75 SELECTIVE SPLANC~NIC HYPEREMIC EFFECTS OF GLUCAGON IN PATIENTS WITH WELL

COMPENSATED CIRRHOSIS S.S. Lee, R. Moreau, A. Hadensue~ R. Cerinl, A. Koshy, P. Garnier, D. Lebrec INSERM U24, HSpital Beaujon, Clichy and the Fondation de Recherche en Hormonologie, Fresnes, France

To investigate the hypothesis that glucagon mediates the splanchnic hyperemia of portal hypertension, we studied its circulatory effects in cirrhotic patients. Since serum glucagon levels are elevated according to the stage of liver disease, patients were grouped into those with good liver function (Pugh class A, n=8) and poorer function (class B and C, n=ll). Glucagon was infused at I0 ng/kg.min, then at 20 ng/kg.min, for 20 min each. Cardiac output, arterial pressure, systemic vascular resistance, hepatic venous pressure gradient, hepatic and renal blood flow were measured basally and during the second glucagon infusion. Serum glucagon, catecholamines and azygos blood flow were measured basally and during both infusions.

Basal glucagon levels were different in the 2 groups but rose similarly during the infusions: group A, 74±15, 1081±319, 2324±527 pg/ml and group BC, 380±136, 1098±178, 2291±254 pg/ml (mean±SE). Basal noradrenaline levels also differed between the 2 groups but did not change in either group. Azygos blood flow increased significantly only in group A: 0.32±0.04, 0.40±0.07, 0.48±0.08 I/min; group BC, 0.54±0.08, 0.54±0.07, 0.53±0.07 I/min. No other measurement changed in either group.

We conclude that: I) a moderately supraphysiologic dose of glucagon selectively increases portal collateral blood flow by a non-sympathetic mechanism, only in well- compensated cirrhotic patients. The desensitization in poorly-compensated patients with higher glucagon levels may reflect down-regulation. 2) These results support the contention that glucagon may mediate the splanchnic hyperemia, at least in the initial stages. 3) Measurement of azygos blood flow may be the most sensitive technique to detect splanchnic circulatory changes after some vasoactive agents.

76 SOLUBLE INTERLEUKIN 2 RECEPTORS IN SERUM OF CHILDREN WITH AUTO- IMMUNE CHRONIC ACTIVE HEPATITIS [aCAH]

A.Lobo-Yeo, G.Mieli-Ver$ani, AP Mowat, D.Vergani. Dept. of Child Health and Immunology, King's College Hospital, London. UK

Increased numbers of activated T lymphocyte§ expressing Interleukin 2 receptors(IL2R)are found in patients with uncontrolled autoimmune chronic active hepatitis [aCAH]. A soluble form of IL2R has been recently described. Two monoclonal antibodies directed against non- overlapping epitopes(anti Tac and 7G7 antibody) on the human IL2R were used in an ELISA to measure soluble IL2R in the serum of 16 children with autoimmune CAH, 7 with Wilson's disease (WD), 9 with alpha-l-ant±trypsin deficiency [~I-ATD) and 15 healthy age matched controls. Soluble IL2R concentration was significantly higher in patients with aCAH than in healthy controls [mean ± sem 475 ± 75 U/ml, 145 ± 8U/ml respectively, p <0.01). Eleven patients who had active disease had levels of soluble IL2R significantly higher(590±89U/ml) than the five cases with inactive disease (220 ± 36U/ml: p < 0.01). No difference with controls was found in the patients with WD or $1ATD.

Percentage of surface IL2R positive T cells as detected by immunofluorescence was significantly higher in the patients with aCAH (11.8 ± 1%) than in the controls(0.2 ± 0.1%, p < O.OO1). A significant positive correlation was observed between concentrations of soluble IL2R and the percentage of T cells expressing IL2 receptors( Rs=O.67,p <O.O01).

The release of soluble IL2R appears to be a marker of T lymphocyte activation and its measurement in serum could provide a practical and rapid indicator of disease activity in patients with aCAH.

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