Srilakshmi Atluri

67 TELAPREVIR WITH ADJUSTED DOSE OF RIBAVIRIN IN NAIVE CHC-G1: EFFICACY AND TREATMENT IN CHC IN HEMODIALYSIS POPULATION. TARGET C (RCT)

PWE-126 Table AVR 1 week VRVR 2 weeks RVR 4 weeks EVR 12 weeks MTVR 18 weeks ETVR 24weeks SVR 48 weeks SVR 60 weeks SVR 72 weeks Group A n=18 SVR 24 weeks VL 820k G1a 8 G1b 7 Il28b CC 5 TT 5 CT 8 10/18(55%) 4/8(50% 6/7(87%) 5/10(50) 1/10(10) 4/10(40) 12/18(67%)

Mo1007 Curcumin, Anti-Oxidant, and Pioglitazone Therapy With Inclusion of Vitamin E in Non Alcoholic Fatty Liver Disease-a Randomized Open Label Placebo Controlled Clinical Prospective Trial (CAPTIVE)

Introduction NAFLD is a global clinical challenge which progresses to cirrhosis and liver cancer. Defective transport of free fatty acids and mitochondrial dysfunction lead to explosion of a series of free radicals, apoptosis, up regulated cytokines and fibrogenesis ultimately causing cirrhosis and cancer. Curcumin is a pan-antioxidant with anti-inflammatory, anti-apoptotic, anti-microbial, and anti-fibrogenic properties. This study evaluates the role of curcumin in NAFLD to progression of NASH Methods Eighty patients (n = 80) with mean BMI 29%, NAFLD score 0.66, NASH fibrotic score 0.33, HOMA IR 3.8, ALT 58, LDLc 143, HDLc 29, Triglyceride 186 and Adipokines ( leptin, Adiponectin, Retinal Binding Proteins) were divided into Group A-(n = 20) pioglitazone 15mg, Group B-(n = 20) vitamin E, Group C-(n = 20) curcumin (all the three above groups received placebo), and Group D (n = 20) vitamin E plus curcumin. Pre and post values (Triglycerides, LDLc, HDLc, ALT, HOMA-IR, TNF-alfa, Leptin, Adiponectin, Retinol Binding Protein, HBA1c, Serum necro-inflammatory NAFLD and NASH fibrotic score were analysed at 3, 6, and 12 months. Diet and exercise were left unchanged. Daily alcohol content was less than 30 grammes Results Group A-Minimal changes on ALT, HbA1c, HOMA, lipids, no changes in TNF-alfa, adipokines, lipid profile and necro-inflammatory score and/or NASH fibrosis score. Group B and Group C had modest changes in ALT, lipid profile, HbA1c and HOMA; while no changes in adipokines, necro-inflammatory score and fibrotic score. Group D had significant changes in all scores particularly the adipokines and small improvements in fibrotic score. All patients tolerated the medications well Conclusion This study postulates the effects of Curcumin plus vitamin E in NAFLD may prevent NASH with a modest anti-fibrotic effects and necroinflammatory score; with impressive changes in adipokines levels. Additive effects of Curcumin with vitamin E has significant effects on Serum lipids and insulin sensitivity. Unavailability of Pre and post liver biopsy was the limitation A large control trial needs to validate. Disclosure of Interest None Declared

358 EFFECT OF N ACETYLCYSTEINE (NAC) IN HYPOXIA INDUCED LIVER INJURY (HILI) – A RANDOMIZED PLACEBO CONTROL CLINICAL TRIAL

day-(21%), 9th day-(36%) and 12th day-(21%). 1/14(7%) died]. B1(CLD)[ LFTs 3rd day-(19%) 6th (44%) 9 th (25%),2/16(6%) died of sepsis] NAC Groups A2[normalised LFTs 3rd (57%)6 th day(43%) 9 th day (25%), (7%)-one died ] B2 (CLD)[Normalized LFTs3 rd day-(63%), 6 th day-(25%) 9 th1/16(6%), one died] Conclusion This Study postulates that IV NAC (A2, B2) has efficient spontaneous recovery and salvage in non-CLD sub group B2 (63%) > A2(57%) in day 3, in CLD NAC (A2) > placebo (A1) clinical recovery over placebo at 3 rd day, (44%) over (36%) - 6 th day. Larger

906 ROMIPLOSTIM'S EFFECT TO OPTIMIZE SVR WITH TELAPRAVIR, RIBAVIRIN, AND PEG INTERFERON-alfa 2a IN THROMBOCYTOPENIC CIRRHOTICS WITH CHRONIC HEPATITIS C. RESTRAINT C- PLACEBO RCT

905 ADHERENCE WITH TELAPREVIR BID vs. q8h DOSING IN TREATMENT-NAIVE HCV-INFECTED PATIENTS: RESULTS FROM THE PHASE III OPTIMIZE STUDY W. Sievert, M. Buti, K. Agarwal, Y. Horsmans, S. Zeuzem, E. Janczewska, L. Nyberg, R.S. Brown Jr., C. Hezode, M. Rizzetto, R. Parana, S. De Meyer, R. De Masi, D. Luo, J. Witek. Monash Medical Centre and Monash University, Melbourne, VIC, Australia; Hospital Valle Hebron and Ciberehd del Instituto Carlos III, Barcelona, Spain; Kings College Hospital at Kings College London, London, UK; Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Brussels, Belgium; Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany; Outpatients Clinic for Hepatology, Myslowice, Poland; Kaiser Permanente, San Diego, CA, Columbia University College of Physicians and Surgeons, New York, NY, USA; Hopital Henri Mondor, Creteil, France; University of Torino, Torino, Italy; Medical School, Federal University of Bahia, Bahia, Brazil; Janssen Infectious Diseases BVBA, Beerse, Belgium; Janssen Research & Development LLC, Titusville, NJ, USA E-mail: william.sievert@monash.edu

PWE-129 Pegylated Interferon Alfa, Nitazoxanide, Telaprevir, Ribavirin, in Genotype 1 Undergoing Prior Experienced Chc-A Randomized Placebo Control Clinical Pilot Trial (Intrigue-C)

Introduction Chronic Hepatitis C is a global challenge with End stage liver disease and rising Hepatocellular Carcinoma. Peg Interferon Alfa and Ribavirin was the backbone of therapy. Recently introduced Directly Acting Antivirals (DAAs)-protease inhibitors have escalated Sustained Viral Response (SVR) in Response guided therapy in non responders, partial responders and relapsers. This study utilised NTZ & Telaprevir; with SOC for 24 weeks in treatment experienced patients. Methods Fifty (n = 50) patients were divided into GroupA (n = 12) NTZ 500 mg three times for 12 weeks, Group B (n = 12) NTZ, BID for 12 weeks Group C (n = 26) control. All received Peg Interferon Alfa 2a 180 mcg SQ QOW with fixed dose of Ribavirin 1200 mg daily for 24 weeks and Telaprevir 750 mg three times daily for 12 weeks. Viral load was obtained at day 0, 7th day, 14thday, 4 weeks, 12th, 24 weeks and 48th weeks SVR. Viral kinetics was analysed. In Group A, B and C: 5/12(42%), 5/12(42%), 10/26(38%) Non Responder, 6/12(50%), 6/12 (50%),4/26(15%) partial responder, and 2/12(16%), 1/12 relapsers (8%), 4/26(15%) relapsers, 2/26(8%) unknown. Use of Growth factors-12% for severe anaemia, 8% for thrombocytopenia and 7% for neutropenia. Skin rash was 29%. Rectalgia was 11%. 3/50(6%) drop out, 2/50(4%) fell in futility law. Exclusion; Decompensated liver disease. HCC, poor controlled DM, severe CAD, Hemolytic anaemia, Major depression, Renal failure, Prior severe skin rash, active drug and alcohol abuse. Results Abstract PWE-129 Table GROUP A GROUP B GROUP C Undetectable 9/12(75%) 10/12(83%) 16/26(62%) NR 1/12 (8%) 2/12 (16%) 4/26 (15%) PR 1/12 (8%) 12/12(100%) 3/26 (11%) AVR 11/12(92%) 12/12(100%) 20/26(77%) VRVR 11/12(92%) 10/12(83%) 22/26(84%) RVR 9/12(75%) 10/12(83%) 18/26(70%) EVR 9/12(75%) 10/12(83%) 16/26(62%) ETVR 9/12(75%) 10/12(83%) 16/26(62%) SVR 8/12(67%) 8/12(67%) 15/26(58%) Conclusion This quadruple 24 weeks regimen has excelled the RVR, EVR, ETVT over SOC with DAAs over 11%, with SVR 67%. Needs a larger trial for validation Disclosure of Interest None Declared.

727 Romiplostim's Effect to Optimize SVR With Telaprevir, Ribavirin, and PEG Interferon-Alfa 2A in Thrombocytopenic Cirrhotics With Chronic Hepatitis C. a Placebo Controlled Prospective Clinical Trial: RESTRAINT C Trial

Introduction Treating HCV cirrhotic patients with thrombocytopenia is challenging, often requiring dose reduction/discontinuation to avoid complications. Significant dose reduction affects response guided therapy (RGT); affecting outcomes. Thrombopoietin (TPO) agonists are used to avoid disruption or therapeutic failure to optimise SVR. This study evaluated the use of TPO agonist in thrombocytopenia in cirrhotics with CHC. Methods Forty five (n = 45) cirrhotic treatment experienced CHC-GT1 patients wererecruited with mean MELD 16, mean platelet count 95. Group A-(n = 15) placebo plus reduced dose of p-IFN with Ribavirin and Telaprevir. Group B (n = 15) Romiplostim 500mcg lead in 1 month prior to initiation of therapy and SOC with Telaprevir. Group C (n = 15) Elthrombopag 50mg orally daily lead in prior 15 days and SOC with Telaprevir for 12 weeks. RGT was analysed with serial platelet counts, haemoglobin/hematocrit, absolute neutrophils count and platelet antibodies. HCV RNA 1ST, 2ND, 4TH, 12TH 24TH, 36TH and 60th weeks for SVR. Results Conclusion This study demonstrates the efficacy of Romiplostim in thrombocytopenic cirrhotics in optimising SVR (Group A-53%, Group B-67% and Group C-60%). A larger trial is needed to validate. Disclosure of Interest None Declared.

Su1697 Restless Leg Syndrome (RLS) Is Associated With Hepatic Encephalopathy (HE) in Decompensated Cirrhosis. a Clinical Pilot Study

Introduction RLS affects 10% of the general population, affecting the quality of life (QOL). Exact aetiology is still unknown. Iron deficiency, small intestinal bacterial overgrowth (SIBO) and inflammatory bowel disease (IBD) have clear association with RLS. Decompensated cirrhosis with portal hypertension has multi-organ involvement causing minimal and overt encephalopathy with sleep: dysnomia, parasomnia, and stupor which has clear association with Sub acute bacterial Peritonitis (SBP ) which has precipitating clinical state with SIBO, This clinical study evaluates the association of RLS in HE amongst decompensated cirrhotics. Methods One hundred eight (n = 108) patients were recruited. Group A (n = 36) decompensated cirrhotic (mean MELD 16, OHE 20/36(55%), MHE 16/36(44%), esophageal varices grade II 24/36(67%). Group B (n = 36) chronic liver disease- Alcohol 9/36(25%) NASH 12/36(33%) HCV 12/36(33%) HBV 1/36(3%) AIH 2/36(6%) with mean MELD 6).without cirrhosis Group C (n = 36) healthy controls. Initially all received Xifaxan 550mg orally twice daily for 10 days to eradicate co-existing SIBO. All underwent Methane breath test for SIBO. Baseline labs: Serum levels for renal function, ferritin, iron studies, haemoglobin/hematocrit, ammonia, celiac, and IBD serology, stool lactoferrin & calprotectin and urine for toxicology screening. Groups A and B underwent neuro-psychometric and flicker testing for MHE and OHE and sleep testing for RLS (with Mayo RLS questionnaire). Exclusion: Chronic iron deficiency, Celiac, IBD, major depression, IBS, benzodiazepines, narcotics, alcohol, anti-psychotics and illicit drugs. Results Group A 24/36(67%) had RLS: [OHE 16/20 (80%), MHE 8/16 (50%), esophageal varices 8/10(80%), alcoholic cirrhotic 10/14(71%), CHC 3/6(50%), NASH 3/6 (50%) and SIBO 14/36 (39%)]. Group B 1/36(3%) RLS and SIBO 7/36(19%). Group C 2/36(6%) RLS and SIBO 3/36(8%). All confirmed by sleep study and RLS questionnaire. Serum ammonia has no impact on RLS. Conclusion This clinical trial postulates decompensated cirrhotics have high evidence of RLS with portal hypertension. Larger trials will validate. Disclosure of Interest None Declared.

Mo1033 Effect of N Acetylcysteine (NAC) in Hypoxia Induced Liver Injury (HILI) - A Randomized Placebo Control Clinical Trial

Introduction HILI is common with a prevalence of 10% in US. Transient shift of intra hepatic hemodynamic compromise leads to tissue hypoxia and induces hypoxia induced protein (HIP), heat shock protein 70 (HSP24.70), Endothelial reticular stress (ER) leading to reperfusion injury (RI). Dramatic rise of transaminases, drastic reversal with restoration of perfusion in weeks follows. In cirrhotics HILI requires liver transplantation. This study evaluated spontaneous recovery and salvage in HILI utilising NAC. Methods Sixty patients (n = 60) with mean arterial pressure (MAP) Exclusions: Organ transplant, Septic shock, Hemodialysis, cancer, acute myocardial Infarct, Tylenol injury, acute viral hepatitis and organ trauma. Results Placebo groups A1, B1: Normalized A1-[LFTs- on 3rd day-(7%), 6th day-(21%), 9th day-(36%) and 12th day-(21%). 1/14(7%) died]. B1(CLD)[ LFTs 3rd day-(19%) 6th (44%) 9 th (25%),2/16(6%) died of sepsis] NAC Groups A2[normalised LFTs 3rd (57%)6th day-(43%) 9 th day (25%), (7%)-one died ] B2 (CLD)[Normalized LFTs- 3rd day-(63%), 6th day-(25%) 9 th1/16(6%), one died] Conclusion This Study postulates that IV NAC (A2, B2) has efficient spontaneous recovery and salvage in non-CLD sub group B2 (63%) > A2(57%) in day 3, in CLD NAC (A2) > placebo (A1) clinical recovery over placebo at 3rd day, (44%) over (36%) - 6th day. Larger trial need to establish the routine usage of IV NAC in HILI. Disclosure of Interest None Declared.