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Adefovir resistance patterns in patients with lamivudine resistant chronic hepatitis B
A34
Abstracts / Digestive and Liver Disease 40 (2008) A1–A40
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
Abstracts / Digestive and Liver Disease 40 (2008) A1–A40
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