- Email: [email protected]
1061 MOLECULAR PATHWAYS LEADING TO INSULIN RESISTANCE IN HEPATITIS C VIRUS INFECTION
POSTERS angiotensin system and its inhibitors may play a role in regulating the mechanisms of liver fibrosis development. Aim of the work: To investigate whether angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is related to progression of hepatic fibrosis and prediction of treatment response among patients with chronic hepatitis C. Patients and Methods: This study involved 90 patients suffering from chronic hepatitis C, 68 males and 22 females their ages ranged from 21 to 59 (mean: 42.6 years). All patients received antiviral therapy in the form of interferon. Patients were grouped according to the stage of liver fibrosis by biopsy into: goup1 (fibrosis: 0 or 1); group2 (fibrosis: 2 or 3) and group 3 (fibrosis from 4 to 6). One hundred seventy healthy subjects matched for age and sex with patients served as control group. ACE gene insertion/deletion (I/D) polymorphism was studied in all subjects. Results: Polymorphism D/D was significantly more prevalent among HCV patients compared to controls (65.6% vs 48.2%, p = 0.006). Degree of necroinflammation was significantly higher among patients with I/I polymorphism when compared to patients with D/D polymorphism (p = 0.04). No significant difference in the distribution of the D/D and I/I polymorphisms between the fibrosis groups and between responders and non-responders to interferon therapy. Conclusion: The D/D polymorphism of ACE may increase the susceptibility to chronic hepatitis C and the ACE genotype has no influence on hepatic fibrosis. 1060 ECONOMIC EVALUATION OF A MULTIDISCIPLINARY SUPPORT PROGRAM IN HEPATITIS C TREATMENT: PRELIMINARY RESULTS 1 M. Garc´ıa-Retortillo1 , V. Mart´ın-Escudero2 , M.D. Gimenez ´ , 1 1 1 3 3 I. Cirera , C. Marquez ´ , P. Castellv´ı , O. Urbina , E. Salas , C. Varela2 , R. Sola` 1 . 1 Liver Section, Hospital del Mar / IMIM / Universitat Aut` onoma de Barcelona, Barcelona, 2 Roche Pharma AG, Madrid, 3 Pharmacy Service, Hospital del Mar / IMIM, Barcelona, Spain E-mail: [email protected] Objectives: Adherence to the prescribed treatment regimen is an important factor that impacts on the success of therapy in chronic hepatitis C. The aim of this study was to develop a costeffectiveness analysis of a multidisciplinary support program (MSP) versus conventional treatment in a group of Hepatitis C (HC) patients. Methods: 278 naïve and mono-infected patients with HC were included in the study: 131 in Group 1 (MSP strategy) and 147 in Group 2 (conventional treatment approach). All patients were treated with Peg-IFN-alfa-2a and Ribavirin. The MSP not only included hepatologists and nurses, but also, pharmacists, psychologists and assistants; additionally uniform patient education, open and flexible visits scheduling, continued evaluation of psychiatric risk and active medication were carried out. A decision-tree model was built to estimate the incremental cost-effectiveness ratio (ICER) of MSP vs. conventional control. Unitary costs of HC drugs and professionals were included. Effectiveness was measured in terms of sustained virological response (SVR), adherence was defined as >80% dose administered. Results: For genotypes 1/4 (G-1/4), adherence was achieved in 92.4% of patients in Group 1 and 69.3% in Group 2 (p = 0.0005), for genotypes 2/3 (G-2/3) adherence was achieved in 96.9% and 93.2% in Groups 1 and 2 respectively (p > 0.05). SVR differed in the two groups: 66.7% in Group 1 and 48.9% in Group 2 for G-1/4 (p = 0.03) and 87.7% and 81.4% for G-2/3 (p > 0.05) for Groups 1 and 2 respectively. Cost per SVR was higher in Group 2 than in Group 1 (€24,079 and €20,197 in G-1/4; €8,351 and €7,723 in G-2/3). The ICER was €9,533/SVR in G-1/4 patients and Group 1 was dominant over Group 2 in G-2/3 patients. S410
Conclusion: The MSP could improve the adherence to the HC treatment and therefore the virological response, and could be also a cost-effective strategy compared with the conventional approach. 1061 MOLECULAR PATHWAYS LEADING TO INSULIN RESISTANCE IN HEPATITIS C VIRUS INFECTION L.C. Godoy1 , R.G. Fonseca2 , R.J. Carvalho-Filho1 , C.T. Emori1 , I.C. Melo1 , V.P. Lanzoni3 , C.P. Oliveira4 , J.T. Stefano4 , A.E.B. Silva1 , J.B. Pesquero2 , M.L.G. Ferraz1 . 1 Division of Gastroenterology, Hepatitis Section, Federal University of S˜ ao Paulo, 2 Department of Biophysics, 3 Department of Pathology, Federal University of S˜ ao Paulo, 4 Department of Gastroenterology, Faculty of Medicine of the University of S˜ ao Paulo, S˜ ao Paulo, Brazil E-mail: [email protected] Background and Aims: Previous studies have shown that chronic HCV infection can induce insulin resistance (IR), which reduces the efficacy of antiviral therapy and accelerates the progression of fibrosis. Molecular mechanisms involved in the pathogenesis of HCV-induced IR are not fully understood. Kinin B1 receptor (BDKRB1) is implicated in chronic inflammatory processes. This study aims to assess potential mechanisms of HCV interference with insulin signaling and expression of BDKRB1. Methods: Liver samples from HCV patients were obtained by percutaneous biopsy. Real-time PCR was performed to quantify the expression of the following genes: PPAR-gamma, IRS-1, IRS-2, SOCS-3, SREBF-1 and BDKRB1. 56 subjects were divided into three groups: HCV (n = 17); NAFLD (non-alcoholic fatty liver disease; n = 18) and Controls (without liver disease; n = 21). Quantification cycle (Cq) values of each gene from HCV group were compared with the values from the other two groups. Genes PMM1 and GAPDH were used as reference genes. IR was defined as a HOMA-IR > 2. Results: In HCV group, mean age was 41±11 years (65% women, 70% genotype 1). Advanced liver fibrosis (METAVIR F3/F4) and steatosis were observed in 5/17 (29%) and 8/17 cases (47%), respectively. IR was identified in 4/17 patients (24%). It was observed a decrease in the expression of IRS-2 in HCV patients (mean reduction of 57%) and NAFLD subjects (mean reduction of 74%), as compared to controls. It was also identified a lower expression of SOCS-3 and a higher expression of IRS-1 in HCV and NAFLD groups (P < 0.0001 and P = 0.009, respectively). HCV group showed significantly higher expression of SREBF-1, as compared to the NAFLD group (P < 0.05). All groups showed similar expressions of PPAR-gamma and BDKRB1 genes. Subgroup analysis revealed that HCV patients with IR, steatosis and F3/F4 had lower expressions of IRS-1 and IRS-2. A negative linear correlation was found between IRS-1 expression and HOMA score in HCV group (Spearman’s r = −0.69; P = 0.002). Conclusions: HCV chronic infection is associated with decreased intra-hepatic expression of IRS-1 and IRS-2, particularly in subjects with IR. However, neither SOCS-3 over-expression, as previously suggested in the literature, nor modifications in BDKRB1 expression seem to be implicated. 1062 NO EVIDENCE FOR AN IMPACT ON MORTALITY IN CHRONICALLY HCV INFECTED DRUG USERS B.P.X. Grady1 , A. Krol1 , C. van den Berg1 , J. van der Helm1 , J. Schinkel2 , R. Coutinho1,3 , M. Prins1 . 1 Infectious Diseases, Public Health Service Amsterdam, University of Amsterdam, 2 Department of Medical Microbiology, Academical Medical Center, Amsterdam, 3 Center for Infectious Disease Control, National Institute of Public Health and the Environment, Bilthoven, The Netherlands E-mail: [email protected] Background and Aims: The severe sequellae of chronic HCV (cHCV) have mainly been studied in hospital settings, often biased due
Journal of Hepatology 2010 vol. 52 | S319–S457
Conclusion: The MSP could improve the adherence to the HC treatment and therefore the virological response, and could be also a cost-effective strategy compared with the conventional approach. 1061 MOLECULAR PATHWAYS LEADING TO INSULIN RESISTANCE IN HEPATITIS C VIRUS INFECTION L.C. Godoy1 , R.G. Fonseca2 , R.J. Carvalho-Filho1 , C.T. Emori1 , I.C. Melo1 , V.P. Lanzoni3 , C.P. Oliveira4 , J.T. Stefano4 , A.E.B. Silva1 , J.B. Pesquero2 , M.L.G. Ferraz1 . 1 Division of Gastroenterology, Hepatitis Section, Federal University of S˜ ao Paulo, 2 Department of Biophysics, 3 Department of Pathology, Federal University of S˜ ao Paulo, 4 Department of Gastroenterology, Faculty of Medicine of the University of S˜ ao Paulo, S˜ ao Paulo, Brazil E-mail: [email protected] Background and Aims: Previous studies have shown that chronic HCV infection can induce insulin resistance (IR), which reduces the efficacy of antiviral therapy and accelerates the progression of fibrosis. Molecular mechanisms involved in the pathogenesis of HCV-induced IR are not fully understood. Kinin B1 receptor (BDKRB1) is implicated in chronic inflammatory processes. This study aims to assess potential mechanisms of HCV interference with insulin signaling and expression of BDKRB1. Methods: Liver samples from HCV patients were obtained by percutaneous biopsy. Real-time PCR was performed to quantify the expression of the following genes: PPAR-gamma, IRS-1, IRS-2, SOCS-3, SREBF-1 and BDKRB1. 56 subjects were divided into three groups: HCV (n = 17); NAFLD (non-alcoholic fatty liver disease; n = 18) and Controls (without liver disease; n = 21). Quantification cycle (Cq) values of each gene from HCV group were compared with the values from the other two groups. Genes PMM1 and GAPDH were used as reference genes. IR was defined as a HOMA-IR > 2. Results: In HCV group, mean age was 41±11 years (65% women, 70% genotype 1). Advanced liver fibrosis (METAVIR F3/F4) and steatosis were observed in 5/17 (29%) and 8/17 cases (47%), respectively. IR was identified in 4/17 patients (24%). It was observed a decrease in the expression of IRS-2 in HCV patients (mean reduction of 57%) and NAFLD subjects (mean reduction of 74%), as compared to controls. It was also identified a lower expression of SOCS-3 and a higher expression of IRS-1 in HCV and NAFLD groups (P < 0.0001 and P = 0.009, respectively). HCV group showed significantly higher expression of SREBF-1, as compared to the NAFLD group (P < 0.05). All groups showed similar expressions of PPAR-gamma and BDKRB1 genes. Subgroup analysis revealed that HCV patients with IR, steatosis and F3/F4 had lower expressions of IRS-1 and IRS-2. A negative linear correlation was found between IRS-1 expression and HOMA score in HCV group (Spearman’s r = −0.69; P = 0.002). Conclusions: HCV chronic infection is associated with decreased intra-hepatic expression of IRS-1 and IRS-2, particularly in subjects with IR. However, neither SOCS-3 over-expression, as previously suggested in the literature, nor modifications in BDKRB1 expression seem to be implicated. 1062 NO EVIDENCE FOR AN IMPACT ON MORTALITY IN CHRONICALLY HCV INFECTED DRUG USERS B.P.X. Grady1 , A. Krol1 , C. van den Berg1 , J. van der Helm1 , J. Schinkel2 , R. Coutinho1,3 , M. Prins1 . 1 Infectious Diseases, Public Health Service Amsterdam, University of Amsterdam, 2 Department of Medical Microbiology, Academical Medical Center, Amsterdam, 3 Center for Infectious Disease Control, National Institute of Public Health and the Environment, Bilthoven, The Netherlands E-mail: [email protected] Background and Aims: The severe sequellae of chronic HCV (cHCV) have mainly been studied in hospital settings, often biased due
Journal of Hepatology 2010 vol. 52 | S319–S457