Niraj J. Shah

A Randomized Study Comparing Levofloxacin, Omeprazole, Nitazoxanide, and Doxycycline versus Triple Therapy for the Eradication of Helicobacter pylori

OBJECTIVES:Resistance to standard Helicobacter pylori (HP) treatment regimens has led to unsatisfactory cure rates in HP-infected patients. This study was designed to evaluate a novel four-drug regimen (three antibiotics and a proton pump inhibitor (PPI)) for eradication of HP infection in treatment-naive patients.METHODS:Patients with a diagnosis of HP gastritis or peptic ulcer disease confirmed using endoscopy and stool antigen testing were eligible for inclusion in this study. All patients underwent a washout period of 6 weeks from any prior antibiotic or PPI usage. Patients were then randomized to either levofloxacin, omeprazole, nitazoxanide, and doxycycline (LOAD) therapy for 7 days (LOAD-7) or 10 days (LOAD-10), including levofloxacin 250 mg with breakfast, omeprazole 40 mg before breakfast, nitazoxanide (Alina) 500 mg twice daily with meals and doxycycline 100 mg at dinner, or lansoprozole, amoxicillin, and clarithromycin (LAC) therapy for 10 days, which included lansoprozole 30 mg, amoxicillin 1 g with breakfast and dinner, and clarithromycin 500 mg with breakfast and dinner. HP eradication was confirmed by stool antigen testing at least 4 weeks after cessation of therapy.RESULTS:Intention-to-treat analysis revealed significant differences (P<0.05) in the respective eradication rates of the LOAD therapies (88.9% (80/90) LOAD-10, 90% (81/90) LOAD-7, 89.4% (161/180) for combined LOAD) compared with those receiving LAC, 73.3% (66/90). There were no differences in adverse effects between the groups.CONCLUSIONS:This open-label, prospective trial demonstrates that LOAD is a highly active regimen for the treatment of HP in treatment-naive patients. A large randomized controlled trial is warranted to further evaluate the efficacy of this regimen.

Rifaximin therapy for metronidazole-unresponsive Clostridium difficile infection: a prospective pilot trial

Background: Clostridium difficile infection (CDI) is a recent epidemic in the United States, particularly in the hospital setting. Oral metronidazole is standard therapy for C. difficile infection, but resistance to metronidazole is becoming a clinical challenge. Methods: We evaluated the efficacy of the nonsystemic oral antibiotic rifaximin for the treatment of metronidazole-resistant C. difficile infection. Twenty-five patients with C. difficile infection were enrolled in the study. All had mild-to-moderate C. difficile infection (5—10 bowel movements a day without sepsis) unresponsive to metronidazole (i.e. stools positive for toxins A and B after oral metronidazole 500 mg three times daily [t.i.d.] for 5 days). After discontinuation of metronidazole, rifaximin 400 mg t.i.d. for 14 days was prescribed. Patients were followed for 56 days and stool was tested for C. difficile using polymerase chain reaction (PCR) to assess the effect of treatment. A negative PCR test result was interpreted as a favorable response to rifaximin. Results: Sixteen of 22 patients (73%) were eligible for study inclusion and completed rifaximin therapy experienced eradication of infection (stool negative for C. difficile) immediately after rifaximin therapy and 56 days post-treatment. Three patients (12%) discontinued therapy because of abdominal distention. Rifaximin was generally well tolerated. Conclusions: In conclusion, rifaximin may be considered for treatment of mild-to-moderate C. difficile infection that is resistant to metronidazole. Larger randomized trials are needed to confirm these positive findings.

Review article: the endocannabinoid system in liver disease, a potential therapeutic target

Endocannabinoids are a family of potent lipid‐soluble molecules, acting on the cannabinoid (CB) receptors that mediate the effects of marijuana. The CB receptors, endocannabinoids and the enzymes involved in their synthesis and degradation are located in the brain and peripheral tissues, including the liver.

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%)

Clinical and Neurologic Manifestation of Minimal Hepatic Encephalopathy and Overt Hepatic Encephalopathy

Hepatic encephalopathy (HE) shows a wide spectrum of neuropsychiatric manifestations. A combined effort with neuropsychological and psychometric evaluation has to be performed to recognize the syndrome, whereas minimal HE (MHE) is largely under-recognized. Subtle symptoms of MHE can only be diagnosed through specialized neuropsychiatric testing. Early diagnosis and treatment may drastically improve the quality of life for many cirrhotic patients. Further research to gain better insight into the pathophysiology and diagnostic accuracy of HE will help determine future management strategies.

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

P528 RESTLESS LEG SYNDROME (RLS) IS ASSOCIATED WITH HEPATIC ENCEPHALOPATHY (HE) IN DECOMPENSATED CIRRHOSIS. A CLINICAL PILOT STUDY

Objective: The prevalence of RLS is close to 10% in the general population; which adversely affects the quality of life (QOL). Exact etiology of RLS is still unknown. Iron deficiency, small intestinal bacterial overgrowth (SIBO) and inflammatory bowel disease (IBD) have clear associations with RLS. Decompensated cirrhosis with portal hypertension has multiorgan involvement causing minimal and overt encephalopathy, sleep disturbances ( dysnomia, parasomnia) and stupor; all of which has a clear association with sub acute bacterial peritonitis ( SBP ) which has a precipitating clinical state along with SIBO. This clinical study evaluates the association of RLS in HE amongst decompensated cirrhotics. Methods: One hundred and eight (n=108) patients were recruited and subdivided into three subgroups. Group A (n=36) decompensated cirrhotic (mean MELD of 16, OHE 20/36 (55%), MHE 16/36 (44%), esophageal varices grade II 24/36 (67%). Group B (n=36) chronic liver disease without cirrhosis with mean MELD 6: Alcohol related 9/36 (25%), NASH 12/ 36 (33%), HCV 12/36 (33%), HBV 1/36 (3%) and AIH 2/36 (6%). Group C (n=36) healthy controls. Initially all received Xifaxan 550mg orally twice daily for 10 days to eradicate coexisting SIBO. All underwent Methane breath test for SIBO. Baseline labs: Serum levels for renal function, ferritin, iron studies, hemoglobin and hematocrit, ammonia, Celiac and IBD serology, stool lactoferrin & calprotectin and urine for toxicology screening were collected. 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 disease, IBD, major depression, IBS, benzodiazepines, narcotics, alcohol, anti-psychotics and use of 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 individuals were confirmed by sleep study and RLS questionnaire. Serum ammonia has no impact on RLS. Conclusion: This clinical trial postulates that decompensated cirrhotics with Hepatic encephalopathy have high incidence of RLS with portal hypertension. Larger trials will validate this finding.

838 Pegylated Interferon Alfa, Nitazoxanide, Telapravir, Ribavirin, in Genotype 1 Undergoing Prior Experienced Chronic Hepatitis C Patients-a Randomized Placebo Control Clinical Pilot Trial (I N T R I G U E C) Interim

Introduction Chronic hepatitis C is a global challenge with end stage liver disease and rising Hepatocellular Carcinoma. Peg Interferon α and Ribavirin was the backbone of therapy. Recently introduced Directly Acting Antivirals -protease inhibitor has a promising role in escalating Sustained Viral Response in Response guided therapy in non-responders, partial and relapses. This study utilised Nitazoxanide (NTZ) and Telapravir, with SOC for 24 weeks in treatment experienced patients. Methods 50 (n=50) patients were divided into Group A (n=12) NTZ 500 mg three times for 12 weeks, Group B (n=12) NTZ 500 mg twice daily for 24 weeks Group C (n=26) control. All received Peg Interferon α 2a 180 μg SQ QOW with fixed dose of Ribavirin 1200 mg daily for 24 weeks with Telapravir 750 mg three times daily for 12 weeks. Viral load was obtained at day 0, 7th day, 14th day, 4 weeks, 12th week and 24 weeks. Viral kinetics was analysed. In Group A: 5/12 (42%) Non-Responder, 6/12 (50%) partial responder, 2/12 (16%) relapsers. In Group B: 5/12 (42%) Non-responders, 6/12 (50%) partial responder, 1/12 relapsers (8%). In Group C: 10/26 (38%) non-responder, 10/26 (38%) partial responder, 4/26 (15%) relapsers, 2/26 (8%) unknown. Exclusion: Decompensated Cirrhotic, HCC, poor DM, Haemolytic Anaemia, Severe Coronary artery disease, major depression, renal failure, Prior severe skin rash, active drug and alcohol abuse. Side Effects: Anaemia 28/50 (56%), Neutropenia 14/50 (28%), Thrombocytopaenia 8/50 (16%), Fatigue 34/50 (68%), Depression 10/50 (20%), Mild skin rash 22/50 (44%), Severe skin rash 1/50 (2%). Use of Growth factors: Epogen 12/50 (24%) Neupogen 8/50 (16%) Elthrombopag 5/50 (10%). Results Conclusion This quadruple truncated regimen has excelled the RVR, ETVR over SOC with Directly Acting Antivirals over 13%, without any difference between 24 weeks of NTZ over 12. Needs a larger trial for validation. Competing interests None declared.

242 EFFECT OF HIGH-DOSE RIBAVIRIN (RBV), ALINIA (NITAZOXANIDE) AND PEGYLATED INTERFERON (PEGIFN) ALFA-2A IN ATTAINING SUSTAINED VIROLOGIC RESPONSE (SVR) IN TREATMENT OF CHRONIC HEPATITIS C

241 REDUCING ALPHA-FETOPROTEIN WITH INTERFERON THERAPY SUPPRESSES HEPATOCARCINOGENESIS IN HEPATITIS C VIRUS-INFECTED PATIENTS WHO ARE VIROLOGICAL RESPONDERS AND NON-RESPONDERS Y. Asahina, K. Tsuchiya, N. Tamaki, M. Sato, T. Tanaka, I. Hirayama, Y. Yasui, K. Ueda, T. Kuzuya, H. Nakanishi, J. Itakura, M. Kurosaki, N. Izumi. Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan E-mail: asahina@musashino.jrc.or.jp

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