeks. The administration was started at various time points includingthe initiation of DEN and 4, 6 and 12 weeks thereafter. The result wasevaluated by macroscopic examination (red nodes: HCC) in hepatic vas-cular casts (red resin: hepatic artery, blue resin: portal vein) together withSEM, immunohistology (MMP–2, 9, MT1–MMP), zymograpy and north-ern blotting analyses. Furthermore, the effect of MMPI on tube formationwas also examined in HUVEC (human umbical vascular endothelial cell)and rat sinusoid endothelial cell (HSEC) according to differed hepatitisviruses and expression modes of individual MMPs using liver biopsysamples and 30 HCC resected cases.Results: In the comparison at 12 weeks during carcinogenesis, the rate ofdecrease as high as 60 – 70% was observed in the maximum diameter aswell as the number of red node in all MMPI treated groups examined.During carcinogenesis, these effects reached a peak at 4 – 10 weeks in alltreated groups though no significant difference was evident at initiation ofDEN and 6 weeks. In the treated group after 12 weeks, a tumor dormancyeffect was observed. The results of immunohistology, zymography andnorthern blotting analyses also supported these findings mentioned above.In clinical cases, the expression coincidence of MMP–2 with MT1–MMPseemed to be important as a background factor of carcinogenesis. Aftercarcinogenesis, a possible involvement of MMP–7, 9 was suggested in theinfiltration. Because of its extensive expression, MT1–MMP seemed tohave played as a key factor. The tube formation of HUVEC and HSEC wasrated as HCV–HBV–ealthy sera in degree, showing the highest rate ofsuppression by MMPI for HCV.Conclusions: The sensitivity of MMPI being one of anti–angiogenic treat-ments was estimated to become evident around the time when the carci-nogenic process, especially its fibrillation, began to appear to some extent.In the clinical cases as well, MMPI seemed possible to be applied fortreating HCC (MMP–7, 9, MT1–MMP) and chemoprevention (MMP–2,MT1–MMP). MMPI may also exhibit its efficacy in the background of HCV.

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N–ACETYLCYSTEINE IN NON–ACETAMINOPHEN INDUCEDACUTE LIVER FAILURE IN CHILDRENSameer Gupta, M.D., Marla Gerrek, C.F.N.P., Steve Czinn, M.D.,Christopher Siegel, M.D. and Samra S. Blanchard*. PediatricGastroenterology, University Hospitals of Cleveland, Cleveland, OH andTransplant Surgery, University Hospitals of Cleveland, Cleveland, OH.

Purpose: Acute liver failure is a serious condition associated with poorprognosis. The morbidity and mortality are due to impairment in liverfunction as well as changes in systemic hemodynamics causing multi–organ failure. N–acetylcysteine has played an important role in preventingacetaminophen induced liver failure. Recent studies of N–acetylcysteine inadults with non–acetaminophen related fulminant liver failure have dem-onstrated beneficial effects on liver function, increased oxygen delivery toliver tissue, and improvements in clinical outcomes.Results: N–acetylcysteine was administered at presentation to 3 pediatricpatients, aged 21 days, 8 years and 12 years, who presented with non–acetaminophen induced acute and sub–acute liver failure. The dose ofN–acetylcysteine was equivalent to that used in acetaminophen toxicity.We also reviewed the charts of two patients at age of 6 years and 14 yearswith acute liver failure who did not receive N–acetylcysteine as a controlgroup. Patients were followed for changes in clinical parameters (enceph-alopathy), coagulation factors, and outcome. Clinically, 2 of the patientswho received N–acetylcysteine did not progress, and have fully recovered.The mean peak prothrombin time, serum factor V, aspartate aminotrans-ferase and alaninetransferase levels all improved with administration ofN–acetylcysteine. One patient still required transplantation, but she washemodynamically stable without encephalopathy at the time of transplan-tation. Two patients who did not receive N–acetylcysteine developed GradeIII–IV encephalopathy requiring liver transplantation. One of these patients

expired at the time of transplantation surgery and the other was successfullytransplantated. No side effects of the drug were noted.Conclusions: This study suggests that N–acetylcysteine administrationmay have a role in pediatric patients with acute or sub–acute liver failureregardless of the etiology.

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FOOD ALLERGY WITH PARTIAL VILLOUS ATROPHYAFTER PEDIATRIC LIVER TRANSPLANTATION WITHTACROLIMUS IMMUNOSUPPRESSIONSamra S. Blanchard, M.D., Marla Gerrek, C.F.N.P., Steve Czinn, M.D.,Gisela Chelimsky, M.D., David Seaman, M.D., Christopher Siegel, M.D.and Judy Splawski, M.D.*. Pediatric Gastroenterology, UniversityHospitals of Cleveland, Cleveland, OH and Transplant Surgery,University Hospitals of Cleveland, Cleveland, OH.

Purpose: This report reveals our experience with food allergy causingpartial villous atrophy in pediatric liver transplant recipients receivingtacrolimus immunosuppression.Methods: We reviewed the charts of three pediatric liver transplant recipientswho were diagnosed with food allergy noting the onset and type of symptoms,histological presentation and treatment received for their symptoms.Results: We report three patients, 6years, two and a half years and 18months old, who presented with food allergies after liver transplantation.They were on tacrolimus and low dose of steroids when they presented withallergy symptoms. All three patients had heme–positive stools. They pre-sented 15, 3 and 12 months after their transplantation. First two patientsalso had mild to moderate reactive airway disease, failure to thrive andvomiting as their presenting symptoms. None of the patients had eczema,hives or anaphylactic reaction. All three patients had normal serum IgElevel, normal eosinophil count and negative endomysial antibody lev-el.They all have varying classes of positive radioallergosorbent test mea-suring serum–specific Ig E and IgG for whey, casein, eggs and wheat. Allthree patients had partial villous atrophy in their biopsies. All the patientswere put on strict elemental formula (Neocate plus) with elimination diet.The second patient was not compliant with diet causing low levels oftacrolimus level requiring dose increase with worsening of gastrointestinalsymptoms.Conclusions: The specific risk factor for the development of food allergyseems to be the tacrolimus immunosuppression as there are no reports offood allergies in cyclosporine–immunosuppressed patients. It is also re-ported in animal studies that tacrolimus increases intestinal permeabilitywhich may be predisposing factor for food allergies.

Allergic reaction to tacrolimus is not necessarily Ig E mediated.Endoscopic biopsies should be obtained to assess the duodenal histology

because partial villous atrophy can cause malabsorption including poorabsorption of immunosuppressive drugs that can put them risk of rejection.Strict elimination diet or change of immunosuppression is necessary in thisgroup of patients.

Further studies are necessary to determine the causal relationship be-tween tacrolimus and food allergies.

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INTRAHEPATIC PORTAL–SYSTEMIC VENOUS SHUNT INTHE ADULT. CASE REPORT AND REVIEW OF THELITERATUREChristine Pocha, M.D., Mohammad M. Alsolaiman, M.D. and BenedictMaliakkal, M.D.*. Department of Medicine, Albany Medical Center,Albany, NY and Department of Gastroenterology, Albany MedicalCenter, Albany, NY.

Purpose: Intrahepatic portal–systemic venous shunts are defined as com-munication between the portal and the systemic–venous circulation, mea-suring more than 1mm in diameter, and at least partially located inside theliver. This is a rare condition, and its cause is disputed.

Type I with patent paraumbilical veins, located in the liver is commonlyencountered in portal hypertension.

S86 Abstracts AJG – Vol. 97, No. 9, Suppl., 2002