HEPATOLOGY VoL 22, No. 4, P t . 2, 1995 A A S L D A B S T R A C T S 453A

1385 P , ~ / ~ E OF ~PI~I~IS C VIRUS DIF~fIOII HI IIOIDCI/)I~ G~II~tTHY (MG) t.lkncis. I.eascavilla. P.l~to*; LClew~to. G.san~aolo*. 14.vialiotti* g.~izzetto. ~ ~x~stroanterolo~y and *He~tology Division I l l s "Cana Sollie~o delia Sofferen:a' San Giovanni Rotomb (Fq) Ital~

Prelilinary data have shown an association bett~*en I ~ infection and KG in the co~se of V~ltiple Rieloan (M), galdenstrom's Ikcroqlohalis~ia (ml) and llon~Ional ¢.~m~athy of l~btomised Si~ificonce (l~OS). ~ae de~ee of liver involvanant in such pts is ~movn. On the other hand, the frequency of IIG am M L'W+ pts with chranLc liver diseases (Cl~) has not beu evaluated yet. kin of the stay is to reassus the relevance of ~'V infection in l~s. 57 pts with IIG in M, 111 and ~ c~rantiy followed up in the Outlkatisnts Clinic of the ~eMtology Division and witlmt an overt liver disease (group 1) ~era ISclu~L Male : female 2:1; ~ age: 63 Tts (range 45- 77). 350 HeY÷ pto with CLb (qroup 2)have also bee, studied. Nale:fenale 1:1; lean age 55 yrs; (range 38-~). ]iCY ~U by nested I ~ a~ o~wtypes by I]mLIPA were detemined. In ~ollp 1 ~ van detected in 8 pts (141), of thai 5 were qenotyped lb and the teanisisq 2a. In no cases cryoglokainaia or ~ antil~lie~ .ere f~md. 3outSptohed ki~hAL? a~lalive~biop~ysha~ed2canan of cirrhasis (I~) and 1 case of chronic active hepatitis (r~). In ~ 2, 11 pt8 had ~ ans~isted IIG (3,2t); 8 of fJlan eere virenic and q~otyped lb in 6 and 2a in the r ~ i M cases. ~-/oqlobulisemis ,as presant is 2; LI~ antibodies vere negative in al l . It histoloqy 5 pts bad L~ and 3 C~H. In conclusion along I~+ 1~ vith CUb I~ is an infrequent finding, eonparis9 the 2,8t prevalence of ~/infection in the ~ . r a l Italian population, HeV infection is 5 times higher in pts vith Ya ( ~ p I ) . This h i~ rate should ha related to the occurrence of a severe liver disease in such pts, vhi~ is c e r~ t i y ~ m c o r e d . In both qroups IIG ~lerl ises a severe histoleqical picture ant related to a difference in SeV genotypes.

1386 INTERRELATION BETWEEN HBV, HDV AND HCV INFECTIONS AND RESPONSE TO ALPHA INTERFERON THERAPY IN INTRAVENOUS DRUG ADDICTS WITH CHRONIC HEPATITIS P Marc~llin 1. C Cnstelnau 1. D. Lefave 2. A Kilani 1. M Martinotl,.J Descombes 1 . V Le Breton 1 . P D6nv 2. S Erlinuer I . 1 Service d'H6patologie et INSERM U24, H6pital Beaujon, Clichy ; 2Laboratoire de Bacl6riologie- Virologic, H6pital Avicenne, Bobigny, Universit6 Paris XlII, France.

Obieclivo : We studied anti-HlV positive and negative patients with chronic hepatitis and serological markers of HBV, HCV and HDV infections in order to assess (1) the relationship between HBV, HCV and HDV infections, and (2) the efficacy of alpha interferon therapy. Patients and methods : Sixteen intravenous drug abusers (9 anti-HIV positive), all men, aged 25 - 40 years and suffering from chronic active hepatitis were studied. All were positive for HBsAg, anti-delta IgM and anti- HCV. There was no difference between anti-HIV positive and negative patients with respect to duration of drug use (mean 7 years), duration of infection (mean 12 years) and histologic lesions (cirrhosis in 3 patients). All patients received recombinant interferon alpha 2b (Introna, Schering Plough),

. at the dose of 10 millions units, thrice a week for twelve months. Response was defined by the normalisation of serum ALT levels persisting after therapy. Results : Before treatment, HBV-DNA was not detected by conventional hybridization in any patient. HCV-RNA was detected by PCR in only one patient. HDV-RNA was detected by PCR in 14 patients. A sustained response was observed in 3 patients (19%), one of them being anti-HIV positive, (13, 18 and 21 months of posttreatment follow-up). All 3 respondera cleared HBsAg, anti-delta IgM and HDV-RNA. Marked histologio improvement was observed in the 3 responders. Treatment was interrupted in 5 patients because of decompensated cirrhosis (1), asthenia (3), decrease of CD4 lymphocyte count (1). Conclusion • In intravenous drug addicts with serological markers of HBV, HDV and HCV infections, HBV replication and HCV replication seem to be suppressed (even in anti-HIV positive patients). Alpha interferon therapy, ad ministered at the dose of 10 MU for 12 months, may induce a complete and sustained response with clearance of HBV and HDV infections.

1387 Identification of an endemic area for HCV infection in Liguria (Italv): HCV serotyping G.Marenco °, M.Rebora, A Roccatagliata, AM.Raffo, G.Varagona °, G.Imbereiadnri °, M.Coco ̂ , P.Bonanni*, GC. Icardi and P. Crovari °S.Corona Pietra Lig. Hosp.,*Dep. Public Health University of Florence, ^AVIS, Instit. Hygiene and Prev. Med. University of Genoa. Italy Introduction During 1993, a prevalence of anti-HCV higher than the mean usually found in our region was observed in voluntary blood donors living in Finale Ligure, near Genoa. In order to evaluate the real spread of HCV infection in that area, a seroepidemiological study was set up stratifying the residing population by sex and age. Materials and methods Five age classes were taken into account: 0-6, 7-14, 15-25, 26-45 and >46 years. A letter of personal invitation take part in the study was sent to 1607 individuals, corresponding to 15% of the resident population. The study protocol included the collection of anamnestic data and a blood drawing. All the collected samples were tested using commercially available screening and supplemental tests. In order to identify the HCV serotype, an enzyme- linked assay based on synthetic peptides of the NS4 region of the hepatitis C virus was used (Murex anti-HCV Serotyping assay). Results The compliance to the study was 43.3% of all the contacted subjects (697/1607). No ease of anti-HCV reactivity was detected in subjects under 25 years of age, while the prevalence of infected subjects was 3.7% and 12% in the classes 25-46 and >46 years respectively. The difference between these percentages is statistically significant (p<0.001). Samples resulting reactive for antibodies to the NS4 region of HCV in supplemental line-based tests (20/50) were serntyped. A definitive classification was not achieved for 7 sera (classification criteria not completely met). Out of the remaning 13 samples 10 were classified as seroptype 1 (78%) and 3 as serotype 3 (22%), Conclusion Our study suggest that a high circulation of HCV occurred in the Finale Ligure area in the past. Even if only a part of seropnsitive subjects were eligible for the serotyping test, the first results seem to confirm the prevailing transmission of a type 1 HCV in a closed epidemiological setting. Further confirmation of this hypothesis is awaited by the genotying of different HCV strains currently being performed.

1388 A NEW AND SIMPLIFIED TECHNIQUE FOR ORTHOTOPIC LIVER TRANSPLANTATION FROM GUINEA PIG TO RAT. W. Markl, 2. P. Hechenleimer 1,2. D. Candinas 2 p, Hengster 1 R. Linke 1. G. Klima 3 R. Mar~reiter 1 t Dept. of Transplant Surgery, University Hospital Innsbruck, Austria , 2 Sandoz Center for Immunnbiology, Harvard Medical School, Boston, MA, USA and 3 Dept. of Histology, University of Innsbrack

With the emergence of xenotransplantation and the option of using xenograft livers as bridging strategies in fulminant hepatic failure there is also a need for appropriate research tools to study discordant models of xenogeneic liver transplantation. The guinea pig to rat combination would represent a suitable small animal model but is associated with significant technical problems leading to primary non-function (PNF). We have therefore aimed at developing a simplified technique for orthotopic liver transplantation from guinea pig to rat and describe herein in detail the surgical technique. Methods: Male adult guinea pigs and unmodified, adult Lewis rats were used as donors and recipients, respectively. In group 1 (n=20) xenogeneic liver transplantation was performed u~ing a slighly modified technique as described originially by Kamada for orthotopic rat liver allotransplantation. In group 2 (n=5) the following two modifications were applied: i) The dissection of the infrahepatic vena cava (IHVC) as the pivotal point of the donor operation could be spared by using a syngeneic rat vena cava interposition graft fixed on a doublesided cuff made from a 14 G plastic catheter (Becton Dickinson). After perfusion of the donor liver this interposition graft was inserted into the IHVC. ii) After suprahepatic IVC anastomosis and portal vein anastomosis according to Kamada's technique the distal end of the cuffed interpostition graft was inserted into the recipient IHVC and tied with 6-0 silk. In order to gain flexibility in length and diameter of the interposition graft the middle part of the cuff was completely resected. Results: In group 1 dissection of the donor liver until cold perfusion required 60-90 minutes. Such long donor operations were poorly tolerated by guinea pigs and resulted in hypotension and subsequent graft failure in the recipient. In group 2 dissection of the donor liver until cold perfusion required 15-20 minutes and was well tolerated by the donor animal. Initial !obular reperfusion was complete in all grafts of group 2 whereas grafts in group 1 showed delayed and incomplete reperfusion. C o n e l u s i o n s : We suggest a modification of the donor operation for the guinea pig to rat xenograft liver model which significantly shortens the operation time and thereby improves graft perfusion.