Incidence and timing of infections in liver transplanted patients in Italy

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prevalence of MS after LT, yet it is unclear whether MS influences long-term outcome. Aim of our study was to assess the influence of MS on long-term post-LT survival. Patients and methods. Early (12 months after LT, n = 17) and late (>54 months after LT; mean 72 ± 16 months; n = 58) prevalence of MS, defined according to ATP III criteria, was evaluated in 75 patients (58/17: M/F; median age 51.1 years) transplanted at our centre between 1992 and 2002. Forty-three percent of patients were HCV positive. Maintenance immunosuppression was based on cyclosporine A in 42 (56%), and tacrolimus in 23 patients (30%). Family and personal pre-LT history of diabetes, hypertension, obesity and hyperlipidemia were recorded, as well as baseline anthropometric measures (weight, height, waist, hip) and clinical, biochemical and pharmacological data. All patients were re-evaluated five years after the initial survey. Results. Mean body mass index at enrolment was 26.9 ± 6.3 and did not increase through-out the study. Overall, thirty-two (42.7%) patients developed MS, with no difference between early (39%) or late (46%) development, both figures being higher (p = 0.001) than the reported prevalence of MS in an age-matched European non-transplanted general population (25.9%). Independent risk factors associated with the development of MS after LT were immunosuppression with cyclosporine A (p = 0.01), family history of cardiovascular disease (p = 0.05), age at transplant time (p = 0.02) and history of smoking (p = 0.009). Patient survival (Kaplan–Meier analysis) did not differ between patients with or without MS (10-year survival). Conclusions. MS is highly prevalent in liver transplanted patients and appear to be related to genetic/environmental factors and immunosuppression. However, MS does not influence survival after LT. doi:10.1016/j.dld.2007.12.086 ADEFOVIR RESISTANCE PATTERNS IN PATIENTS WITH LAMIVUDINE RESISTANT CHRONIC HEPATITIS B M. Fasano, M. Heichen, A. Guastadisegni, S. Palattella, G. Pastore, T. Santantonio Department of Internal Medicine, Immunology, and Infectious Diseases, Clinic of Infectious Diseases, University of Bari, Bari, Italy Background/aims. In lamivudine (LAM)-resistant chronic hepatitis B patients, a higher rate of adefovir (ADV)resistance than na¨ıve patients has been reported. Aims of this study were: (a) to evaluate ADV mutation patterns in LAM-resistant patients treated with ADV + LAM or ADVmonotherapy, (b) to ascertain if mutations selected during LAM therapy may predispose to ADV resistance, (c) to assess risk factors for ADV resistance development. Methods. Sixty LAM-resistant patients were treated with (or switched to) ADV-monotherapy (30 patients) or ADV+LAM combination therapy (30 patients), and followed for at least

12 months. The HBV reverse transcriptase region was amplified and directly sequenced before initiating ADV and at virological breakthrough. Results. Fourteen patients (23%) showed virological breakthrough (10/30 ADV-monotherapy and 4/30 LAM/ADV combination group). Known ADV-resistance mutations (rtA181V, rtN236T) were detected alone or in combination in 11/14 patients while only rtV214A/E, rtQ215H/P, and rt N238H were present in three patients. Overall, 11 different mutation patterns were identified. Before ADV treatment, apart from LAM-resistance signature mutations, several mutations were found including the rtA181T mutation already present in 2/14 ADV-resistance patients. Conclusions. In LAM-refractory patients, ADV-resistance is due to different patterns including known and novel mutations which can be selected during LAM therapy. ADVmonotherapy, especially in patients underdosed or with suboptimal virological responses after 48 weeks of therapy, favours ADV resistance. doi:10.1016/j.dld.2007.12.087 INCIDENCE AND TIMING OF INFECTIONS IN LIVER TRANSPLANTED PATIENTS IN ITALY P. Piselli a , M. Scuderi a , C. Zanfi b , A. Lauro b , S. Ferretti c , R. Santoro d , S. Barzoni Secchia a , M. Gabriel Arana a , C. Cimaglia a , G. Ferretti c , N. Gusman c , P.B. Berloco c , G.M. Ettorre d , G. Vennarecci d , A. Pinna b , P. Grossi e , A. Nanni Costa f , D. Serraino g , N. Petrosillo a , E. Girardi a , E. Puro a , G. Ippolito a a

INMI “L. Spallanzani” IRCCS, Roma, Italy “S. Orsola-Malpighi”, Bologna, Italy c Policlinico Universitario “Umberto I”, Roma, Italy d Polo Ospedaliero Interaziendale Trapianti (POIT), Azienda “S. Camillo” – INMI “L. Spallanzani”, Roma, Italy e Universit` a Insubria, Varese, Italy f Centro Nazionale Trapianti (CNT) ISS, Roma, Italy g SOC Epidemiologia & Biostatistica, Centro di Riferimento Oncologico (CRO) IRCCS, Aviano, Italy b Policlinico

Background and aim. Immune suppression after transplantation renders the transplant recipient more susceptible to a broad array of bacterial/viral or fungal infections. In this study, we assessed incidence rates and timing of infections in the first year after liver transplantation (LTX) among a group of Italian patients. Materials and methods. This analysis describes results of a prospective study on 126 consecutive LTX (75% males), who underwent transplantation in 3 centres in northern (Bologna) and central (Rome) Italy. The grafted organs were liver (in 124 patients) or liver + kidney (in 2 patients). Information was collected on pre-, intra- and post-operative risk factors (e.g., post-surgery transfusion, invasive procedures prophylactic procedures). All documented infections (either of bacterial, viral or fungal origin) were considered as infectious events, and were classified according to site of infection and causative

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agent; multiple events caused by the same agent occurred between 7 days were considered as a single event. Personyears (PYs) at risk, incidence rates (IR), IR ratios (IRR) and 95% confidence intervals (CI) were computed for viral, fungal and bacterial infections. Results. The 132 TX had a median age of 54.3 years and they were followed-up for 116.5 PYs (range 10–365 days after LTX). Fourteen deaths were recorded (12.0 deaths/100PYs); 260 infections were observed in 46 patients, with and overall IR of 223.2/100PYs (95% CI: 196.0-250.3). IR for bacterial, viral and fungal infections were 139.9, 66.1 and 17.2/100PYs, respectively. 47.3% of all infectious events occurred in the first 30 days of observation. Among considered risk factors in an univariate analysis, those significantly associated with an increate risk of infections (especially of bacterial or fungal origin) were: feminine sex, increate age, blood transfusion, ICU bound and a higher MELD score. Conclusions. These preliminary findings quantify the substantial burden of infections in the early post-transplant phase, urging for further studies aiming to better characterize risk factors associated with and increased risk and for the implementation of specific surveillance protocols for monitoring and reducing infectious compliances in transplanted patients.

P = ns) whereas the two-year intrahepatic distant recurrencefree survival was higher in group A (35% vs. 20%, P < 0.05) which also showed a longer interval to recurrence (median 18 vs. 12 months, P < 0.05). On intention-to-treat analysis, independent predictors of distant recurrence (p < 0.05) were persistence of viable tumour tissue after RFA application, tumour multiplicity and high levels of ALT, both at uni- and multivariate analysis. Conclusions. RF ablation is an effective method to treat small HCC, but patients treated for recurrent HCC have a shorter disease-free survival than patients submitted to first-line treatment.

doi:10.1016/j.dld.2007.12.088

Background. In patients treated with an anti HBV drug with a low genetic barrier to resistance (e.g. lamivudine) adding an appropriate non-cross-resistant second drug should be considered to prevent the emergence of resistance and viral breakthrough in those with suboptimal response (i.e. HBV–DNA < 3 log cp/ml after 24 weeks of treatment). However, virologic breakthrough and resistance have been observed in the long term even in patients with optimal response. Thus this strategy could be taken into consideration also in this setting but are no studies which assessed cost benefit of this strategy. Aims and methods. We designed a retrospective analysis of a prospective followed cohort of patients with HBV infection and without co-infections who started a new cycle of Nucleos(t)ide Analogues in a single center. From December 1st 2004 we offered Adefovir 10 mg/day add on to current therapy with Lamivudine 100 mg/day to all patients with HBV infection and with optimal response to lamivudine monotherapy (i.e. HBV–DNA < 2000 cp/ml by Versant 3.0 after no more than 24 weeks of treatment). All patients were followed thereafter with HBV–DNA measurement, liver tests and renal function assessment every 3 months. We defined “treatment failure” as a composite outcome including Virologic breakthrough (HBV–DNA > 20.000 cp/ml in >2 measurement) and/or renal damage (Creatinine >1.5 mg/dl with or without urinary changes). Results. Twenty patients accepted to add Adefovir and 39 refused Adefovir and continued Lamivudine monotherapy. Seventy five percent had cirrhosis 20% were immunosuppressed. There was no significant difference in clinical and virologic characteristics or in kinetics of response to lamivu-

PERCUTANEOUS RADIO-FREQUENCY ABLATION OF SMALL HCC: FACTORS RELATED TO CLINICAL OUTCOME AND RECURRENCE OF DISEASE F. Piscaglia, N. Celli, M.A. Zocco, M. Mancini, E. Sagrini, M. Mancini, A. Gianstefani, A. Bazzocchi, S. Costantini, R. Righini, L. Bolondi Division of Internal Medicine, Department of Internal Medicine and Gastro, University of Bologna, Italy Background. The role of previous treatments on diseasefree survival and recurrence rate in patients with small HCC treated with percutaneous radio-frequency ablation (RFA) has been incompletely assessed and was therefore investigated in the present study. Methods. A retrospective analysis identified 70 patients with small HCC (<3 cm, ≤3 nodules) who underwent RFA in our Unit between November 1999 and September 2006. RFA was applied as first-line treatment (group A, 35 patients) and for intrahepatic recurrent HCC after curative treatment (group B, 35 patients) Disease-free survival and time to local and distant recurrence was analyzed using Kaplan-Meier survival curves and compared using long-rank analysis. Patients and tumour-characteristics were evaluated for their prognostic significance by univariate- and multivariate-analysis. Results. Median follow-up was 16.5 months (range 6-72). The rate of single HCC was identical in the two groups (88.6%), but mean diameter was slightly smaller in group B (22 vs. 20 mm, P = 0.036). The two-year local recurrence free survival did not differ between groups A and B (65% vs. 55%,

doi:10.1016/j.dld.2007.12.089 “PROPHYLACTIC” ADEFOVIR “ADD ON” IS ASSOCIATED WITH A LOWER RATE OF VIROLOGIC BREAKTHROUGH IN PATIENTS WITH OPTIMAL RESPONSE TO LAMIVUDINE AND UNDETECTABLE HBV–DNA M. Puoti, F. Zacchi, S. Zaltron, A. Spinetti, S. Rossi, K. Prestini, M. Mendeni L. Biasi, G. Carosi Institute of Infectious and Tropical Diseases University of Brescia, Italy