M.L. Abate

Adipose tissue insulin resistance is associated with macrophage activation in non-diabetic patients with non-alcoholic fatty liver disease

M. Marietti 1, C. Rosso1, M. Gaggini2, C. Saponaro2, K. Kazankov3, E. Buzzigoli 2, H.J. Moller4, G.P. Caviglia1, M.L. Abate1, A. Smedile1, G.M. Saracco5,6, H. Vilstrup3, J. George5,6, H. Gronbaek3, A. Gastaldelli 3, E. Bugianesi1 1 Department of Medical Sciences, University of Torino, Torino, Italy 2 Cardiometabolic Risk Unit, Institute of Clinical Physiology, CNR, Pisa, Italy 3 Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark 4 Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark 5 The Storr Liver Centre, University of Sydney and Westmead Hospital, Westmead, Australia 6 Department of Oncology, University of Turin, Turin, Italy

P840 ALTERATION IN LIPID METABOLISM AFTER AN ORAL FAT LOAD IN PATIENTS WITH NAFLD

P840 ALTERATION IN LIPID METABOLISM AFTER AN ORAL FAT LOAD IN PATIENTS WITH NAFLD L. Mezzabotta, E. Vanni, C. Rosso, M. Gaggini, R. Gambino, E. Buzzigoli, C. Saponaro, D. Ciociaro, M.L. Abate, F. Saba, F. Salomone, G.P. Caviglia, S. Carenzi, A. Smedile, M. Rizzetto, M. Cassader, A. Gastaldelli, E. Bugianesi. Medical Sciences, University of Turin, Turin, Cardiometabolic Risk Unit, Institute of Clinical Physiology – CNR, Pisa, U.O.C. of Gastroenterology, Azienda Sanitaria Provinciale di Catania, Catania, Italy E-mail: laviniaemme@hotmail.com

P843 ALTERATION IN GLUCOSE METABOLISM AFTER AN ORAL GLUCOSE LOAD AND RELATIONSHIP WITH LIVER DAMAGE IN PATIENTS WITH NAFLD

P840 ALTERATION IN LIPID METABOLISM AFTER AN ORAL FAT LOAD IN PATIENTS WITH NAFLD L. Mezzabotta, E. Vanni, C. Rosso, M. Gaggini, R. Gambino, E. Buzzigoli, C. Saponaro, D. Ciociaro, M.L. Abate, F. Saba, F. Salomone, G.P. Caviglia, S. Carenzi, A. Smedile, M. Rizzetto, M. Cassader, A. Gastaldelli, E. Bugianesi. Medical Sciences, University of Turin, Turin, Cardiometabolic Risk Unit, Institute of Clinical Physiology – CNR, Pisa, U.O.C. of Gastroenterology, Azienda Sanitaria Provinciale di Catania, Catania, Italy E-mail: laviniaemme@hotmail.com

346 INCREASED LIVER EXPRESSION OF INFLAMMATORY MEDIATORS IS ASSOCIATED WITH HEPATIC INSULIN RESISTANCE IN LEAN, NON-DIABETIC PATIENTS WITH CHRONIC HEPATITIS C

E. Vanni1, M.L. Abate1, E. Gentilcore1, C. Elia1, R. Gambino2, M. Cassader2, A. Smedile1, M. Rizzetto1, G. Marchesini3, A. Gastaldelli4, E. Bugianesi1. 1Division of Gastro-Hepatology, 2Department of Internal Medicine, San Giovanni Battista Hospital, University of Turin, Turin, 3Clinical Dietetics, University of Bologna, Bologna, 4Metabolism Unit, C.N.R. Institute of Clinical Physiology, Pisa, Italy E-mail: estervanni@yahoo.it

Identification of HBV-DNA markers that are predictive of response to lamivudine therapy in patients infected with HBV precore variants

Lamivudine is initially highly effective in patients with hepatitis B e antigen-negative (HBeAg) chronic hepatitis B, but its long-term efficacy is burdened by high rates of virologic relapse. We analyzed the DNA sequence of HBV polymerase (domains A to E), and the HBV precore/core regions in 26 HBeAg-negative patients (genotype D, 16 with G1896A, 16 with A1762T/G1764A, 11 with both) treated for 21-48 months with lamivudine to determine if there was a relationship between specific HBV-DNA sequence patterns and long-term treatment response. After a minimum of 21 months of therapy, seven patients (27%) were responders (normal ALT, HBV-DNA-), 12 (46%) breakthroughs (following initial virologic response), and 7 (27%) non-responders (sustained elevated ALT, HBV-DNA+). Two HBV-DNA polymerase polymorphisms, present in the pretreatment serum samples, were correlated with extended treatment failures (breakthrough or non-response). Leucine was present at rt9 1 in 17 of 19 patients with long-term treatment failure, and a cysteine was present at rt2.56 in 13 of these 19 patients. All 7 long-term responders had an isoleucine at rt91 and a serine at rt2.56. Under therapy, reversion of A1762TIG1764A was observed in 4 of 13 patients (31%), and of G1896A in 3 of 12 (25%). YMDD Mutations (confirmed by INNOLiPAa) analysis) were found in 7/12 of the relapsing patients at the time of breakthrough. Our data suggest that specific HBV-DNA sequences present before treatment may predict long-term response to lamivudine, permitting therapy to be targeted to those individuals who are most likely to have sustained clinical benefit.