4 8 2 A A A S L D A B S T R A C T S HEPATOLOGY October 1995

1501 HEMODYNAMIC EFFECTS OF OCTREOTIDE IN PATIENTS WITH CIRRHOSIS AND PORTAL HYPERTENSION.

L. Ruiz del Arbol. C. Aroeena. A. Monescillo, C. De la Serna, F. Bermeio. C. Martin de Ar~,ila. V. Defar~es. T. Perez, A. Garcfa Plaza. Liver Hemodynamic Unit. Gastroenterology Department. Hospital Ram6n y Cajal, Madrid, Spain.

The study was aimed at investigating the systemic and splachnic effects of Oetreotide (OCT) in 20 cirrhotics after an oesophageal variceal bleeding episode. Patients were double-blind randomized to receive OCT (50/@ i.v. bolus + 50#g/h i.v. infusion; n=10) or placebo (saline 0.9% n= 10). Variceal pressure (VP)*, cardiac output (CO), hepatic venous pressure gradient (HPGV), mean arterial pressure (MAP), and heart rate (HR) were measured before and 2", 5', 15", 30 and 60 min after bolus administration. Hepatic biood flow (ICG) was estimated before and 30 min following bolus infusion. There were no differences in clinical and hemodynamic baseline data in both groups. Placebo did not produce any significant hemodynamic change. OCT caused a maximum reduction in V P a t 5 min (from 20.0 + 2.1 to 17.0 + 2.1mmHg, -16.4%, p<0.01). This effect persisted at 15 min (17.6 + 2.7mmHg, -12.9%, p<0.01). HVPG significantly decreased at 2 min (from 17.1 _ 4.8 to 14.6 + 4.3 mmHg, -15.2%, p<0.O5) and at 5 min (14.9 + 4.1 mm Hg,-12.8% p < 0.01). This reduction persisted at 30 and 60 min (15.2 + 4.6 mmHg, -11.1%, p<0.01; 15.9 + 4.4 mm Hg,-7.8%). Hepatic blood flow decreased 12% at 30 min. The maximum systemic effect was at 2 min (HR:-21%; MAP:+16%; CO:-14%, p<0.05). This study shows that OCT i.v. administration produces a marked and inmediate decrease in VP and HVPG (bolus effect), that persists during continuos OCT i.v. infusion, though less intense. These results suggest that OCT i.v. could be a useful treatment in oesopbageal variceal bleeding.

1502 ALLOGRAFT REJECTION AND LACK OF CORRELATION WITH LOW HEPATIC-TISSUE CYCLOSPORINE CONCENTRATIONS. VK Rust~i. VK Ovloe. P Kimball*. Transplant Center, Fairfax Hospital, Falls Church, VA and *Transplant Immunology Laboratory, Medical College of Virginia, Richmond, VA.

Cyclosporine (CsA) is thought to prevent cellular rejection by selectively inhibiting production of interleukin-2 by T-helper cells. This study examined possible differences in tissue concentrations of cyclosporine and occurrence of rejection post-orthotopic liver transplantation (OLTx).

Liver biopsies from 13 OLTx patients done on the seventh postoperative day were utilized. Specimens were digested with 250 pl of collagenase solution, vortexed and incubated at 37°C for 24 hours. Samples were sonicated, centrifuged at 1400 g and CsA levels obtained by TDX.

No Rejection (n=6) Rejection (n=7) p=0.72

2140.9 _+ 1088.9 1698.3 + 432.0

Hepatic-tissue CsA concentrations showed no correlation with early cellular rejection after orthotopic liver transplantation. Larger sample size would al low this to be stated more convincingly. The role of CsA metabolites measured by TDX versus CsA measured by HPLC is being explored.

1503 RELATIONS AMONG HCV GENOTYPE AND SEROTYPE PATTERNS AND ROUTE, TIME AND OUTCOME OF INFECTIONS IN PATIENTS FROM THE SAME GEOGRAPHIC AREA. R Sacco 2, A Randone, D Fliohman, M Gallo, A Scaraaoi 2, F Bonino, O Schiraldi 2 and MR Brunetto Dept. of Gastreenterel. Molinette Hosp.Todno, 2 Clinica Medica II, Istituto di Clinica Medica e Malattie Infettive, Bari, Italy.

The analysis of HCV genotypes (Inno Lipa HCV, Innogenetics-Nuclear Laser, Milano) and anti-HCV serotypes (HCV Serotyping, Murex, Roma) allowed us to study whether these virologic features are associated with route, duration and outcome of HCV infection. We studied 80 anti-HCV positive (ELISA and immunoblotting) patients who were attended in a single hospital center and originated from a restricted geographic area. Twenty consecutive haemophiliacs (all males, median age 36 y., range 15-53 y.) with persistently elevated ALT serum levels and 10-20 years of disease history but without ultrasound signs of portal hypertension were matched for sex, age and disease features with 20 non haemophiliac patients (with CAH at histology). Twenty patients with hepatocellular carcinoma (HCC) (19 males and 1 female, median age 65 y., range 52-80 y.) and disease history of more than 20 y. were matched with 20 patients with cirrhosis but without HCC. HCV genotypes according to Simmond's classification were la, lb, 2a, 3 and 4. Type 1 HCVs were detected in 50% of haemophiliacs and in 60% of CAH, HCC and cirrhotic patients respectively. Type 2a HCV was found in 5%, 10% and 30% of haemophiliacs, CAH patients and HCC or cirrhotic patients respectively. Type 3 HCV was present in 35% of haemophiliacs but in none of CAH patients and in only 5% of patients with HCC or cirrhosis (p< 0.05). Type 4 HCV was detected in less than 5% of cases without significant differences among the patients' groups. A high level of correlation was present between HCV genotypes and serotypes. Type lb HCV appeared more frequently associated with HCC. Our findings suggest that HCVs, type 1 and 2 have always been the prevalent viruses in this restricted geographic area since they are consistent with data reported in recent HCV infections in non risk groups. The higher prevalence of genotype 3 in haemophiliacs who were infected by imported clotting factors more than 10 years ago is similar to the higher frequency of this genotype infection in young drug addicts. A possible explanation for the restriction of HCV 3 infection in risk groups with both past and recent infections is that the transmission efficiency of HCV 1 and 2 is higher than that of HCV 3 in community aquired infections. Therefore HCV 3 transmission might be significantly influenced by the size of infectious inocula.

1504 VASCULAR AND DISTRIBUTION CHANGES DURING AND AFTER LIVER REGENERATION: A MICROSCOPIC AND MULTIPLE INDICATOR DILUTION (MID) STUDY. FM Sadeghi', S Huling ~, AL Jones # and KS Pang +,*. FacUlty of Pharmacy + and Department of Chemical Engineering & Applied Chemistry*, University of Toronto, Canada, and the V.A. Medical Center ~, University of California, San Francisco, U.S.A.

Changes associated with 70 % partial hepatectomy (PH) of the rat liver were examined in tissue sections under light microscopy. Projected images computerized with VIDAS R revealed greater frequencies .(2.4) and increased area ratios (0.05) of vascular to total (tissue+vasci~lar) regions on Day 1 after PH; these decreased on Day 3, rebounded on Days 7 and 14 (2.0 and 0.03, respectively), and approached values for the shams. Values for Day 1 were significantly greater than those for Day 14, inferring a significant increase of the vasculature on Day 1 after PH. The size of the hepatic vascular areas, however, remained constant throughout regeneration. In parallel studies, liver perfusion (12 ml/min) was carded out with PH rats on Days 1, 3, 7, 14, and sham operated animals. When multiple, noneliminated reference indicators (SICr- RBC, lz~I-albumin, [14C]sucrose and 3H20 ) were injected as a bolus dose into the portal vein, outflow dilution profiles that are characteristic of flow-limited distribution, were obtained. The accessible cellular water was unchanged throughout regeneration. By contrast, the sinusoidal blood volume and total albumin and sucrose distribution spaces were greatest for Day 1, followed by Days 3, 7 and 14. The increases, excepting the sinusoidal blood volume for Day 1, were accounted for solely on the basis of the perfusion rate (flow/g) alone. The composite fmdings highlighted an increased vascular space immediately following PH (Day 1), but this rapidly dissipated with continued regeneration of the liver.