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Sofosbuvir, ledipasvir in IBD treated patients with advanced biologics including ribavirin eradicating chronic hepatitis C: SOLATAIRE C Trial. A multi-center clinical prospective pilot study
Electronic Poster Abstracts
EP01E-040 TRISULFATE DISACCHARIDE PROTECTS LIVER INJURY SECONDARY TO LIVER ISCHEMIA/ REPERFUSION E. R. Vasques1, J. E. M. Cunha1, A. M. M. Coelho1, S. N. Sampietre1, R. A. Patzina1, H. B. Nader2, I. L. S. Tersariol2, M. A. Lima2, T. Rodrigues3, E. Chaib1 and L. A. C. D’Albuquerque1 1 Gastroenterology (LIM/37), University of Sao Paulo/ Medical School, 2Federal University of Sao Paulo, and 3 Federal University of ABC, Brazil Background: Ischemia and reperfusion (I/R) causes tissue damage and intracellular calcium levels are a factor of cell death. Sodium calcium exchanger (NCX) regulates calcium extrusion and Trisulfated Disaccharide (TD) acts on NCX decreasing intracellular calcium through the inhibition of the exchange inhibitory peptide (XIP). Objectives: The aims of this research are to evaluate TD effects in liver injury secondary to I/R in animals. Methods: Wistar rats submitted to partial liver ischemia were divided in 3 groups: Control: (n = 10): surgical manipulation with no liver ischemia; Saline: (n = 15): rats receiving IV saline before reperfusion; and TD: (n = 15): rats receiving IV TD before reperfusion. Four hours after reperfusion, serum levels of AST, ALT, TNFa, IL-6, and IL-10 were measured. Liver tissue samples were collected for mitochondrial function and malondialdehyde (MDA) content. Pulmonary vascular permeability and histologic parameters of liver were determined. Results: AST, ALT, cytokines, liver MDA, mitochondrial dysfunction and hepatic histologic injury scores were less in TD group when compared to Saline Group (p < 0.05) with no differences in pulmonary vascular permeability. Conclusion: TD decreases liver cell damage, preserves mitochondrial function and increases hepatic tolerance to I/ R injury.
EP01E-041 SOFOSBUVIR, LEDIPASVIR IN IBD TREATED PATIENTS WITH ADVANCED BIOLOGICS INCLUDING RIBAVIRIN ERADICATING CHRONIC HEPATITIS C: SOLATAIRE C TRIAL. A MULTICENTER CLINICAL PROSPECTIVE PILOT STUDY P. P. Basu1, N. J. Shah2, L. Kavali3, M. Aloysius4 and R. Brown Jr.5 1 College of Physicians and Surgeons, Columbia University, 2Liver Transplant Center, University of North Carolina School of Medicine, Carolinas Medical Center, 3 King’s County Hospital Medical Center, 4James J. Peters VA Medical Center, Icahn School of Medicine at Mount Sinai, and 5Weill Cornell Medical College, United States Background: The prevalence and concomitant treatment of chronic HCV and IBD has not been elucidated. IBD and CHC of >20 years duration may have more fibrosis due to immune suppression. Treatment of IBD often requires biological therapies to achieve longer disease-free HPB 2016, 18 (S1), e1ee384
e299
remission, which further accelerates higher HCV replication. Thus effective therapy for IBD patients requiring immunosuppressive therapy is needed. Aim: To evaluate the role and efficacy of new NS5A + NS5B inhibitors with and without RBV in treating CHC in moderate to severe IBD requiring biologic therapy. Methods: 35 patients were recruited from the Kings County Hospital Medical Center, Brooklyn. Inclusion criteria CHC with IBD, Age: >18, HCV Viral Load: > 400,000 IU/mL, Genotype 1. Fibrotic Score: Metavir F1 to F4 Primary End Point: SVR12 Secondary End Point: IBD activity index, sustained control of symptoms SVR 24 and complete IBD remission at 30 weeks (endoscopy at 30 weeks The patients were divided into two groups: Group A (n = 17): RBV 1000 mg + LDV[RB3] and SOF; for 8 weeks Group B (n = 18): LDV and SOF; for 12 weeks Viral loads 0, 7, 14 days; 4th, 8th, 12th and 24th weeks Undetectable
Group A
Group B
Day 7, n, %
12, 70.6%
13, 72.2%
Day 14, n, %
14, 82.3 %
15, 83.3%
Day 28, n, %
16, 94.1% (EOT)
16, 88.9%
8 weeks, n, %
16, 94.1%, SVR 4
17, 94.4%
12 weeks, n, %
–
18, 100%, SVR 4
16 weeks, n, %
16, 94.1%, SVR 12
–
20 weeks, n, %
–
Pending, SVR 12
[Results] Conclusion: This study demonstrates that DAA’s for HCV appear to have similar efficacy and safety in the presence of active IBD therapy with TNF Alfa antagonists while keeping the IBD in uninterrupted remission.
EP01E-043 CHRONIC STRESS DOES NOT IMPAIR LIVER REGENERATION IN RATS K. J. Andersen1, A. R. Knudsen1, O. Wiborg2 and F. V. Mortensen1 1 Department of Surgical Gastroenterology, and 2Institute of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University Hospital, Denmark Background: Although wound healing is a simple regenerative process that is critical after surgery, it has been shown to be impaired under psychological stress. The liver has a unique capacity to regenerate through highly complex mechanisms. The aim of this study was to investigate the effects of chronic stress, which may induce a depression-like state, on the complex process of liver regeneration in rats. Methods: Twenty rats were included in this study. The animals received either a standard housing protocol or were subjected to a Chronic Mild Stress (CMS) stress paradigm. All rats underwent a 70 % partial hepatectomy (PHx). The animals were evaluated on postoperative day 2 or 4. Blood samples were collected to examine circulating markers of inflammation and liver cell damage. Additionally, liver tissues were sampled to evaluate liver weight and regeneration rate.
EP01E-040 TRISULFATE DISACCHARIDE PROTECTS LIVER INJURY SECONDARY TO LIVER ISCHEMIA/ REPERFUSION E. R. Vasques1, J. E. M. Cunha1, A. M. M. Coelho1, S. N. Sampietre1, R. A. Patzina1, H. B. Nader2, I. L. S. Tersariol2, M. A. Lima2, T. Rodrigues3, E. Chaib1 and L. A. C. D’Albuquerque1 1 Gastroenterology (LIM/37), University of Sao Paulo/ Medical School, 2Federal University of Sao Paulo, and 3 Federal University of ABC, Brazil Background: Ischemia and reperfusion (I/R) causes tissue damage and intracellular calcium levels are a factor of cell death. Sodium calcium exchanger (NCX) regulates calcium extrusion and Trisulfated Disaccharide (TD) acts on NCX decreasing intracellular calcium through the inhibition of the exchange inhibitory peptide (XIP). Objectives: The aims of this research are to evaluate TD effects in liver injury secondary to I/R in animals. Methods: Wistar rats submitted to partial liver ischemia were divided in 3 groups: Control: (n = 10): surgical manipulation with no liver ischemia; Saline: (n = 15): rats receiving IV saline before reperfusion; and TD: (n = 15): rats receiving IV TD before reperfusion. Four hours after reperfusion, serum levels of AST, ALT, TNFa, IL-6, and IL-10 were measured. Liver tissue samples were collected for mitochondrial function and malondialdehyde (MDA) content. Pulmonary vascular permeability and histologic parameters of liver were determined. Results: AST, ALT, cytokines, liver MDA, mitochondrial dysfunction and hepatic histologic injury scores were less in TD group when compared to Saline Group (p < 0.05) with no differences in pulmonary vascular permeability. Conclusion: TD decreases liver cell damage, preserves mitochondrial function and increases hepatic tolerance to I/ R injury.
EP01E-041 SOFOSBUVIR, LEDIPASVIR IN IBD TREATED PATIENTS WITH ADVANCED BIOLOGICS INCLUDING RIBAVIRIN ERADICATING CHRONIC HEPATITIS C: SOLATAIRE C TRIAL. A MULTICENTER CLINICAL PROSPECTIVE PILOT STUDY P. P. Basu1, N. J. Shah2, L. Kavali3, M. Aloysius4 and R. Brown Jr.5 1 College of Physicians and Surgeons, Columbia University, 2Liver Transplant Center, University of North Carolina School of Medicine, Carolinas Medical Center, 3 King’s County Hospital Medical Center, 4James J. Peters VA Medical Center, Icahn School of Medicine at Mount Sinai, and 5Weill Cornell Medical College, United States Background: The prevalence and concomitant treatment of chronic HCV and IBD has not been elucidated. IBD and CHC of >20 years duration may have more fibrosis due to immune suppression. Treatment of IBD often requires biological therapies to achieve longer disease-free HPB 2016, 18 (S1), e1ee384
e299
remission, which further accelerates higher HCV replication. Thus effective therapy for IBD patients requiring immunosuppressive therapy is needed. Aim: To evaluate the role and efficacy of new NS5A + NS5B inhibitors with and without RBV in treating CHC in moderate to severe IBD requiring biologic therapy. Methods: 35 patients were recruited from the Kings County Hospital Medical Center, Brooklyn. Inclusion criteria CHC with IBD, Age: >18, HCV Viral Load: > 400,000 IU/mL, Genotype 1. Fibrotic Score: Metavir F1 to F4 Primary End Point: SVR12 Secondary End Point: IBD activity index, sustained control of symptoms SVR 24 and complete IBD remission at 30 weeks (endoscopy at 30 weeks The patients were divided into two groups: Group A (n = 17): RBV 1000 mg + LDV[RB3] and SOF; for 8 weeks Group B (n = 18): LDV and SOF; for 12 weeks Viral loads 0, 7, 14 days; 4th, 8th, 12th and 24th weeks Undetectable
Group A
Group B
Day 7, n, %
12, 70.6%
13, 72.2%
Day 14, n, %
14, 82.3 %
15, 83.3%
Day 28, n, %
16, 94.1% (EOT)
16, 88.9%
8 weeks, n, %
16, 94.1%, SVR 4
17, 94.4%
12 weeks, n, %
–
18, 100%, SVR 4
16 weeks, n, %
16, 94.1%, SVR 12
–
20 weeks, n, %
–
Pending, SVR 12
[Results] Conclusion: This study demonstrates that DAA’s for HCV appear to have similar efficacy and safety in the presence of active IBD therapy with TNF Alfa antagonists while keeping the IBD in uninterrupted remission.
EP01E-043 CHRONIC STRESS DOES NOT IMPAIR LIVER REGENERATION IN RATS K. J. Andersen1, A. R. Knudsen1, O. Wiborg2 and F. V. Mortensen1 1 Department of Surgical Gastroenterology, and 2Institute of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University Hospital, Denmark Background: Although wound healing is a simple regenerative process that is critical after surgery, it has been shown to be impaired under psychological stress. The liver has a unique capacity to regenerate through highly complex mechanisms. The aim of this study was to investigate the effects of chronic stress, which may induce a depression-like state, on the complex process of liver regeneration in rats. Methods: Twenty rats were included in this study. The animals received either a standard housing protocol or were subjected to a Chronic Mild Stress (CMS) stress paradigm. All rats underwent a 70 % partial hepatectomy (PHx). The animals were evaluated on postoperative day 2 or 4. Blood samples were collected to examine circulating markers of inflammation and liver cell damage. Additionally, liver tissues were sampled to evaluate liver weight and regeneration rate.