16 Donor arterial oxygen pressure is a major determinant of early post-operative adverse events in adult liver transplant recipients

16 Donor arterial oxygen pressure is a major determinant of early post-operative adverse events in adult liver transplant recipients

13 15 Open, multicenter, randomized, controlled trial to compare safety and efficacy of r-hIFN beta la alone or in combination with ribavirin in HCV ...

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15 Open, multicenter, randomized, controlled trial to compare safety and efficacy of r-hIFN beta la alone or in combination with ribavirin in HCV naive patients A. Craxi (1), G. Ideo (2), L. Demelia (3), A_ Picciotto (4), A_ Alberti (5), M. Pitaro (6) and M. Rizzetto (7) for the IBIS Study Group I) Institute of ClinicM Medicine, UniverMty of Palermo 2) Department of Internal Medicine and Gastroenterology. S Giuseppe Hospital, MiMn 3) Institute of Clinical Medicine, Univee~ty of Cagliari, 4) Department of Internal Medicine. University oJ Genoa 5) Department of Clinical and Experimental Medicine, University of Padova 6) Medical Department, gndusteia Fwnnaceutica Serono, Rome 7) UOADU Gasteolarepatolog& Moltuette Hospital, Turin

L I V E R T R A N S P L A N T A T I O N F O R W I L S O N ' S DISEASE (WD) V. Medici. S. Giarml, V. Mirante, M. Pompill, U. Cfllo, DF. D'Amico. A. Cavallari, GL Grazi, M. Salizzoni, R. Fassati, D. Forti. M. Castagneto, G. Tisone, U. Valente, R. Naccarato, E. Melada, G. Oasbarrini, GC. Stumiolo and S. Fagiuoli for Munotematica 2000 AISF OLT study Group Material and methods: A retrospective data collection analysis on liver transplants was carried out among Italian OLT centers. Results: WD was the indication in 37 cases out of 3026 adult transplant s (1.2%): 21 males (56.7%) and 16 females with a mean age of 27.5 yrs (range 15-56). The mean time elapsed between diagnosis and OLT was 40 months (range 0159). The main indication for OLT was ESLD in 71% (FHF 24.3%). Hepatic and neuro/psychiattic association was present in 29%. 55.6% of the patients underwent medical treatment; 53.6% were still on medical treatment at the time of OLT. Alcohol consumption was present in 16,1%; anti HCV positivity in 9.7% and HBsAg in 2.7%. At time of OLT, 3.8% of cirrhotic patients were in Child A, 34.6% in B and 61.5% in C.. Neurological symptoms significantly improved after OLT in 8/10 patients; no improvement was shown in any of the patients with psychiatric symptoms (8). 10 patients (27%) died after OLT, at a mean time of 41.2 months. Patients and grafts survivals at 6, 12, 36, 60, 84, 120 months were 89.2, 89.2, 82.9, 75.6, 70.5 and 58.8% and 85.3, 85.3, 82.7, 70, 70 and 45.8%, respectively. Retransplantatien was required in 4 cases (10.8%), as a result of vascular disease (2), primary liver non function (1), de aovo HCV hepatitis(l). Survival of patients with mixed hepatic and neuropsychiatric involvement was significantly reduced compared with patients with isolated hepatic disease (p=0,04). The mean cause of death was sepsis, which oecured in 5 out of 8 cases (mean time o f death 43,6 months). In one case death occured as a result of severe and progressive deterioration of neuro/psychiatric status within the first postOLT month. Conclusions: 1) About half of pts was not on medical therapy at the time of OLT. This could represent an underestimation of the necessity of treatment for this peculiar disease 2)WD characterized by isolated hepatic involvement is a rare but excellent indication tbr OLT 3)WD patients with associated neuropsychiatric manifestation of the disease show a significantly reduced survival ¢)OLT appears to exert a positive impact on neurological but not on psychiatric symptoms in patients with WD with mixed hepatic and neuro/psychiatric involvement.

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16 INFECTION BY PRE-S2 HBV VARIANTS IS HIGHLY PREVALENT IN PATIENTS WITH LIVER DISEASE AND SIGNIFICANTLY ASSOCIATES WITH HEPATOCELLULAR CARCINOMA. IDENTIFICATION OF THE pre-S2 VARIANTS BY NON-SEQUENCING MOLECULAR APPROACHES. L.Costantino, S.Brancatelli, G.Caccamo, I.Cacciola, G.Squadrito. T.Pollicino. G.Raimondo. Dipartimento di Medicina lnterna. Poli¢linico Universitario di Messina.

Background/Aims - Several reports described the occurrence of infection by proS2 defective HBV variants in association with severe forms of acute and chronic hepatitis. The defectiveness of these variants is related to the presence of mutation(s) at the ATG start eodon and (or) in-frame deletion into the proS2region of the HBV genome. Until now, proS2 variants could be detected only through sequencing analysis of the entire genomic region, and this represented the main difficuti~ for investigating their prevalence in the general population of HBV carriers and for exploring the hypothesis of their close association with severe liver diseases. This study evaluated the prevalence of preS2-defective variants in a large series of chronic HBV infected patients through the use of non-sequenclng molecular approaches. Patients and Methods - We examined HBV isolates from 110 HBV chronic carriers: 15 were healthy carriers (HC/: 50 had chronic hepatitis (CH); 25 were cirrhotics : 19 had hepatocellular carcinoma (HCC). The entire proS2 genomic region was amplified by PCR technique. The products of amplification were processed: (A) by electrophoresis on a 3% acrylamide gels that were subsequently silver stained to reveal deleted genomes; (B) through digestion by Nlalll restriction enzyme that cuts at the restriction site 5'CATG-3' and thus it is able to digest the wild ATG start codon The products of digestion were run on a 2% agarose gel and were revealed by ethidium bromide staining. Lack of digested bands identifies the HBV genomes carrying mutated proS start codon. The results were confirmed by cloning and sequencing analyses. Results - See table below Diagnosis n°pts d ted ATG mutated wild+deleted wild+ATGmutated ~ariantcases HC ° 15 0 0 _ CH o *

50

4

5

3

25

Cirrhosis ° * 26

2

I

I

13

HCC ° *

3

0

4

° p > 0.0001

19 * p = 0.02

Conclusions - /I) Our non-sequencing molecular methods simplify the identification of all forms ofpreS2 HBV variants, and appear to be sensitive and specific. (2) ProS2 defective HBV variants are highfy prevalent in patients with active viral int~ction and liver disease. (3) Infection by these variants significantly associates with HCC.

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PEGylated IFN alfa in association with ribavirin is currently the gold standard in the treatment o f chronic hepatitis C. However, a significant percentage o f patients (between 13% and 19%) must stop treatment due to the occurrence o f adverse events. Preliminary results in small trials suggest that IFN beta can be an effective treatment for chronic hepatitis C with a good safety profile. One hundred and two patients (out o f 108 screened) with chronic hepatitis C never treated with IPNs were randomized in an open trial performed in 6 centers in Italy to receive 6 M I U o f r-hl]TN beta l a sc every day for 24 weeks alone (Group 1, n=51) or in combination with ribavirin (Group 2, n=51) at the dose o f 1,000 mg daily in patients <70 Kg and 1,200 rag in patients >70 Kg. Baseline characteristics (age, sex, viral load) were similar in the two groups and 60.78% of patients in Group 1 and 64.70% o f patients in Group 2 were infected by genotype 1. The virologic response rate al%er 24 weeks o f treamaent was 29.4% in Group 1 and 41.2% in Group 2. The sustained virologic response rate al%er 24 weeks o f follow-up without treatment was 21.56% in Group 1 and 27.45% in Group 2. Overall, both treatments were very well tolerated. The hematological and hematochernical parameters were unmodified at the eed of treatment compared to baseline, with the exception o f a significant decrease of Hb levels in patients who received combined treatment. AB patients in Group 1 completed the treatment up to 24 weeks, whereas 3 patients in Group 2 stopped therapy due to adverse events, two o f which related to study drug. In conclusion, r-hIFN beta l a alone or in combination with ribavirin appears to be a safe and effective treatment in chronic hepatitis C naive patients and represents an alternative for patients who do not tolerate PEGylated WN alfa and ribavirin.

D O N O R ARTERIAL O X Y G E N PRESSURE IS A MAJOR D E T E R M I N A N T OF E A R L Y POST-OPERATIVE ADVERSE E V E N T S IN A D U L T LIVER TRANSPLANT RECIPIENTS Ginanni Corradini S, Elisei W, De Marco R~ Siciliano MT, *Pretagostini R, *Iappelh M, *Pugliese F, "Ruberto F, *Stabile D, *Casciaro G, Merli M, Attili AF, *Berloco P, "Rossi M. Div Gastro Dip Med Clinica and *Dip Chir Generale "Paride Stefanini", Universita' "La Sapiertza" Roma. Background & Aims: Adverse events occurring shortly after liver transplantation (AE) increase hospital stay and costs and negatively influence lung-term prognosis. It is not known whether arterial oxygen pressure (PaOs) o f cadaveric donors influences the outcome o f liver transplantation. We investigated the association o f different variables, including donor PaO2, with the short-term outcome of liver transplantation. Methods: Forty-six primary cadaveric orthotopic nonstatus I whole liver adult transplantations were studied during the period 02/2001-9/2002 at a singe institution. The following variables were recorded at transplantation: recipient age and M E L D score, donor age, blood sodium, days of ICU and pre-harvesting PaO2 and cold ischemia time. Patients were prospectively studied for bile flow, blood chemistry and the occurrence of AE. Results: In 18 patients the following AE occurred during the first postoperative week: primary non-function (5), primary poor function (6), hepatic artery thrombosis (2), acute rejection (1) and altered mental status (4). Twenty-eight patients were flee o f AE at least two months after transplantation. After transplantation, the group with AE as compared with the group flee o f AE was characterized by: a) a lower mean cumulative post-operative three-day bile flow (222.7±56.7 vs 421.9i-43.0 ML; p<0.01); b) a higher blood total bilimbin concentration at day 1 (5.9±0.7 vs 4.1±0.5 mg/di; p