Al172 AASLD ABSTRACTS GASTROENTEROLOGY, VoI. IO8, No. 4

THE VALUE OF TRANSJUGULAR INTRAHEPATIC PORTOS¥STEMIC STENT-SHUNT (TIPSS) ON HYPERSPLENISM IN CIRRHOTIC PATIENTS. N. Simsek. A. Besim, F. Balksnci, S. Cevikce, G. Oksuzoglu, H.Telatar. Department of Gastroenterology, and Radiology, Hacettepe University Medical School, Ankara, Turkey.

TIPSS is a promising innovation for management of variceal bleeding, and intractable ascites. The therapy of hypersplenism in cirrhosis is splenectomy. The effects of TIPSS on hypersplenism in cirrhotic patients has not ben evaluated in detail. sixteen patientsunderwent TIPSS procedure at our institution. Two of them have hypersplenism and variceal bleeding. But one additional patient had TIPSS only for the treatment of hypersplenism. A 27 years old male with postnecrotic cirrhosis presented with the findings of hypersplenism including WBC of 900, and platelet of 20 000 without any other complication of cirrhosis. After TIPSS placement WBC count increased up to 2000-5000 and mild encephalopathy responded to the medical therapy. One year later his WBC was 1000, and portography showed intimal hyperplasia inthe stent. WBC increased up to 4000 after second stent placement into the first one. WBC count showed very close correlation with the stent patency in all three patients with hypersplenism. CONCLUSIONS; TIPSS is an alternative therapeutic option in the treatment of hypersplenism in cirrhosis. WBC count should be helpful for the following shunt patency in these patients. Further controlled studies should bedone in larger patients population.

• HETEROZYGOUS ALPHA-I-ANTITRYPSIN (Het-AAT) OF Z PHENO- TYPE: A RISK FACTOR FOR LIVER D~SEASE (LD). H Sinqh, WD Carey and RJ Tuthill, Departments of Gastroenterology and Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, Ohio Objective: The association between LD and Het-AAT de- ficiency of the Z phenotype remains controversial and may vary in different parts of the world. Most reported North American series are small. Utilizing our large patient database we undertook this study to determine the prevalence of otherwise unexplained LD in the US in Het-AAT Z alleles, compared with Het-AAT with S allele who served as controls. Methods: Retrospective study of medical records of Het-AAT patients seen at a tertiary care referral center between 1983 and 1993. The incidence of unexplained LD in patients Het-AAT (Z allele) was compared to that of controls. Results: Sixty Het-AAT patients were identified. Of these 41 had sufficient clincal and laboratory information to be included. Group A included 28 (MZ and SZ). Group B in- ;cluded 13 MS patients. In Group A, (mean age: 58) 21 of 28 (75%) had LD. Of these 21, 9 (43%) had no other identified clinical or serological risk factor for LD. Three had alcoholic LD, 1 each had hepatitis B and C, and 3 had drug induced LD (methotrexate, INH, amiodarone). Another 4 (19%) had unexplained cirrhosis but hepatitis C could not be excluded. In Group B (mean age: 53), 6 of 13 (46%) had LD, but each had a predisposing factor other than AAT heterozygous S al- lele for LD (3 alcoholic LD, 1 hepatitis C, 1 hemochromatosis and autoimmune CAH, respectively). The presence of otherwise unexplained LD in patients with MZ or SZ was significantly more likely than in con- trols (MS), p=0.006, Fisher exact. Conclusion: (I) At least 40% of patients with MZ and SZ AA~T ~ phenotypes with LD had no other explanation for their LD. (2) These patients typically manifest LD after age 50. (3) The same genetic or environmental factors which predis- pose the homozygous (ZZ) AAT patients to develop LD may play a role in some Het-AAT Z patients.(4) Patients with unexplained LD should be evaluated for homozygote and heterozygote AAT deficiency.

• HEPATITIS A VACCINE: AN ACCELERATED DOSE SCHEDULE. MH Sjoqren, P Pittman, R La Chance, D Hack, R Makuch, A See, P Macarthy. USAMRIID, Ft. Detrick, MD, Walter Reed Army Medical Center, Washington DC, Walter Reed Army Inst. of Research, Washington, DC.

In humans, hepatitis A vaccine has been shown to be safe, immunogenic and protective against infection with hepatitis A virus (HAV). However, usual dose schedules (0, 1 and 6 or 12 months) are not suitable for individuals who need rapid protection, such as travelers to endemic areas. The purpose of the study was to observe if an accelerated schedule was acceptable in terms of side effects and anti- HAV response when compared to established dose administration. In this randomized, placebo-controlled study, l,051 volunteers were assigned to 2 groups. Group A received the accelerated schedule of 1 ml HAV vaccine in each deltoid muscle on day 0 and 1.0 ml of placebo into one deltoid muscle on day 30. Group B received 1.0 ml HAV vaccine in one deltoid and 1.0 ml placebo in the other deltoid on day O, and 1.0 ml HAV vaccine in one deltoid on day 30. Both groups had anti- HAV determination at 12 months, followed by a booster dose of HAV vaccine, 1.0 ml in a deltoid muscle. A cohort of volunteers were available for anti-HAV determination 30 days after the booster dose. HAV vaccine was HAVRIX (SmithKline Beecham, 720 EU/ml). Anti-HAV was tested by quantitative ELISA, positive anti-HAY > 20 mlU/ml,

Group A Group B n = "p" n= 526 525

anti-HAV (GMT) at 23.3 mlU/ml 33.7 mlU/ml ns 12 months

2005mlU/ml 2553mlU/ml 0.053 anti-HAY (GMT) at 13 months

The local and systemic side effects were minimal and similar in both groups. Except for local pain at the site of vaccine injection when compared to placebo (18% vs 5%, respectively, p< 0,001). In summary, both groups had similar anti-FIAV response to HAV vaccine. After the booster dose, anti-HAY response was brisk and with a significant increase in titer. In conclusion, the data suggest that the accelerated schedule is sac/ee and provides similar protection to the multiple dose schedule. This could result in a significant advance in terms of quick prevention against HAV infection.

CRITICAL ROLE OF PHOSPHATIDYLINOSITOL 3-KINASE IN INTRACELLULAR TRANSPORT AND EXOCYTOSIS. A__~. Slomianv. P. Nowak and B.L. Slomiany. Res. Ctr., UMDNJ, Newark, NJ 07103.

Activation and autophosphorylation of epidermal growth factor (EGF) receptor has been correlated with cellular signaling, one of which is expressed in the interaction of phosphatidylinositol 3-kinase (PI3K) with the receptor, but the outcome of this interaction is still unknown. To determine whether PI3K detected on Golgi transport vesicles is involved in the process, the vesicles attachment to cytoskeleton w~s investigated. The Golgi vesicles labeled with [~H]inositol and [3H]arachidonic acid, and the unlabeled cytoskeleton were isolated from rat hepatocytes. The attachment of transport vesicles to EGF-activated cytoskeleton was studied with the vesicles containing p85 PI3K subunit, in the presence of 100nM wortmannin inhibitor, after preincubation of cytoskeleton with cytosol, and with vesicles depleted of p85 PI3K subunit. The association of Golgi transport vesicles with cytoskeleton was observed only when p85 PI3K subunit was present on the vesicles and PI3K was active. In the presence of wortmannin, after preincubation of the cytoskeleton with cytosol, or after stripping p85 PI3K from the vesicles, the association of the Golgi vesicles with cytoskeleton was not observed, and the radioactive material separated from cytoskeleton fraction. Immunostaining of p85 revealed that preincubation of cytoskeleton with cytosol leads to the interaction of cytosolic P85 PI3K subunit with EGF receptor, and thus blocking the sites of the Golgi vesicles attachment. The study shows that PI3K is essential for the attachment of Golgi transport vesicles to EGF activated cytoskeleton. Supported by NIH, NIAAA grant AA05858-13.