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1042 COMPARISON OF HEPATITIS C DONOR POSITIVE AND HEPATITIS C NEGATIVE GRAFTS IN HEPATITIS C POSITIVE KIDNEY TRANSPLANT RECIPIENTS
POSTERS 1040 OCULAR FINDINGS IN NAIVE HEPATITIS C VIRUS INFECTED SUBJECTS: HIGH PREVALENCE OF OCULAR SURFACE ABNORMALITIES L.P. Zeni1 , O.A. Birkhan1 , M.T. Michalczuk1 , M.A.P. Vilela2 , M. Alvares-da-Silva1 . 1 Universidade Federal do Rio Grande do Sul, Porto Alegre, 2 Universidade Federal de Pelotas, Pelotas, Brazil E-mail: [email protected] Background: Hepatitis C (HCV) infected patients under antiviral treatment are frequently seen in ophtalmological units, mainly due to adverse effects of pegylated interferon. Little is known about ocular changes occurring in naive HCV patients. This study aims to assess the direct influence of the virus in the prevalence of ocular changes in this population. Methods: Monoinfected, naïve, non-obese (BMI < 30), noncirrhotics, non-diabetics HCV patients, aging from 18 to 60 years-old, with no ophtalmological complains, were included, and compared to controls. Patients with previously diagnosed cardiovascular disease, high blood pressure, chronic renal failure, malignancies, abuse of alcohol, pregnancy and those taking chronically lipid lowering drugs or immunossupressve agents, were excluded. Age, BMI, systolic blood pressure, fasting blood glucose, plasma lipid profile, insulin, HCV genotypes and viral load, and liver fibrosis (METAVIR) were determined. Both patients and controls underwent a comprehensive ophtalmological examination, assessing visual function, ocular surface, ocular motility, intraocular pressure, and posterior segment exam. Lacrimal surface was assessed by Schirmer and break up time (BUT) tests. Results: 95 naïve HCV patients and 54 controls were enrolled. HCV patients and controls were similar regarding gender – 47 (49.5%) and 29 (53.7%), respectively (p = 0.74), but HCV were older – 46.6±7.7 years vs 41.3±9.0 (P < 0.001). Only anterior segment abnormalities were found in HCV patients. BUT was more frequently abnormal in HCV patients in comparison to controls (OR adjusted for age = 3.8–95% CI: 1.8–8.0), as well as Schirmer test (OR adjusted for age = 4.2–95% CI: 1.8–9.5), and also biomicroscopy of eyelid (OR adjusted for age = 3.2 95% CI: 1.5–6.9). Genotypes, viral load and fibrosis had no relationship to the findings. Conclusions: We found significant ocular surface and lacrimal abnormalities on a well-selected sample of HCV naïve patients, with low-risk of ophtalmological disease. Given the risk of progression of the ocular disease, these results suggest that is advisable to recommend a specialized ocular evaluation for HCV infected patients, even if asymptomatic. 1041 HCV CORE PROTEIN INDUCES INTRAHEPATIC TGF-BETA ACTIVATION IN TRANSGENIC MICE S. Battaglia1,2 , C. Guettier1,2,3 , N. Benzoubir1,2 , M. Gigou1,2 , D. Samuel1,2,4 , C. Brechot1,2,5 , M.-F. Bourgeade1,2,4 . 1 Unit´e 785, INSERM, 2 UMR-S785, Univ Paris-Sud, Villejuif, 3 Service d’Anatomie Pathologique, AP-HP Hˆ opital de Bicetre, Le Kremlin-Bicˆetre, 4 Centre Hepato-Biliaire, AP-HP Hˆ opital Paul Brousse, Villejuif, 5 Merieux Alliance, Lyon, France E-mail: [email protected] Background: TGF-b is a cytokine involved in the pathologies associated to HCV infection. TGF-b is secreted in a latent, inactive form and its activation is increasingly recognized as a crucial step in TGF-b actions. Active TGF-b exerts a biphasic action during tumor progression, acting as a tumor suppressor at early stages and as an enhancer of invasiveness at later stages. We previously observed that, HCV core protein through impacting TGF-b signalling, alleviated TGF-b-dependent growth inhibition and apoptosis whereas TGF-b was still able to induce an epithelialmesenchymal transition (EMT), a process thought to contribute to the promotion of cell invasion and metastasis. Importantly, we ob-
served that primary cultured hepatocytes expressing HCV core develop an EMT through endogenous TGF-b raising the attractive possibility that HCV core could interfere with TGF-b activation process. Methods and Results: We established transgenic mice expressing HCV core protein and determine active and latent TGF-b in the liver and in the serum of these mice using a bioassay detecting only the active form. We could detect a significant increase of active TGF-b in the liver of core-expressing mice compared to the wild type littermates. Accordingly, we could detect an increase in phospho-Smad2/3 expression in the livers of core expressing mice indicating an active TGF-b signalling. This increase in active TGF-b was not found in the serum suggesting a HCV core-dependent local activation of TGF-b. As already described, HCV core expression was associated with hepatocellular steatosis. Preliminary results from a transcriptional study suggest that HCV core induces TGF-b target genes involved in oxidative stress, which is consistent with the notion that perturbation of lipid metabolism could be mediated by active TGF-b in the livers of mice expressing HCV core. Conclusion: Until now, it was thought that TGF-b effects occurred globally. Our results suggest that TGF-b is active only in a population of cells, driving thus locally the expression of a range of genes. These data strongly argue that HCV core may be related to liver pathogenesis through its ability to induce a local, intrahepatic TGF-b activation and signalling. 1042 COMPARISON OF HEPATITIS C DONOR POSITIVE AND HEPATITIS C NEGATIVE GRAFTS IN HEPATITIS C POSITIVE KIDNEY TRANSPLANT RECIPIENTS R. Battish1 , H. Shah1 , J. Light2 , A. Sherker3,4 . 1 Section of Gastroenterology and Hepatology, 2 Division of Transplant, 3 Center of Liver Diseases, Washington Hospital Center, 4 Georgetown University Medical Center, Washington, DC, USA E-mail: [email protected] Introduction: Kidney transplantation, an effective treatment for end-stage-renal disease (ESRD), is limited by the shortage of available organs. Hepatitis C virus (HCV) infection, the leading cause of liver disease worldwide, is common in ESRD patients. Recipient HCV positive status (HCV R+) in kidney transplant has been associated with poor outcomes compared to HCV negative recipients (HCV R−) including lower survival rates post-transplantation and higher rates of liver complications. However, given the poor outcomes of HCV patients on continuous long-term dialysis kidney transplant is a preferred treatment option. Therefore kidney transplantation from HCV positive donors into HCV positive recipients (HCV D+/HCV R+) has been advocated as a way to expand the donor pool. Aims: To evaluate graft survival from date of transplant and time of listing in HCV D+/HCV R+ and HCV D−/HCV R+ subjects. Methods: A retrospective review of prospectively collected data comparing HCV D+/HCV R+ to HCV D−/HCV R+. There were a total of 76 patients from 2001–2009. 22 were HCV D+/HCV R+ and 37 were HCV D−/HCV R+. 17 were excluded due to unknown HCV donor status. Results: Graft survival from the time of listing was on average longer for HCV D+/HCV R+ (2110 versus 1869 days). Graft survival from date of transplant was on average longer for HCV D+/HCV R+ (1224 versus 1005 days). The maximum time on transplant list for an individual in the HCV D−/HCV R+ group was 1477 days longer than the maximium time for an individual on the HCV D+/HCV R+ group. Conclusion: Results from our retrospective study suggest a trend toward increased graft survival in HCV D+/HCV R+ when compared to HCV D−/HCV R+. Furthermore, graft survival was longer from the time of listing in HCV D+/HCV R+. The utilization of HCV D+ kidney grafts in HCV positive recipients warrants further study.
Journal of Hepatology 2010 vol. 52 | S319–S457
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served that primary cultured hepatocytes expressing HCV core develop an EMT through endogenous TGF-b raising the attractive possibility that HCV core could interfere with TGF-b activation process. Methods and Results: We established transgenic mice expressing HCV core protein and determine active and latent TGF-b in the liver and in the serum of these mice using a bioassay detecting only the active form. We could detect a significant increase of active TGF-b in the liver of core-expressing mice compared to the wild type littermates. Accordingly, we could detect an increase in phospho-Smad2/3 expression in the livers of core expressing mice indicating an active TGF-b signalling. This increase in active TGF-b was not found in the serum suggesting a HCV core-dependent local activation of TGF-b. As already described, HCV core expression was associated with hepatocellular steatosis. Preliminary results from a transcriptional study suggest that HCV core induces TGF-b target genes involved in oxidative stress, which is consistent with the notion that perturbation of lipid metabolism could be mediated by active TGF-b in the livers of mice expressing HCV core. Conclusion: Until now, it was thought that TGF-b effects occurred globally. Our results suggest that TGF-b is active only in a population of cells, driving thus locally the expression of a range of genes. These data strongly argue that HCV core may be related to liver pathogenesis through its ability to induce a local, intrahepatic TGF-b activation and signalling. 1042 COMPARISON OF HEPATITIS C DONOR POSITIVE AND HEPATITIS C NEGATIVE GRAFTS IN HEPATITIS C POSITIVE KIDNEY TRANSPLANT RECIPIENTS R. Battish1 , H. Shah1 , J. Light2 , A. Sherker3,4 . 1 Section of Gastroenterology and Hepatology, 2 Division of Transplant, 3 Center of Liver Diseases, Washington Hospital Center, 4 Georgetown University Medical Center, Washington, DC, USA E-mail: [email protected] Introduction: Kidney transplantation, an effective treatment for end-stage-renal disease (ESRD), is limited by the shortage of available organs. Hepatitis C virus (HCV) infection, the leading cause of liver disease worldwide, is common in ESRD patients. Recipient HCV positive status (HCV R+) in kidney transplant has been associated with poor outcomes compared to HCV negative recipients (HCV R−) including lower survival rates post-transplantation and higher rates of liver complications. However, given the poor outcomes of HCV patients on continuous long-term dialysis kidney transplant is a preferred treatment option. Therefore kidney transplantation from HCV positive donors into HCV positive recipients (HCV D+/HCV R+) has been advocated as a way to expand the donor pool. Aims: To evaluate graft survival from date of transplant and time of listing in HCV D+/HCV R+ and HCV D−/HCV R+ subjects. Methods: A retrospective review of prospectively collected data comparing HCV D+/HCV R+ to HCV D−/HCV R+. There were a total of 76 patients from 2001–2009. 22 were HCV D+/HCV R+ and 37 were HCV D−/HCV R+. 17 were excluded due to unknown HCV donor status. Results: Graft survival from the time of listing was on average longer for HCV D+/HCV R+ (2110 versus 1869 days). Graft survival from date of transplant was on average longer for HCV D+/HCV R+ (1224 versus 1005 days). The maximum time on transplant list for an individual in the HCV D−/HCV R+ group was 1477 days longer than the maximium time for an individual on the HCV D+/HCV R+ group. Conclusion: Results from our retrospective study suggest a trend toward increased graft survival in HCV D+/HCV R+ when compared to HCV D−/HCV R+. Furthermore, graft survival was longer from the time of listing in HCV D+/HCV R+. The utilization of HCV D+ kidney grafts in HCV positive recipients warrants further study.
Journal of Hepatology 2010 vol. 52 | S319–S457
S403