Background: CHC is no longer a clinical challenge in the era of DAA's. CHC and SCD contributes added challenges (sickle cell hepatopathy, splenic dysfunction, accelerated fibrosis secondary to anemia, iron overload and LPS induced mitochondrial injury). Historical management with IFN and RBV causes fatal hemolysis, severe anemia and sepsis. Aim: This study evaluates the safety, efficacy and eradication of hepatitis C in this sub-group population with SCD. Methods: 24 patients were recruited from three sickle cell centers in NYC. Inclusion criteria: CHC (Geno specific with variation, diagnosed between 1998–2014) with SCD in remission (with sickle cell history >30 years). All patients were placed LDV 90 mg + SOF 400 mg a day; with food for 12 weeks. Medications allowed: Hydroxyurea, Tylenol, MS Contin, Methadone, Antibiotics (Levofloxacin, Doxycycline, Colchicine, Metronidazole), epoetin alpha. Exclusion: Decompensated cirrhotics, HIV, HBV, Sepsis, brittle SCD with frequent flares, uncontrolled DM, cardiomyopathy, CHF NYHA class III–IV, CKD, chronic osteomyelitis, active IVDU, Daily alcohol > 30 grams, Deferoxamine for 12 weeks. Side events: Nausea- 9/24, constipation 6/24, diarrhea 2/24, headache 6/24, abdominal pain 3/24, renal colic 1/24, insomnia 8/24, anemia 2/24, hyperbilirubinemia 4/24, UTI 3/24.Tabled 1UndetectableLDV 90 mg and SOF 400 mgDay 7, n, %9/24Day 14, n, %14/24Day 30, n, %22/24Day 60, n , %22/24Day 90, EOT, , n, %22/24Population Viral failure- 1a/4c & 1a/3c8.3% (2/24)Pre and post RAV1/24 (G 1a/4c)Retention100% Open table in a new tab Result Conclusion: This study demonstrates that LDV and SOF combination in SCD patients with CHC is safe and well tolerated; with an SVR12 of 91.67% (22/24) with 8.3% (2/24) viral failure (in concomitant genotypes; 1a/4c and 1a/3c).

Introduction: Acute hepatitis C has been increasing in incidence recently in the USA. Traditional management with peg IFN α2a and weight based RBV has had equivocal success with SVR rates as low as 30% in some studies and considerable side events. Recently oral DAA's have achieved SVR rates exceeding 95% in many cohorts. This clinical pilot study evaluates the efficacy of Sofosbuvir (SOF) with Ledipasvir (LDV) or Simeprevir (SIM) in acute Hepatitis C Methods: 29 patients with a diagnosis of acute hepatitis C (negative past HCV antibody + new onset HCV RNA) were recruited from 6 inner city drug rehab programs in Brooklyn, NY. HIV, HBV, renal insufficiency with CrCl < 40, concomitant drug induced liver injury, active intravenous drug use, alcohol consumption (>50 gms/day), active cocaine or crack use. They were divided into 2 groups; Group A (n=14): SOF 400 mg + LDV 90 mg (daily once) - 4 weeks Group B (n=15): SOF 400 mg + SIM 150 mg (daily once) - 8 weeks Results: See table Conclusion: This study demonstrates a high SVR with short-course DAA's in acute hepatitis C with SVR (at 20 weeks) >90% in both groups. The drugs were well tolerated.Table 1: Results

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.

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

Introduction Thrombocytopaenia is a common entity in CLD with or without cirrhosis. Liver biopsy is the gold standard for diagnosis and prognosis of CLD. Platelet count is imperative before percutaneous liver biopsy. Platelet transfusion requires over night hospitalisation with transfusion associated morbidities and cost burden. Romiplostim, a fusion protein TPO, is a hormone that regulates platelet production approved in idiopathic thrombocytopenic purpura (ITP). This study evaluates single use of Romiplostim 2 week prior to liver biopsy to avoid biopsy related morbidity and mortality. Methods 65 patients (n=65), (mean age: 56 years; M:F-2:1) with Hepatitis C: 37/65 (57%); hepatitis B (HBV) 7 (15.5%), Alcoholic Cirrhosis 10 (15%); Non-Alcoholic steato-hepatits (NASH) 3 (5%), Primary biliary cirrhosis (PBC) 6 (9%) with pre-biopsy mean platelet count 77k; Mean MELD score 20, mode fibrotic score F4 were randomised in blinded fashion into three groups: Group A (n=18), received seven units of platelet transfusion at night for the morning procedure. Group B (n=23) received Romiplostim 500 μg sc given 2 weeks prior to the procedure, and Group C (n=24) Elthrombopag orally 75 mg/day for 2 weeks. PLT-CT was repeated 2 h prior and Post-biopsy in 4 weeks in all groups. Inclusion criteria: CLD with thrombocytopaenia. Results Conclusion This pilot study demonstrates that single use of Romiplostim is efficacious, cost-effective, and safe without side effects for liver biopsy with severe thrombocytopaenia. Single use of Romiplostim should be considered before Trans jugular intra-hepatic porto-systemic shunts or portal haemodynamic procedures and prior to surgical interventions with severe thrombocytopaenia. A large randomised clinical trial is needed for further validation. Competing interests None declared.

POSTERSto the dramatic increase in obesity in many industrialized countries, there is also a dramatic increase in the prevalence of NAFLD and nonalcoholic steatohepatitis (NASH). Aims:i. To define the prevalence of ultrasound-diagnosed NAFLD in large adult general population, ii. to develop a simple algorithm for the prediction of NAFLD using the simplest clinical values, iii. to predict the prevalence of NASH with liver fibrosis utilizing previously established scoring systems.Methods: We studied 9923 individuals (66.1% males) aged 21 to 86 (mean, 49.9) years, who received health-check up from 2009 to 2010 in three health centers in Japan.Fatty liver detected by ultrasound, and individuals with intake over 20-gram alcohol/day or with other chronic liver disease were excluded.Each individual underwent a standard ultrasound, anthropometric and biochemical examination.Variables including sex, age, body mass index (BMI), blood count, alanine transaminase (AST), aspartate transaminase (ALT), gammaglutamyl-transferase (GGT), fasting plasma glucose (FPG), triglycerides, and HDL, LDL-cholesterol were entered into stepwise regression models to obtain the most simple and accurate algorithm for the prediction of NAFLD.Furthermore, we calculated the probability of NASH with advanced fibrosis according to BAAT index, and Fib-4 index.Results: The prevalence of NAFLD was 30.1%.The average prevalence was three-fold higher in males (40.4%) than females (15.3%).The prevalence was equally higher in males than in females in all ages except above the 7th decade.The prevalence was increasingly frequent with age in females.An algorithm based on BMI, AST/ALT, GGT, FPG, hemoglobin, triglycerides, and HDLcholesterol had an accuracy of 79.9% in detecting NAFLD.The estimated prevalence of NASH with septal fibrosis according to BAAT index was 36.3% (BAAT score ≥2), 7.0% (≥3), respectively.The estimated prevalence of NASH with fibrosis according to Fib-4 index was 24.8% (cut off ≥2.67), and 1.8% (≥2.67), respectively.Conclusions: This study revealed that the prevalence of NAFLD was high in general population, especially in males.The prevalence of NASH in NAFLD was estimated to be considerably high in individuals with NAFLD in Japan.

Purpose: Functional bowel syndrome (FBS) is a challenging clinical entity. The etiology is not clear. Disturbed brain-Gut axis with visceral hyperalgia is the mainstay. ROME III criteria establish the diagnosis. Psychological stress, environmental stressor, post-Infection, and tight junction dysfunction have been implicated. Mast cell postulates immune etiology in FBS. Extral-luminal manifestations, such s Urinary frequency, urgency, pressure and pain is a part of FBS. Interstitial Cystitis (IC) is a part of FBS This study evaluates the urodynamic changes of IBS in FBS. Methods: Fifty-Two (n=52) patients with Irritable Bladder symptoms were recruited from age 23 - 67 (mean 47)-Female 25(48%), Male 27(52%); divided into Group A(n= 13) control, Group B(n=39) ROME III proven FBS with urinary urgency, frequency, pain and pressure symptoms. Group B (Female-30/39(77%); Male 9/39 (23%)-(Female:Male ratio 3:1))further subdivided into 13/39 (33%) Diarrheal, 13/39(33%) mixed and 13/39(33%) Constipation type. All underwent stool and blood for infections, inflammatory bowel disease, celiac diease, with colonoscopy biopsies. Group B, 21/39(53.8%) all underwent bladder biopsy. Results: IBS has Altered Urodynamic with change of compliance with normal pressure manometry (p=0.0003) and MUCP (p=0.03) over controls, but no differences in Maximum flow (p = 0.12) and Maximum pressure flow (p = 0.30) between groups. See Table 1.Table 1: ResultsConclusion: This study demonstrates altered compliance in irritable bladder syndrome reflecting a strong correlation with functional bowel syndrome. A larger study is needed to validate the hypothesis.

Purpose: CDAD is a growing clinical challenge in the U.S. Emerging drug resistance is the primary cause of treatment failure causing recurrence. Oral Vancomycin and Metronidazole are the approved therapies. “Turmeric” has been used over centuries in Eastern culture and medicine. It is an antioxidant, anti-ulcerogenic, anti-inflammatory and antimicrobial agent. Turmeric enema has been used in Ulcerative colitis. This clinical trial evaluates the role of turmeric enema in moderate to severe community acquired CDAD. Methods: Thirty-six patients(n=36); mean age of 53 years with moderate to severe CDAD were randomized into three groups: Group A-Placebo(n=11), Group B-Vancomycin enema (n=12) -250mg BD, and Group C-Turmeric enema (n=13), 1gm twice daily for 10 days. All patients received oral metronidazole 500mg thrice daily for 14 days. ATLAS score for clinical severity, stool for C. difficile toxin A/B were measured initially and at the end of therapy. Flexible sigmoidoscopy was performed, pre- and post-therapy after 21 days. Multivariate analysis was obtained among all the groups with clinical score, endoscopic appearance and cost. Results: All patients tolerated the enemas well except Group C with complaints of staining of fomites. 7/11 (66%) in group A compare to 10/12 (83%) in group B, and 10/13 (76%) in group C eradicated the infection. Groups B and C had reduced ATLAS score and endoscopic score of 60% compared to Group A's 38%. The recurrence rate was lower in both Group B-1/10 (10%) and Group C-1/11 (9%) over placebo-2/7 (29%). Post-treatment endoscopic appearance of luminal ulcers with Vancomycin (p=0.037) and Turmeric (p=0.031) compared with the Placebo had a significant difference. Post treatment mucosal bleeding was statistically significant in Turmeric (p =0.001) to vanco (p=0.027). Conclusion: This study demonstrates no significant difference between Turmeric and Vancomycin enema in moderate to severe CDAD. Patient tolerated both enemas with significant cost benefit in turmeric over Vancomycin. A larger control trial is necessary to validate the efficacy.

Purpose: Vancomycin and metronidazole are currently the recommended therapies for CDI. Treatment failure is due to increasing antimicrobial resistance, insufficient length of therapy, and suboptimal drug exposure. Recurrence is estimated up to 20-50% in susceptible populations. We utilize a novel sequential nitazoxanide treatment for 28 days for recurrent CDI. Methods: Thirty (n=30) patients (age: 57.9±8.1 years; 13 non-hospital and 17 hospital acquired) were treated with oral vancomycin or metronidazole for 14 days and had recurrent CDI within 60 days posttreatment. All patients had abdominal pain, fever, diarrhea >3 times/day, leukocytes >12,000, and positive stool toxin assay with Elisa A/B. All were randomized into two groups: Group A (n=15) patients received nitazoxanide 500 mg BID for 14 days, followed by 250 mg BID for 7 days, followed by 125 mg BID for 7 days; Group (n=15) received vancomycin 250 mg QID for 14 days, followed by 250 mg BID for 7 days, followed by 125 mg BID for 7 days. Exclusion criteria: sepsis, toxic megacolon, inflammatory bowel disease, celiac disease, other colitidies, renal sufficiency, probiotic use, immunocompromised state, hemodialysis, or recent chemotherapy. Results: Stool assay PCR for CDI was negative in 10/15 (66.7%) patients after sequential nitazoxanide treatment and in 11/15 (73.3%) patients with sequential vancomycin therapy. There was no significant difference (p=0.99, Fisher's exact test) in fecal eradication rate of CDI between the two treatment groups. Side effects with nitazoxanide treatment were minimal including nausea (n=3), vomiting (n=1), constipation (n=4), bloating (n=2), loss of appetite (n=5), and yellow skin color (n=3). This was comparable to vancomycin. Conclusion: This novel sequential therapy with nitazoxanide shows a comparable cure rate to sequential oral vancomycin treatment for recurrent CDI. Nitazoxanide has an advantageous cost benefit over oral vancomycin with minimal side effects. A larger, double-blinded clinical trial is warranted for validation.

April 25 metabolic parameters in patients with MS.We describe a case series using Rimonabant in biopsy-proven NASH patients and its results.Seven patients presenting with metabolic syndrome and elevated ALT underwent liver biopsy between April and July, 2008.All of them had biopsy-proven NASH according to Brunt classification.There were 5 women and 2 men in this series.To all of them was prescribed Rimonabant 20 mg qd.The baseline characteristics are as follows: mean age of 48.4 years; weight of 93.5(±15.6)kg; abdominal girth of 102.2(±11.3)cm, BMI of 33.4(±2.15)kg/m 2 , LDL cholesterol of 131.1(±19) mg/dL, fasting glucose of 100.7(±7.4)mg/dL, triglycerides of 177.4(±31.2) mg/dL, ALT of 84.1(±17.3)UI/mL.The average elapsed time on medication was only 3.7 months because Rimonabant withdrawal from the market by the regulatory agencies.Post-drug values were as follows: weight of 87.6(±15.1)kg; abdominal girth of 98.4(±10.8)cm; BMI of 31(±1.8)kg/m 2 , LDL cholesterol of 105.8(±33.1),fasting glucose of 96(±5.3)mg/dL, triglycerides of 150.2(±22.4)mg/dL and ALT values of 38.8(±10.2) UI/mL The only related adverse effect observed was dry mouth in one patient.No depression or any other psychiatric sign or symptom was observed.Pre-treatment Post-treatment P-value ALT 84.1 38.8 <0.005 Abdominal girth 102.2 98.4 <0.005 BMI 33.4 31 <0.005Fasting glucose 100.7 96 0.006 Weight 93.5 87.6 <0.005 LDL cholesterol 105.8 131.1 0.03 Triglycerides 177.4 150.2 0.001 Conclusion:In this series of biopsy-proven NASH there was a significant improvement in all parameters evaluated with Rimonabant treatment, including ALT level, without any relevant drug related side effect.

Purpose:Heliobacter pylori (HP) gastritis and peptic ulcer disease are global threats for gastric carcinoma including MALT tumors and pancreatic cancer. The WHO has even classified HP as a type 1 carcinogen. Multiple therapeutic regimens have been explored to eradicate HP with variable success rates due to progressive drug resistance and virulent bacterial gene expression (CagA type). For example, metronidazole and clarithromycin are considered the “backbone” of most HP regimens, however in vitro resistance to these antibiotics has been reported to be as high as 40% and 13% respectively. In addition, tolerability and patient compliance with these regimens can be problematic. This study evaluates a quadruple drug regimen, three antibiotics and a proton pump inhibitor (PPI), for the eradication HP in patients that have previously failed therapy. Methods: Thirty (N = 30) patients whom had previously failed an HP regimen (ages 20–65) with diverse ethnicity and demographics were evaluated. The previous regimens included: 9 (30%) failed rifaximin, omeprazole and levofloxacin (ROL) therapy, 10 (33.33%) failed lansoprazole, amoxicillin, and clarithromycin therapy (LAC), 1 (3.3%) failed rifabutin, amoxicillin and pantoprazole therapy (RAP) and 10 (33.33%) patient regimens were not fully identified. The diagnosis of HP gastritis or peptic ulcer disease was made using endoscopy and stool antigen testing. All patients were given LEND therapy (Levofloxacin 250 mg with breakfast, Esomeprazole 40 mg before breakfast, Nitazoxanide 500 mg twice daily with meals and Doxycycline 100 mg at dinner) for a total of 10 days with a wash out time of 6 weeks from any prior antibiotic or PPI use. HP eradication was confirmed by stool antigen testing 2 weeks after cessation of therapy (Quest Laboratory, Teterboro, NJ). Patients with active gastrointestinal bleeding, on non steroidal anti-inflammatory drugs, warfarin and histamine-2 receptor blockers were excluded from the study. Results: In an intent to treat analysis, the eradication of HP was documented in 27/30 (90%) patients. The three failures were in patients that did not complete the full course of therapy, 2 (6.7%) complained of nausea and abdominal bloating with irregular bowel pattern and 1 (3.3%) stopped therapy due to non-specific itching that resolved without medical intervention. Overall the regimen was well-tolerated. Conclusion: This open label prospective trial demonstrates that LEND (Levofloxacin, Esomeprazole, Nitazoxanide, and Doxycycline) is a highly active regimen for the treatment of Heliobacter pylori in patients that have previously failed therapy. A large randomized controlled clinical trial will further establish the therapeutic superiority of this regimen.

Twenty-one patients with corrosive esophageal strictures underwent contrast-enhanced CT of the chest to determine (1) the esophageal wall thickness at the stricture site and (2) its correlation with number of sessions required for adequate dilation. Average esophageal wall thickness was defined as the mean thickness of all four walls at the site of the stricture, whereas the size of the thickest wall was taken as maximal esophageal wall thickness. Average esophageal wall thickness (8.52 +/- 0.61 mm; range, 5.4 to 13.5 mm) and maximal esophageal wall thickness (11.63 +/- 0.83 mm; range, 5.4 to 20 mm) were significantly higher in patients with corrosive esophageal strictures than normal esophageal wall thickness (2.70 +/- 0.04 mm, p < .01). These patients required a mean of 5.70 +/- 1.42 sessions for achieving adequate dilation. Age, sex, grade of dysphagia, and cause and site of the stricture did not influence the number of sessions required for adequate dilation. On multivariate analysis, maximal esophageal wall thickness (p < .01) but not average esophageal wall thickness or stricture length was independently associated with the number of sessions required for adequate dilation. Patients with maximal esophageal wall thickness of 9 mm or more required a significantly higher number of sessions for adequate dilation than did those with wall thickness of less than 9 mm (7.57 +/- 1.80 versus 1.42 +/- 0.27, p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)