- Email: [email protected]
P772 CD14+ MONOCYTES AND CD163+ MACROPHAGES CORRELATE WITH THE SEVERITY OF LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C
POSTERS P769 SINGLE NUCLEOTIDE POLYMORPHISMS NEAR IL28B AND IL28A GENES AND RISK OF LIVER CIRRHOSIS AMONG PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION M.-H. Lee1 , H.-I. Yang2 , T.-W. Shaw2 , S.-N. Lu3 , Y.-J. Lin2 , C.-L. Jen2 , Y. Yuan4 , G. L’Italien4 , C.-J. Chen2 , R.E.V.E.A.L.-HCV Study Group. 1 Natioal Yang-Ming University, 2 Genomics Research Center, Academia Sinica, Taipei, 3 Department of Gastroenterology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan; 4 Global Health Economics and Outcome Research, Bristol-Myers Squibb, Princeton, NJ, United States E-mail: [email protected] Background and Aims: The study aimed to evaluate the associations with the development of cirrhosis for the two candidate SNPs (rs8099917 and rs12979860) and other SNPs near IL28A and IL28B genes among patients infected with HCV. Methods: There were 1095 participants seropositive for antibodies against HCV and seronegative for HBsAg in R.E.V.E.A.L-HCV cohort. A total of 72 SNPs near IL28A and IL28B genes were genotyped using Illumina VeraCode GoldenGate genotyping assay. The ascertainment of cirrhosis was by the regular follow-up by ultrasonography and the computerized data linkage with the National Health Insurance database. In addition, the vital status of our study participants was followed by the computerized linkage with the National Death Certification system. All of the participants were followed from 1991 to Dec, 31, 2010. The adjusted hazards ratios (HRadj ) and 95% confidence interval (CI) were estimated by Cox’s regression models. Results: There were 7.9% cirrhosis and 8.5% non-cirrhosis carried TG/GG on rs8099917 (p = 0.84); 9.8% cirrhosis and 10.0% noncirrhosis carried TT or TC on rs12979860 (p = 0.93). There were no additional SNPs near IL28A or IL28B genes associated with cirrhosis. The elevated serum levels of HCV RNA was the strong risk factor for cirrhosis, with the HRadj of 3.28 (1.87–5.75) for low RNA levels and 4.14 (2.42–7.11) for high RNA levels, compared with participants with undetectable RNA (p for trend <0.001). Conclusions: This cohort study showed the SNPs near IL28A and IL28B were not associated with liver cirrhosis risk. However, the increased levels of HCV RNA was the relevant determinants for cirrhosis risk. P770 LOWER UPTAKE OF HCV TREATMENT THAN HIV TREATMENT IN HIV/HCV CO-INFECTED PATIENTS 2 ¨ , A. Blaxhult3 , K. Falconer1 . J. Stenkvist1 , O. Weiland1 , A. Sonnerborg 1 Dep of Medicine, Huddinge, 2 Dep of Medicine, Huddinge and Dep of Laboratory Medicine, Huddinge, 3 Dep of Clinical Science and Education, S¨ odersjukhuset, Karolinska Institute, Stockholm, Sweden E-mail: [email protected]
Background and Aims: HCV co-infection is a leading cause of death in HIV positive patients. Despite a strong indication to treat HCV, treatment uptake is generally lower than in HCV mono-infected patients. Our aim was to determine the HCV and HIV treatment uptake and to define factors associated with initiation or deferral of HCV treatment in Swedish HIV/HCV co-infected patients. Methods: All 5315 adult HIV positive patients in Sweden have been included in the InfCare HIV database. From this database demographic, virologic and treatment data from 652 HIV/HCV coinfected patients were extracted in September 2010. Factors associated with initiation of interferon-based HCV treatment were analysed. In a subgroup, patient- and physicianreported reasons for deferring HCV treatment were investigated. Results: The anti-HCV prevalence was 14% and the chronic HCV infection rate 11%. In total, 25% of HIV/HCV co-infected patients had initiated HCV treatment. HCV genotype 2 or 3, HIV transmission route other than IDU, and on-going HIV treatment were factors
associated with a higher HCV treatment rate. The main reason for not having initiated HCV treatment was IDU or alcohol abuse. Conclusions: The 14% prevalence of anti-HCV noted in Swedish HIV-infected patients was low by international comparisons. The 25% HCV treatment rate noted in our HIV/HCV co-infected patients was high and in the same magnitude of that published in HCV mono-infected patients in Sweden. The HIV treatment rate, however, was considerably higher than the HCV treatment rate. This needs to be improved in the future. P771 HEPCIDIN INVOLVES IN HEPATIC IRON OVERLOAD AND LIVER INJURY IN CHRONIC HEPATITIS C VIRUS INFECTION R. Wang, S. Zhao, J. Du, H. He, P. Tan, Y. Nan. Hebei Medical University, Shijiazhuang, China E-mail: [email protected] Background and Aims: Liver iron overload is a common feature in chronic hepatitis C (CHC). Hepcidin plays a central role in iron homoeostasis. This study aimed to elucidate the role and mechanisms of hepcidin in hepatic iron deposition and liver injury in CHC. Methods: A total of 30 CHC patients and 20 healthy controls were enrolled in the study. Serum levels of hepcidin-25, ferritin, 8-OHdG, IL-6, STAT3 and INF-a were determined by ELISA. The liver histopathological changes were evaluated by H&E and Masson trichromatism staining. The hepatic iron deposition was presented by Perls’ Prussian blue staining. The hepatic expressions of hepcidin-25 and related cytokines were assessed by immunohistochemical staining. Results: Accompanied with liver iron accumulation, low serum level and hepatic expression of hepcidin-25, elevated serum ferritin were observed in CHC patients as compared with the controls (P < 0.01). Serum hepcidin-25 was positively correlated with hepatic hepcidin protein expression in the liver sections, and negatively correlated with serum ferritin, degree of hepatic iron deposition and fibrosis (P < 0.05). Serum levels and hepatic expressions of 8-OHdG and IL-6 were significantly increased, while STAT3 and INF-a were decreased in CHC patients than that in the controls (P < 0.05). Conclusions: Liver iron overload might be associated with hepcidin down-regulation in HCV infection, which could evoke oxidative stress and abnormal iron metabolism, and further induce hepatic inflammation and fibrogenesis. Detection of serum and hepatic hepcidin might be a novel approach for diagnosis of HCV related hepatic iron deposition and liver injury. P772 CD14+ MONOCYTES AND CD163+ MACROPHAGES CORRELATE WITH THE SEVERITY OF LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C S. Zhao, R. Wang, Y. Zhang, P. Meng, L. Kong, Y. Nan. Hebei Medical University, Shijiazhuang, China E-mail: [email protected] Background and Aims: Monocytes and macrophages play an important role in the progression of chronic liver diseases. The study aimed to investigate the significance of mononuclear macrophage and its related cytokines in the progression of chronic hepatitis C (CHC). Methods: A total of 30 CHC patients and 20 healthy subjects were recruited. Liver biopsies were performed and the degrees of hepatic inflammation and fibrosis were graded by Metavir score. Frequencies of total peripheral CD14+ monocytes and expressing IL-2, IL-4, IL-6, IL-8, IL-10, TNFa and IFNg CD14+ monocytes were evaluated by flow cytometry. Hepatic expressions of CD68 and CD163 were examined by immunohistochemical stain. Serum sCD163 level was measured by ELISA.
Journal of Hepatology 2014 vol. 60 | S215–S359
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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
Background and Aims: HCV co-infection is a leading cause of death in HIV positive patients. Despite a strong indication to treat HCV, treatment uptake is generally lower than in HCV mono-infected patients. Our aim was to determine the HCV and HIV treatment uptake and to define factors associated with initiation or deferral of HCV treatment in Swedish HIV/HCV co-infected patients. Methods: All 5315 adult HIV positive patients in Sweden have been included in the InfCare HIV database. From this database demographic, virologic and treatment data from 652 HIV/HCV coinfected patients were extracted in September 2010. Factors associated with initiation of interferon-based HCV treatment were analysed. In a subgroup, patient- and physicianreported reasons for deferring HCV treatment were investigated. Results: The anti-HCV prevalence was 14% and the chronic HCV infection rate 11%. In total, 25% of HIV/HCV co-infected patients had initiated HCV treatment. HCV genotype 2 or 3, HIV transmission route other than IDU, and on-going HIV treatment were factors
associated with a higher HCV treatment rate. The main reason for not having initiated HCV treatment was IDU or alcohol abuse. Conclusions: The 14% prevalence of anti-HCV noted in Swedish HIV-infected patients was low by international comparisons. The 25% HCV treatment rate noted in our HIV/HCV co-infected patients was high and in the same magnitude of that published in HCV mono-infected patients in Sweden. The HIV treatment rate, however, was considerably higher than the HCV treatment rate. This needs to be improved in the future. P771 HEPCIDIN INVOLVES IN HEPATIC IRON OVERLOAD AND LIVER INJURY IN CHRONIC HEPATITIS C VIRUS INFECTION R. Wang, S. Zhao, J. Du, H. He, P. Tan, Y. Nan. Hebei Medical University, Shijiazhuang, China E-mail: [email protected] Background and Aims: Liver iron overload is a common feature in chronic hepatitis C (CHC). Hepcidin plays a central role in iron homoeostasis. This study aimed to elucidate the role and mechanisms of hepcidin in hepatic iron deposition and liver injury in CHC. Methods: A total of 30 CHC patients and 20 healthy controls were enrolled in the study. Serum levels of hepcidin-25, ferritin, 8-OHdG, IL-6, STAT3 and INF-a were determined by ELISA. The liver histopathological changes were evaluated by H&E and Masson trichromatism staining. The hepatic iron deposition was presented by Perls’ Prussian blue staining. The hepatic expressions of hepcidin-25 and related cytokines were assessed by immunohistochemical staining. Results: Accompanied with liver iron accumulation, low serum level and hepatic expression of hepcidin-25, elevated serum ferritin were observed in CHC patients as compared with the controls (P < 0.01). Serum hepcidin-25 was positively correlated with hepatic hepcidin protein expression in the liver sections, and negatively correlated with serum ferritin, degree of hepatic iron deposition and fibrosis (P < 0.05). Serum levels and hepatic expressions of 8-OHdG and IL-6 were significantly increased, while STAT3 and INF-a were decreased in CHC patients than that in the controls (P < 0.05). Conclusions: Liver iron overload might be associated with hepcidin down-regulation in HCV infection, which could evoke oxidative stress and abnormal iron metabolism, and further induce hepatic inflammation and fibrogenesis. Detection of serum and hepatic hepcidin might be a novel approach for diagnosis of HCV related hepatic iron deposition and liver injury. P772 CD14+ MONOCYTES AND CD163+ MACROPHAGES CORRELATE WITH THE SEVERITY OF LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C S. Zhao, R. Wang, Y. Zhang, P. Meng, L. Kong, Y. Nan. Hebei Medical University, Shijiazhuang, China E-mail: [email protected] Background and Aims: Monocytes and macrophages play an important role in the progression of chronic liver diseases. The study aimed to investigate the significance of mononuclear macrophage and its related cytokines in the progression of chronic hepatitis C (CHC). Methods: A total of 30 CHC patients and 20 healthy subjects were recruited. Liver biopsies were performed and the degrees of hepatic inflammation and fibrosis were graded by Metavir score. Frequencies of total peripheral CD14+ monocytes and expressing IL-2, IL-4, IL-6, IL-8, IL-10, TNFa and IFNg CD14+ monocytes were evaluated by flow cytometry. Hepatic expressions of CD68 and CD163 were examined by immunohistochemical stain. Serum sCD163 level was measured by ELISA.
Journal of Hepatology 2014 vol. 60 | S215–S359
S327
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