Intrahepatic portal-systemic venous shunt in the adult. Case report and review of the literature

S86

Abstracts

Purpose: We examined the sensitivity of matrix metalloproteinase inhibitor (MMPI: marimastat) on HCC. Methods: MMPI was administered to experimentally induced HCC rats by diethylnitrosamine via alzet osmotic pump invested in the peritoneal cavity for 6 weeks. The administration was started at various time points including the initiation of DEN and 4, 6 and 12 weeks thereafter. The result was evaluated by macroscopic examination (red nodes: HCC) in hepatic vascular casts (red resin: hepatic artery, blue resin: portal vein) together with SEM, immunohistology (MMP–2, 9, MT1–MMP), zymograpy and northern blotting analyses. Furthermore, the effect of MMPI on tube formation was also examined in HUVEC (human umbical vascular endothelial cell) and rat sinusoid endothelial cell (HSEC) according to differed hepatitis viruses and expression modes of individual MMPs using liver biopsy samples and 30 HCC resected cases. Results: In the comparison at 12 weeks during carcinogenesis, the rate of decrease as high as 60 – 70% was observed in the maximum diameter as well as the number of red node in all MMPI treated groups examined. During carcinogenesis, these effects reached a peak at 4 – 10 weeks in all treated groups though no significant difference was evident at initiation of DEN and 6 weeks. In the treated group after 12 weeks, a tumor dormancy effect was observed. The results of immunohistology, zymography and northern blotting analyses also supported these findings mentioned above. In clinical cases, the expression coincidence of MMP–2 with MT1–MMP seemed to be important as a background factor of carcinogenesis. After carcinogenesis, a possible involvement of MMP–7, 9 was suggested in the infiltration. Because of its extensive expression, MT1–MMP seemed to have played as a key factor. The tube formation of HUVEC and HSEC was rated as HCV–HBV– ealthy sera in degree, showing the highest rate of suppression by MMPI for HCV. Conclusions: The sensitivity of MMPI being one of anti–angiogenic treatments was estimated to become evident around the time when the carcinogenic process, especially its fibrillation, began to appear to some extent. In the clinical cases as well, MMPI seemed possible to be applied for treating HCC (MMP–7, 9, MT1–MMP) and chemoprevention (MMP–2, MT1–MMP). MMPI may also exhibit its efficacy in the background of HCV. 261 N–ACETYLCYSTEINE IN NON–ACETAMINOPHEN INDUCED ACUTE LIVER FAILURE IN CHILDREN Sameer Gupta, M.D., Marla Gerrek, C.F.N.P., Steve Czinn, M.D., Christopher Siegel, M.D. and Samra S. Blanchard*. Pediatric Gastroenterology, University Hospitals of Cleveland, Cleveland, OH and Transplant Surgery, University Hospitals of Cleveland, Cleveland, OH. Purpose: Acute liver failure is a serious condition associated with poor prognosis. The morbidity and mortality are due to impairment in liver function as well as changes in systemic hemodynamics causing multi– organ failure. N–acetylcysteine has played an important role in preventing acetaminophen induced liver failure. Recent studies of N–acetylcysteine in adults with non–acetaminophen related fulminant liver failure have demonstrated beneficial effects on liver function, increased oxygen delivery to liver tissue, and improvements in clinical outcomes. Results: N–acetylcysteine was administered at presentation to 3 pediatric patients, aged 21 days, 8 years and 12 years, who presented with non– acetaminophen induced acute and sub–acute liver failure. The dose of N–acetylcysteine was equivalent to that used in acetaminophen toxicity. We also reviewed the charts of two patients at age of 6 years and 14 years with acute liver failure who did not receive N–acetylcysteine as a control group. Patients were followed for changes in clinical parameters (encephalopathy), coagulation factors, and outcome. Clinically, 2 of the patients who received N–acetylcysteine did not progress, and have fully recovered. The mean peak prothrombin time, serum factor V, aspartate aminotransferase and alaninetransferase levels all improved with administration of N–acetylcysteine. One patient still required transplantation, but she was hemodynamically stable without encephalopathy at the time of transplantation. Two patients who did not receive N–acetylcysteine developed Grade III–IV encephalopathy requiring liver transplantation. One of these patients

AJG – Vol. 97, No. 9, Suppl., 2002

expired at the time of transplantation surgery and the other was successfully transplantated. No side effects of the drug were noted. Conclusions: This study suggests that N–acetylcysteine administration may have a role in pediatric patients with acute or sub–acute liver failure regardless of the etiology. 262 FOOD ALLERGY WITH PARTIAL VILLOUS ATROPHY AFTER PEDIATRIC LIVER TRANSPLANTATION WITH TACROLIMUS IMMUNOSUPPRESSION Samra 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, University Hospitals of Cleveland, Cleveland, OH and Transplant Surgery, University Hospitals of Cleveland, Cleveland, OH. Purpose: This report reveals our experience with food allergy causing partial villous atrophy in pediatric liver transplant recipients receiving tacrolimus immunosuppression. Methods: We reviewed the charts of three pediatric liver transplant recipients who 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 18 months old, who presented with food allergies after liver transplantation. They were on tacrolimus and low dose of steroids when they presented with allergy symptoms. All three patients had heme–positive stools. They presented 15, 3 and 12 months after their transplantation. First two patients also had mild to moderate reactive airway disease, failure to thrive and vomiting as their presenting symptoms. None of the patients had eczema, hives or anaphylactic reaction. All three patients had normal serum IgE level, normal eosinophil count and negative endomysial antibody level.They all have varying classes of positive radioallergosorbent test measuring serum–specific Ig E and IgG for whey, casein, eggs and wheat. All three patients had partial villous atrophy in their biopsies. All the patients were put on strict elemental formula (Neocate plus) with elimination diet. The second patient was not compliant with diet causing low levels of tacrolimus level requiring dose increase with worsening of gastrointestinal symptoms. Conclusions: The specific risk factor for the development of food allergy seems to be the tacrolimus immunosuppression as there are no reports of food allergies in cyclosporine–immunosuppressed patients. It is also reported in animal studies that tacrolimus increases intestinal permeability which 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 poor absorption of immunosuppressive drugs that can put them risk of rejection. Strict elimination diet or change of immunosuppression is necessary in this group of patients. Further studies are necessary to determine the causal relationship between tacrolimus and food allergies. 263 INTRAHEPATIC PORTAL–SYSTEMIC VENOUS SHUNT IN THE ADULT. CASE REPORT AND REVIEW OF THE LITERATURE Christine Pocha, M.D., Mohammad M. Alsolaiman, M.D. and Benedict Maliakkal, M.D.*. Department of Medicine, Albany Medical Center, Albany, NY and Department of Gastroenterology, Albany Medical Center, Albany, NY. Purpose: Intrahepatic portal–systemic venous shunts are defined as communication between the portal and the systemic–venous circulation, measuring more than 1mm in diameter, and at least partially located inside the liver. This is a rare condition, and its cause is disputed. Type I with patent paraumbilical veins, located in the liver is commonly encountered in portal hypertension.

AJG – September, Suppl., 2002

Abstracts

Type II, III and IV are much less common. Such cases have been reported in only 47 publications in the entire French and English literature. Shunts may be congenital or acquired. This report describes a case of portal–systemic encephalopathy due to a spontaneous large– caliber portal– hepatic venous shunt in the right lobe of the liver confirmed by percutaneous transhepatic portography and hepatic venous angiogram. The treatment with coil embolization was successful, and hepatic encephalopathy resolved postoperatively with normalization of ammonia level. The etiology of the shunt was unclear. Given the age of the patient shunt was thought to be spontaneous. 264 IS GILBERT’S SYNDROME THE CAUSE OF JAUNDICE IN HYPERTROPHIC PYLORIC STENOSIS (HPS)? Omar Abdul–Rahman, M.D., Michael J. Nowicki, M.D.*, Dongping Shi, M.D., Phyllis R. Bishop, M.D., Paul H. Parker, M.D. and Warren L. May, Ph.D. Pediatric Gastroenterology and Nutrition, University of Mississippi Medical Center, Jackson, MS and Preventive Medicine, University of Mississippi Medical Center, Jackson, MS. Purpose: HPS is complicated by jaundice in 2% to 8% of infants, which may represent an early manifestation of GS. A mutation in the promoter region of the bilirubin uridine diphosphate glucuronyl transferase (B–UGT) gene is responsible for most cases of GS. Methods: Infants with HPS were identified retrospectively through a chart review, and prospectively at the time of surgery for the past 12 years. Data collected included: age at surgery; sex; race; degree of illness (determined by serum markers: Na, K, CO2, Cl, glucose, and venous pH). All jaundiced infants (total bilirubin ⬎ 1.3 mg/dl) were invited to participate; control subjects were matched for age, sex, race, and degree of illness. DNA, extracted from whole blood or cheek– brushings, was used for sequencing, as well aslabeled amplification, of the promoter region of the B–UGT gene. Results: 212 infants with HPS were identified; 29 (13.5%) were jaundiced. Overall, there was no difference between the 2 groups in age, gender, or race. There was no difference in markers for degree of illness except for CO2 being higher in jaundiced (29.0 ⫾ 6.5 mmol/L ) than non–jaundiced infants (26.0 ⫾ 4.9 mmol/L; p ⬍ 0.005). 11 subjects with jaundice and 15 controls were enrolled. No difference was seen in Na, CO2, Cl, glucose, or venous pH between the jaundiced and control subjects. Results of demographics and mutational analysis are found in the table. Demographics & mutational analysis in infants with HPS Age (wks)

Sex Race Breast (male) (white) fed

6/6

6/7

7/7

Jaundiced 5.3 ⫾ 1.6 72.7% 54.5% 18.1% 1 (9.0%) 7 (63.3%) 3 (27.7%) (n⫽11) Non–jaundiced 6.1 ⫾ 3.8 68.4% 63.2% 4 (26.6%) 9 (60%) 2 (13.3%) (n⫽15) 6/6 (wild–type), 6/7 (heterozygote), 7/7 (GS); expressed as # (%).

Conclusions: GS, not degree of illness, explains the occurrence of jaundice in some infants with HPS. The prevalence of GS in jaundiced infants with HPS (27.7%) is higher than in non–jaundiced infants (13.3%); however GS does not account for all jaundiced infants with HPS. Some patients with HPS and jaundice may have GS due to point mutations elsewhere in the B–UGT gene, although this was not tested for in our study . 265 P53 GENE AND MISMATCH REPAIR GENE MUTATION STATUS AND CLINICAL OUTCOME IN HEPATOCELLULAR CARCINOMA PATIENTS Masatugu Yano, M.D., Toshimasa Asahara, M.D.*, Yuko Hirai, Ph.D., Kiyohiro Hamatani, Ph.D. and Donald G. MacPhee, Ph.D. Department of Surgery II, Hiroshima University School of Medicine, Hiroshima, Japan and Department of Radiobiology, Radiation Effects Research Foundation, Hiroshima, Japan.

S87

Purpose: To investigate the correlation between p53 and mismatch repair gene mutation and long term outcome of HCC patients, we analyzed 83 patients for mutations in p53 a nd mismatch repair gene (hMSH2). Methods: The patients group consisted of 68 men and 15 women; ages 46 to 77. Samples were obtained by surgically curative resection. Genomic DNA was extracted with phenol– chloroform. Mutations in the p53 and mismatch repair gene were analyzed by the PCR–SSCP method and the direct sequencing method. And we used five microsatellite markers to evaluate the mismatch repair function. Results: Mutations of the hMSH2 gene were detected in 11 patients (13%), and mutations of the p53 gene were detected in 16 patients (19%). Only one mutation was observed in tumors less than 2 cm in diameter. There was a significant correlation between mutation and pathological factors of malignancy. The survival rate of patients with mutation–positive tumors was much poorer than those in patients with mutation–negative tumors. And 60% of cases with mutation–positive tumors exhibited microsatellite instability, whereas 20% of cases with the mutation–negative tumors had microsatellite instability. Intrahepatic metastasis was common recurrent pattern in mutation–positive patients. However the recurrent pattern in mutation–negative patients was mainly multicentric occurrence. Conclusions: Our data suggest that loss of p53 and mismatch repair function plays a large role in microsatellite induction in HCC. And our results also suggest that mutations in the p53 or mismatch repair gene may closely correlate with the survival and recurrent pattern of HCC patients.

266 PEGYLATED INTERFERON ALPHA 2B INDUCES LESS THYROID DYSFUNCTION THAN STANDARD INTERFERON ALPHA 2B IN THE TREATMENT OF CHRONIC HEPATITIS C Yashma Patel, M.D., Rajeev Chapalamadugu, M.D., Susan Ramdhaney, M.D., Robin Baradarian, M.D., Kadirawel Iswara, M.D.,FACG and Scott Tenner, M.D.,M.P.H.,FACG*. Gastroenterology, Maimonides Medical Center, Brooklyn, NY and State University of New York Health Sciences, Brooklyn, NY. Purpose: Chronic Hepatitis C is a common disorder affecting about 4 million people in the United States. Due to a higher efficacy in viral eradication, PEGylated Interferon is replacing standard interferon in the treatment of Chronic Hepatitis C. In order to determine if there were differences in the development of thyroid dysfunction in patients treated with either PEGylated interferon or standard interferon, the following study was undertaken. Methods: Patients being treated for chronic hepatitis C were prospectively followed for the development of thyroid dysfunction. Serum TSH levels were obtained on all patients at monthly intervals to determine thyroid function. Patients with abnormal TSH levels were temporarily discontinued from interferon until levels normalized. Twenty–three patients were treated with standard interferon alpha 2b (Intron A – 3 million units thrice weekly) and twenty–three patients were treated with PEGylated interferon alpha 2b (PEG Intron A 1.5 ug/kg weekly). Both groups of patients received ribavirin. Results: There were no significant differences between the two groups regarding age, gender, genotype, and pre–treatment TSH levels. Thyroid dysfunction, defined by an abnormal TSH, was seen in 12 patients (52%) treated with standard interferon and in 3 patients (13%) treated with PEGylated interferon (p⬍0.01). Two of the patients on standard interferon and none of the patients on PEGylated interferon were found to have recurrent abnormal TSH levels. None of the patients from either group were permanently discontinued from Hepatitis C treatment due to thyroid dysfunction. Persistent thyroid dysfunction leading to medical treatment was not seen in any of the patients following completion of Hepatitis C therapy. Conclusions: We conclude that thyroid dysfunction is more commonly seen in patients treated with standard interferon compared to PEGylated interferon. Our strategy of closely monitoring the serum TSH levels at monthly intervals and temporarily discontinuing interferon may lead to rapid normalization of thyroid function with less recurrence. This may