4 4 2 A A A S L D A B S T R A C T S HEPATOLOGY O c t o b e r 1995

1341 INFLUENCE OF SERUM ZINC LEVEL TO RESPONSE O F INTERFERON IN PATIENTS WITH CHRONIC HEPATITIS C. M Kuboki T H Shinzawa, Y Terui, K Suzuki, E Yoshii v T Takahashi. The Second Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan.

It is well known that the serum zinc level is decreased with advanced hepatit is. The aim o f this s tudy was to clarify the influence o f the serum zinc level to the response o f interferon (IFN) a treatment. M e t h o d s We examined pretreatment serum samples from 35 patients with chronic hepatitis C who were subsequently t reated with natural IFN a 110 MU daily for 2 wks and 10 MU t.i.w, for 22 wks). Serum zinc level was measured by atomic absorpt ion analysis (normal range : 6 5 - 1 1 0 / ~ g / ~ ) . Complete responders (CR) were defined as those who showed disappearance of serum HCV RNA by RT-nested PCR at the end o f treatment and 6 mo af ter the treatment. Transient responders (TR) showed serum HCV RNA disappeared during t reatment and became posit ive af ter the completion. No responders (NR) were continuously detected serum HCV RNA. Resu l t s Mean serum zmc level was 76.4_+10.8(/~ 9 / ~ ) in CR (n=12) groups, 66.0_+ 9.8 in TR (n=12) groups and 66.4_+10.0 in NR (n=11) groups. From the aspect o fb iochemical response, mean serum zinc level was signif icant higher in sustained response group(72.4+ 10.4, n=26) than transient or no responder groups (61.8+11.5, n=9). Conc lus i ons The serum zinc level affected biochemical response to IFN. These data suggest that efforts to zinc supplementation may lead to enhance IFN efficacy.

1342 i s INTERFERON ALPHA ATHEROGENIC ? ; P. K u d ~ r , A. Abergel, P. Jouanel*, C. Bonny, H. Bran, C Henquell °, H. Lafeuille °, G.Bommelaer.

Service d 'H~pa togas t roen t6ro log ie et * Laboratoire de Biochimie, H6tel Dieu ; o Laboratoire d e Virologic, Facult6 de M6decine, Clermont Ferrand.

I n t e r f e r o n - a ( I F N ) is the t r ea tmen t of choice f o r Chronic Hepatitis C (CHC). Two recent reports have s u g g e s t e d that serum t r ig lycer ides (TG) and cholesterol (XOL) increased during IFN therapy (Hepatology 1992;A68 ; Gas t roentero logy 1993;A918). Moreover, the second a u t h o r found a decrease of the cardiac risk index (XOL/XOL HDL). AIM : This study was perfomed to determine the effect o f IFN on serum TG, XOL, Apo AI and Apo B in adults undergoing treatment for HCV. METHODS : 15 patients were evaluated (mean age 48 + 2.8 years ; 46% were male). All had (+) anti-HCV by t h i r d genera t ion antibody assay and RIBA-4, ( - ) s e ro log i e s for a l l o the r causes of chronic hepatitis, and liver h i s t o l o g y compatible with CHC. All patients were treated with 3-6 MU of IFN TIW for six months. Serum XOL, TG, Apo A1 and Apo B were monitored before and during treatment (3 to 6 m o n t h s ) . R E S U L T S : M e a n serum Apo AI decreased from 1,33 +0 .06 ( m + S.E.M) to 1.08 + 0.04 g/1 (p<0,001). No statistical d i f f e r e n c e was found for serum Apo B and XOL. Mean serum 1G increased from 1,31 +_0.21 to 2.8i + 1.06 mmol/l (p =NS). Apo B/Apo A1 cardiac risk index increased from 0.80 + 0.09 to 0.97 + 0.1l (p<0,05). CONCLUSION : 1) In contrast with the other reports we have 'nt found a s igni f icant elevation of serum TG ; 2) In te r feron induce a s ignif icant elevation in the Apo B / A p o A1 cardiac risk inde x ma in ly by serum Apo A1 decrease ; 3 ) Further studies are needed to know if the cardiac risk i n d e x increase induced by IFN has a clinical significance.

1343 COMBINATION THERAPY ACHIEVES BIOCHEMICAL BUT NOT VIROLOGICAL OR HISTOLOGICAL RESPONSE IN INTERFERON- RESISTANT HEPATITIS C. M. Kuqelmas, B. Yen-Lieberman, RJ Tuthill, WD Carev. Cleveland Clinic Foundation. Cleveland, OH

There is no consensus on management of interferon-resistant hepatitis C (IFN-R). Preliminary data suggests de-irenization (DI)and ursodiol (UDCA) may improve the response rate to IFN. Aim: To assess the effect ofcombiningDl+lFN+UDCAinpatientswith IFN-R. Methods: Patients with IFN-R underwent DI by weekly phlebotomy (400-500 mL). DI was achieved when 2 of 3 criteria were met: Hgb <12 mg/dL, transferrin saturation <11%, ferfitin <15 ng/mL. Patients then received IFN 3 MU tiw and UDCA 10-15 mg/kg/day for 24 weeks. ALT levels, HCV-RNA levels, liver histology and hepatic iron concentrations were followed. Comparisons were made using t-tests and Fisher's exact test. Results: Fourteen patients (mean age 39, 8 M) were enrolled. Ten completed the study, 1 is still in follow-up, 1dropped out at 3 months of IFN + UDCA, ahd 2 did not complete phlebotomies. A mean of 8.5 phlebotomies (range 3-20) were needed to achieve DI. Serum ALT levels fell significantly and became normal in 2 patients. Phlebotomy did not reduce viral load. Subsequent treatment with IFN & UDCA produced normalization of ALT in 4 others. None achieved viral clearance. There was n~ significant change seen in i I paired liver biopsies: After 6 mos. of FlU 2/10 patients had sustained ALT response.

ALT (U/L) Normal ALT HCV-RNA ImEqxl 0 ~) KNODELL score

Entry (n=l 2) 121 +20* 0% 100~32 5.G9~.86

AfterDl(n=l 2) 62~9"* 17% 87±27

After 64±13** 50%'*" 118±54 6.55±.73 IFN+UDCA(n= 12)

6 mo F/U (11=10) 84±16 20%

*All values are expressed as mean+SEM **p<.03 ***p<.01 Conclusions: In patients who fail to respond to a standard course of IFN, 1) combination therapy achieved a 500 short term and 20% long term biochemical response, 2) no virological or histological improvement was seen. 3) This effect seems to be mediated through a mechanism other than viral clearance. Long term follow-up is needed to define the significance, if any, of ALT improvement in the outcome of this chronic infection.

1344 PROTECTIVE EFFECT OF LIDOCAINE AGAINST WARM ISCHEMIA IN THE MODEL OF LIVER TRANSPLANTATION FROM THE NON-HEART BEATING DONOR. T Kusano. M Shiraisi. J Hara. T Mivaouni. S Hirovasu. T Aihara. Y Muto. The First Department of Surgery, University of Ryukyu, Okinawa. [P urpose]Lidocaine is known to reduce the size of infarction in the model of cardiac ischemia/reperfusion model. We have tested this potential role of lidocaino in the model of liver transplantation from the non-heart heating donor in rat. [Materials and Method] 1 ) Male wister rats weighing 250 to 3O0g were subjected to splenic transposition for more than 3 weeks to acquire port-systemic shunt. The hepatic artery and portal vein were clamped for I hour. Hepatic blood flow (laser doppler flowmetry), serum AST, ALT levels and liver histology were examined after reperfusion. Experimental groups were designed as follows, group1 (physiological saline 1 ml/ l 0min), group2 (lidocaine lOmg/kg/ml/10min before damping) or group3 (group2 + administration of the lidocaine on reperfusion). 2 ) OLTx model; In the donor, the descending aorta was damped to create no-flow warm ischemia of the liver. Lever was perfused via the aorta, with UW solution containing lidocaine after 10, 20, 30 minutes of ischemia. Then the liver was harvested and transplanted into the syngenelc recipient. [Results] 1 ) In group 2 and 3, the tissue blood flow ranged from 10 to 20 ml/min/100g which was significantly greater than group 1 (p<O.05). Supplemental lidocaine administration on reperfusion was also effective in suppressing the increase of AST, ALT levels in group3. Z ) In the OLTx model, 10, 20 and 30 minutes of warm ischemia resulted in the survival rate (>30days) of 3/5, 0/5, O/S respectively in control group, and 5/5, 4/5, 2/5 respectively in lidocaino group. [Conclusion] 1, I idocaine was effective to mitigate the ischemia/ reperfusion injury in no-flow warm ischemia model. 2. Udocaine improved the survival rate of the recipients in the model of liver transplantation from the non-heart heating donor.