- Email: [email protected]
P773 ANGIOGENIC BIOMARKERS OF CHRONIC HEPATITIS C PROGRESSION TO HEPATOCELLULAR CARCINOMA
POSTERS Results: Frequency of CD14+ monocytes was higher in CHC patients than those in the controls (P < 0.05). There was a positive correlation between CD14+ monocyte frequency and severity of liver fibrosis (r = 0.617, P < 0.05). Expressing IL-6, IL-8 and TNF-a monocytes were increased and expressing IL-10 monocytes were decreased, but no correlation with hepatic fibrosis was observed in the patients. Hepatic CD163 expression was correlated with hepatic fibrosis (r = 0.826, P < 0.05). Compared to the controls, serum sCD163 levels were significantly higher and gradually increased with progression of hepatic fibrosis in CHC patients (P < 0.05). Conclusions: CD14+ monocytes and CD163+ macrophages play a critical role in hepatic fibrogenesis in chronic HCV infection. Detection of the frequency of peripheral CD14+ monocytes and hepatic CD163+ macrophages might provide a new evidence for predicting progression of hepatic fibrosis in CHC. P773 ANGIOGENIC BIOMARKERS OF CHRONIC HEPATITIS C PROGRESSION TO HEPATOCELLULAR CARCINOMA R. Lopez-Rodriguez1 , A. Hernandez-Bartolome´ 1 , M.J. Borque2 , 3 Y. Rodriguez-Munoz ˜ 1 , J.R. Vidal-Castineira ˜ , L. Rodrigo4 , 5 6 J.M. Ladero , F. Abad-Santos , P. Munoz ˜ de Rueda7 , J. Salmeron7 , Y. Real1 , L. Gonzalez-Moreno1 , J. Garcia-Samaniego8 , A. Mart´ınAlg´ıbez9 , L. Garcia-Buey1 , R. Moreno-Otero1 , P. Sanz-Cameno10 . 1 Liver Unit, Hospital Universitario de la Princesa, Universidad Aut´ onoma de Madrid, Instituto Investigaci´ on Sanitaria Princesa & CIBERehd (ISCIII), 2 Molecular Biology Unit, Hospital Universitario de la Princesa, Universidad Aut´ onoma de Madrid, Instituto Investigaci´ on Sanitaria Princesa & CIBERehd (ISCIII), Madrid, 3 Immunology Service, Hospital Universitario Central de Asturias, 4 Gastroenterology Service, Hospital Universitario Central de Asturias, Oviedo, 5 Gastroenterology Service, Hospital Cl´ınico San Carlos, IIS Hospital Cl´ınico San Carlos, 6 Clinical Pharmacology Service, Hospital Universitario de la Princesa, Universidad Aut´ onoma de Madrid, Instituto Investigaci´ on Sanitaria Princesa & CIBERehd (ISCIII), Madrid, 7 Gastroenterology Service, Hospital Universitario de San Cecilio & CIBERehd, Instituto de Salud Carlos III, Granada, 8 Liver Unit, Hospital Carlos III & CIBERehd, ISCIII, 9 Gastroenterology Service, Hospital Universitario Doce de Octubre, 10 Liver Unit, Hospital Universitario de La Princesa, Instituto de Investigaci´ on Sanitario Princesa, CIBERehd (ISCIII) & Fundaci´ on Cient´ıfica AECC, Madrid, Spain E-mail: [email protected] Background and Aims: Chronic hepatitis C (CHC) is one of the leading causes of liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC progression is highly heterogeneous as a result of environmental, viral and genetic factors. Genetic variants of major inflammation, fibrosis and angiogenesis mediators may be decisive for the prognosis of CHC patients. Our aim is to study the influence of single nucleotide polymorphisms (SNPs) of angiogenic genes on CHC progression and plasmatic levels of angiogenic-related factors. Methods: 384 SNPs selected by their potential effects on gene expression or functionality from 44 candidate genes (angiogenic factors and receptors) were genotyped in 381 patients: 268 with CHC (F0–1=50, F2=80, F3=32, F4=106) and 113 with HCC of CHCetiology. Association between SNPs and CHC progression (F0–1 vs. F2–4, F0–1 vs. HCC and F2–4 vs. HCC) were analyzed by PLINK software. Plasmatic levels of significant related factors were measured in those patients whose plasma was available: 53 with CHC (F0–1=17 and F2–4=36) and 31 with HCC. Results: 13 SNPs located in 8 angiogenic genes were significantly associated with CHC progression (p < 0.01). Of those, 4 SNPs were related to significant fibrosis (F0–1 vs. F2–4), 4 to HCC progression (F2–4 vs. HCC) and 7 to the evolution from F0–1 to HCC. Interestingly, plasmatic levels of main associated angiogenic factors (HGF, Ang2 and Tie2) were significantly related to HCC progression. S328
Conclusions: The characterized genetic variants associated with CHC progression and the plasmatic levels of related-angiogenic factors could be a valuable tool for HCC prevention and clinical management of these patients. P774 CLINICAL IMPACT OF AN INTERNET-BASED TOOL TO HELP GUIDE TIMING OF HCV THERAPY J. Schulz1 , I.M. Jacobson2,3 , P.Y. Kwo4 , A.J. Muir5,6 , N. Terrault7 , E. King1 , M.S. Sulkowski8 . 1 Clinical Care Options, LLC, Reston, VA, 2 Weill Cornell Medical College, 3 NewYork-Presbyterian Hospital, New York, NY, 4 Indiana University School of Medicine, Indianapolis, IN, 5 Duke Clinical Research Institute, 6 Duke University School of Medicine, Durham, NC, 7 University of California, San Francisco, CA, 8 Johns Hopkins University School of Medicine, Baltimore, MD, United States E-mail: [email protected] Background and Aims: Practice guidelines provide insufficient guidance on timing of HCV therapy, particularly with the rapid evolution of treatment options. We evaluated whether expert recommendations on timing of HCV therapy, delivered via an online decision support tool, would affect management decisions of community practitioners. Methods: 5 HCV experts made recommendations for 900+ patient scenarios. Tool users enter patient liver disease stage, HCV genotype (GT), treatment history, and interferon (IFN) tolerability. Before expert recommendations are revealed, users enter their intended management approach. The tool then displays expert recommendations for the specific patient scenario. Finally, users indicate if the recommendations change or confirm their approach. Results: The tool was posted online in October 2013. 427 cases were entered within 21 days; 41% were real (not hypothetical) patients; 70% were GT 1; 40% had F3/F4 fibrosis, 57% were treatment naive. 18% of users indicated expert recommendations changed their intended management approach. Experts would defer therapy (PR ± BOC or TVR) in all 900+ patient scenarios in favour of future options. By contrast, clinicians planned to start therapy in 45% of cases entered; 33% of those would change plans based on expert recommendations. All experts plan to treat all GT 2 patients once sofosbuvir is available. Recommendations varied most for GT 3 HCV and according to liver disease severity. Additional comparisons of expert and user responses will be presented. Conclusions: Preliminary data indicate an online tool providing customized, patient-specific expert advice may increase the number of clinicians who make optimal decisions regarding timing of treatment for HCV. P775 HEPATITIS C VIRUS INFECTION AND THE ASSOCIATED RISK FOR DIABETES MELLITUS G.T.-W. Shaw1 , M.-H. Lee1,2 , H.-I. Yang1,3 , C.-L. Jen1 , S.-N. Lu4 , L.-Y. Wang5 , S.-L. You1 , G. L’Italien6,7 , Y. Yuan6 , C.-J. Chen1,8 , for the REVEAL-HCV Study Group. 1 Genomics Research Center, Academia Sinica, 2 Institute of Clinical Medicine, National Yang-Ming University, Taipei, 3 Molecular and Genomic Epidemiology Center, China Medical University Hospital, Taichung, 4 Department of Gastroenterology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, 5 MacKay Medical College, Taipei, Taiwan; 6 Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, 7 School of Medicine, Yale University, New Haven, CT, United States; 8 Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan E-mail: [email protected] Background and Aims: The associations between hepatitis C virus (HCV) infection and diabetes mellitus remained inconclusive. The community-based long-term follow-up study aimed to evaluate the relationship between HCV infection and diabetes mellitus by considering conventional risk factors.
Journal of Hepatology 2014 vol. 60 | S215–S359
Conclusions: The characterized genetic variants associated with CHC progression and the plasmatic levels of related-angiogenic factors could be a valuable tool for HCC prevention and clinical management of these patients. P774 CLINICAL IMPACT OF AN INTERNET-BASED TOOL TO HELP GUIDE TIMING OF HCV THERAPY J. Schulz1 , I.M. Jacobson2,3 , P.Y. Kwo4 , A.J. Muir5,6 , N. Terrault7 , E. King1 , M.S. Sulkowski8 . 1 Clinical Care Options, LLC, Reston, VA, 2 Weill Cornell Medical College, 3 NewYork-Presbyterian Hospital, New York, NY, 4 Indiana University School of Medicine, Indianapolis, IN, 5 Duke Clinical Research Institute, 6 Duke University School of Medicine, Durham, NC, 7 University of California, San Francisco, CA, 8 Johns Hopkins University School of Medicine, Baltimore, MD, United States E-mail: [email protected] Background and Aims: Practice guidelines provide insufficient guidance on timing of HCV therapy, particularly with the rapid evolution of treatment options. We evaluated whether expert recommendations on timing of HCV therapy, delivered via an online decision support tool, would affect management decisions of community practitioners. Methods: 5 HCV experts made recommendations for 900+ patient scenarios. Tool users enter patient liver disease stage, HCV genotype (GT), treatment history, and interferon (IFN) tolerability. Before expert recommendations are revealed, users enter their intended management approach. The tool then displays expert recommendations for the specific patient scenario. Finally, users indicate if the recommendations change or confirm their approach. Results: The tool was posted online in October 2013. 427 cases were entered within 21 days; 41% were real (not hypothetical) patients; 70% were GT 1; 40% had F3/F4 fibrosis, 57% were treatment naive. 18% of users indicated expert recommendations changed their intended management approach. Experts would defer therapy (PR ± BOC or TVR) in all 900+ patient scenarios in favour of future options. By contrast, clinicians planned to start therapy in 45% of cases entered; 33% of those would change plans based on expert recommendations. All experts plan to treat all GT 2 patients once sofosbuvir is available. Recommendations varied most for GT 3 HCV and according to liver disease severity. Additional comparisons of expert and user responses will be presented. Conclusions: Preliminary data indicate an online tool providing customized, patient-specific expert advice may increase the number of clinicians who make optimal decisions regarding timing of treatment for HCV. P775 HEPATITIS C VIRUS INFECTION AND THE ASSOCIATED RISK FOR DIABETES MELLITUS G.T.-W. Shaw1 , M.-H. Lee1,2 , H.-I. Yang1,3 , C.-L. Jen1 , S.-N. Lu4 , L.-Y. Wang5 , S.-L. You1 , G. L’Italien6,7 , Y. Yuan6 , C.-J. Chen1,8 , for the REVEAL-HCV Study Group. 1 Genomics Research Center, Academia Sinica, 2 Institute of Clinical Medicine, National Yang-Ming University, Taipei, 3 Molecular and Genomic Epidemiology Center, China Medical University Hospital, Taichung, 4 Department of Gastroenterology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, 5 MacKay Medical College, Taipei, Taiwan; 6 Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, 7 School of Medicine, Yale University, New Haven, CT, United States; 8 Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan E-mail: [email protected] Background and Aims: The associations between hepatitis C virus (HCV) infection and diabetes mellitus remained inconclusive. The community-based long-term follow-up study aimed to evaluate the relationship between HCV infection and diabetes mellitus by considering conventional risk factors.
Journal of Hepatology 2014 vol. 60 | S215–S359