Posters / International Hepatology Communications 3 Suppl. (1995) $37-$169 SI 11

P - 2 9 7 S T U D y OF THE CEREBRAL BLOOD FLOW BY 12sI-IMP SPECT DURING INTERFERON THERAPY FOR CHRONIC HEPATITIS C PATIENTS M.Sasaki, M.Sata, H.Suzuki, S.Murashima, I.Miyajima, Y.Uchimura, F.Akiyoshi, K.Fuknizumi, T.Ide, Y.Yamakawa, S.Noguchi, K.Tanikawa, M.Ishibashi l), M.Uchimura z) I.Nakamura 2). 2nd Dept. of Medicine, Dept. of Radiology 1), Dept. of Psychiatric z), Kmume University School of Medicine, Kurume, Japan. Purpose: Considering the possibility that changes in the cerebral blood flow are involved in neurop-sychologic symptoms induced by IFN administration, we studiedthe cerebral blood flow after IFN administration by single photon emissiolycomputed tomography (SPECT). Sub,iects and Methods: The subjeets'/were 11 patients (6 males and5 females) with chronic hepatitis C. IFN- a , IFN a 2a, IFN a 2b was administered at 6 , 9 and 10 million units daily for the first 2-4 weeks and3 times a week for the following 6 months, respectively. IFN B was administered at 6 million units daily for6 weeks. 123I-IMP (222 MBq) was administered and SPECT was executed before and 6-8 weeks after the beginning of IFN administration. All subjects underwent an interview and personality tests by a psychoneurologist Results: SPECT revealedsignificant decreasesin the cerebral blood flow compared with the before beginning of the IFN therapy in 3 (27.2%). Of these 3 patients, 1 complained of concentration, insomnia, and anxiety. Another exhibited insomnia, anorexia, anxiety, irritability, sense of guilt, and idea of suicide and was diagnosed to be in a depressive state by the psychoneurologist. The third patient showed no neuro-psychologic symptoms. None of the patients who did not show changes in SPECT images between before and after the IFN therapy developed neuropsychologic symptoms. Conclusions: IFN admini- stration was shown to deereasethe cerebral blood flow in some patients who showed the depressive symptoms. Since the depressive symptoms as adverse effects of IFN may relate a reduction in the cerebral blood flow.

P-298 EFFECT OF INTERFERON THERAPY ON BONE MINERAL DENSITY IN CHRONIC HEPATITIS C PATIENTS M.Shimoiani, S.Yasumura,H.Murata , T.Sato, T.Ishigami, T.Miyamoto, T.Kanda, and Y.Simizu Gast roenterology and Metabolism, Dept. of int. Medicine, Osaka Pre fec tura l General Hospital, Osaka, J a p a n

Interferon (IFN) used for t rea tment of chronic hepat i t is C inhibits the formation of osteoclasts. IFN therapy for chronic hepatitis C might lead to 1) the improvement of hepatic function and 2)changes in bone mineral density (BMD) due to the effect on suppression of bone absorption. In this study, we examined the relationship between the improvement of alanine transa minase (ALT) and BMD iongitudinally. Twenty-four patients with chronic hepati t is C were t rea ted with 6 ~ 9 M U / d a y of I F N - a 2 a for 24 weeks. We measured changes in BMD by dual X-ray absorp t iomet ry (DXA) and bone metabol ism paramete r s in subgroups of chronic hepat i t is C patients, classif ied as CR to PR (grop I ) o r NC to NR (group II ) by ALT response. There was no change in lumbar ver tebra l BMD in group I af ter IFN therapy, while total body BMD was s ignif icant ly h igher af ter IFN therapy than before IFN therapy. There was no change in lumbar ver tebra l BMD and total body BMD in group II af ter IFN therapy. Serum osteocalein was higher in group I than in group 1I, while other pa ramete r s showed no difference between the two groups, these findings indicated that IFN the rapy for chronic hepat i t is C pat ients increases cor t ical bone through improvement of hepatic function.

P-299 INFLUENCE ON GLUCOSE TOLERANCE FOR INTERFERON THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C K.Kaneko, T.Iijima, M.Nambu Dept. of Int. Medicine, Jun tendo Univ.of Medicine i l r ayasu Hospital, Chiba, J apan

To def ine the i n f l u e n c e on I n t e r f e r o n (IFN) c h a n g e s in diabetes mel l i tus wi th Chronic hepat i t i s C pat ients and glucose to l e rance in pa t i en t s wi thout diabetes mel l i tus was evaluated.

The study" inc luded 15 pa t ien ts of Chronic hepat i t i s C wi th n o n - i n s u l i n dependent diabetes mel l i tus (NIDDM) and 34 pat ients w i th c h r o n i c hepa t i t i s C wi thout diabetic pa t t e rn on 75g OGTT. Diabetes was agg rava t ed in 5 of the 15 (33.3%) pa t ien ts w i th NIDDM d u r i n g the period of IFN the rapy . 7 pa t ien ts in the diabetic g roup had been tested OGTT. Diabetes worsened in pa t ien ts who had had low i n s u l i n o g e n i c index and low basal i n s u l i n levels. In the pa t ients wi thout diabetes, the levels of fas t ing blood glucose (FBS), HbAlc, CPR, 1.5AG, i n s u l i n o g e n i c index, g lucagon, ACTH, hydrocor t i sone , g rowth ho rmone and ca t echo lamine were measured before and a f te r the IFN adminis t ra t ion . No s i g n i f i c a n t c h a n g e s were observed except for s ignif icant ly" inc reased FBS levels (P<0.05).

IFN t r ea tmen t of pa t ien ts w i th NIDDbl may f r e q u e n t l y (33.3%) a g g r a v a t e diabet ic control . Because pa t ien ts w i th low base l ine i n s u l i n levels and poor i n s u l i n r e a c t i v i t y in p a r t i c u l a r are at h i g h r isk, these pa t ients should be ca re fu l ly moni tored glucose level d u r i n g IFN the rapy . On the o the r hand, diabetes may develop very" r a r e l y in pa t ients wi thout the disease.

--"~'~" ASSOCIATION OF PLATELET GMPI40 AND THROMBOCYTOPENIA BY INTERFERON THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C A.Takahashi, M.Yamauchi, Y.Mizuhara, S.Shimada, F.Nishikawa, Y.Maezawa, G.Toda. let Dept. of Internal Medicine, The Jikei University School of of Medicine Tokyo, Japan

Thrombocytopenia is one of the serious side effect of interferon(IFN) therapy in patients with chronic hepatitis C; However, the mechanism of that effect has not been explicated. Human platelets contain more than ten members of adhesion molecules. To clarify the relationship between the platelet adhesion molecules and thrombocytopenia during IFN treatment, we measured GPIIa, GPIIIa and GMPI40 on platelets in ii patients with chronic active hepatitis during IFN therapy by a newly developed enzyme linked immunosorbent assay. Mean peripheral platelet count (xl0~/mm 3) decreased from 18.6 _+ 1.7 to 14.3 +_ 1.5 on the 14th day after IFN therapy. Platelet GPIIa decreased significantly from 411.1 _+ 312.0 (ng/mg. protein) to 134.1 _+ 181.1 (p<0.05). No significant change in the platelet GPIIIa after IFN therapy was found. Platelet GMPI40 increased significantly from 143.7 ± 52.4 (ng/mg. protein) to 276.4 _+ 114.4 (p<0.005). The significant correlatins between the reduction rate of peripheral platelet count and the induction rate of platelet GMPI40 was observed. These data suggest that platelet GMP 140 is excessively activated after IFN therapy. Thus, platelets may be trapped by the retieuloendothelial system, resulting in the thrombocytopenia.