Patrick Basu

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.

Prevalence of restless legs syndrome in patients with irritable bowel syndrome

AIM To determine the prevalence of restless legs syndrome (RLS) in patients with irritable bowel syndrome (IBS). METHODS Patients with diarrhea-predominant IBS (n = 30), constipation-predominant IBS (n = 30), or mixed-symptom IBS (n = 30) were recruited from the community between March 2008 and February 2009. Rifaximin 200 mg three times daily was administered empirically to alleviate small intestinal bowel overgrowth in all patients. The presence of RLS was assessed via an RLS questionnaire and polysomnography. RESULTS Twenty-six patients with IBS (29%) were diagnosed with RLS using the RLS questionnaire. Twenty-four of the 26 patients (92%) underwent polysomnography, and all had confirmation of RLS. A greater percentage of patients with RLS had diarrhea-predominant IBS (62%) compared with patients with constipation-predominant IBS (4%) or mixed-symptom IBS (33%). CONCLUSION Restless legs syndrome is prevalent in patients with IBS, especially those with diarrheal symptoms. Assessment of concomitant disorders may improve diagnosis and expand relevant treatment options for patients.

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.

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

Sa1074 Effects of Lidocaine 3% Gel Delivered Rectally in Ano Rectal Dysfunction (ARD) Induced by Telaprevir Therapy in Chronic Hepatitis C-a Randomized Placebo Control Study

Introduction Telapravir is a Potent Protease Inhibitor, which causes anorectal dysfunction (ARD) comprising Proctalgia, Rectal Ulcers, Hemorrhoids and rectal bleeding. Conventional therapy is suboptimal causing treatment Failure. This study evaluates 3% Topical Lidocaine gel rectal delivery to abate the drug related ARD to avoid treatment failure. Methods 52 Patients (mean age 51) were recruited undergoing therapy with Telapravir, Peg Interferon and Ribaviran for CHC-C. 45/52 (86%), with Rectalgia, 8/52 (15%) rectal ulcers, Hemorrhoids 19/52 (36%) with bleeding 6/19 (31%) without Bleeding 13/19 (68%). Group A (n=17) placebo Group B (n=17) hydrocortisone 2.5% Cream and Group C (n=18) Lidocaine 3% Gel foam per rectally twice daily. All underwent Pre and post Proctoscopic evaluation and Ano-rectal manometry. Results Conclusion Results: Rectalgia resolved in 3/17 (17%), 8/17 (47%) and 7/18 (94%) for Group A, B and C respectively. Rectal ulcers healed in 0/2 (0%), 1/3 (33%) and 2/3 (66%) for all the above groups. Hemorrhoids resolved in 1/6 (16%), 2/6 (33%) and 5/7 (71%) in all groups. Pre/Post Proctoscopy revealed normal mucosal integrity 4/17 (23%), 7/17 (41%) and 17/18 (94%) above groups. Results of Pre/Post Rx mean scores for pain, Itching and Burning shown on (Abstract PMO-168 table 3). AR Manometry results showed Pre/Post treatment high sphincter tone >4 mm in Group A 2/15 (8%) and no differences in pre and post treatment, Group B 7/15 (41%), 4/15 (22%) and Group C 5/15 (20%), 2/15 (10%) respectively (Abstract PMO-168 table 4). Side events; Numbness, 4/17 (23%) in lidocaine. Conclusion: Rectally delivered Lidocaine 3% gel is efficacious, tolerable compared to the SOC and placebo for ARD causing treatment failure, retention and SVR. Larger trial needs to validate this finding. Competing interests None declared.

Mo1910 Prevalence of Hepatitis E in New York Among HIV Negative Chronic Liver Disease Population “Is it an Innocent Bystander”

Introduction Hepatitis E is essentially an oral fecal infection with high prevalence in developing countries. There is limited data available on its prevalence in Urban US. The study evaluates the prevalence of hepatitis E antibody IgG and IgM in New York in patients with chronic liver disease. Methods 440 (n=440) were divided into two groups: group A; control 140 patients without any stigmata of liver disease. Group B, 300 patients with history of liver disease including hepatitis B 125/300 (41%), Chronic hepatitis C 60/300 (20%), fatty liver 70/300 (23%), Alcoholic liver disease 29/300 (10%), HBV HCV co infection 9/300 (3%), auto immune hepatitis 2/300 (0.6%), PBC /PSC 5/300 (2%). HEV antibody IGM and IGG were measured with HEV genotyping. 22/300 (7%) patients were liver transplant recipients, 6/300 (2%) patients were kidney transplant recipients. 43/300 (14%) patients were Intra venous Drug Abuser. 20/300 (7%) received Blood products. Results History and genotypic characteristics Conclusion Results : Group (A) HEV IgG positive 13% (18/140), Group B HEV IgG positive 40.6% (122/300) including 3.7% (4/122) having both IgM and IgG positive. The prevalence of HEV IgG was 54% (12/22) in the liver transplant recipient group and 33% (2/6%) kidney transplant recipient group. The study demonstrates the prevalence of hepatitis E infection in New York and HEV antibody in CLD. Including transplant donors and recipients. Question remains the impact and progression of acute or chronic liver disease with concomitant HEV in pre, peri, and post liver transplant recipient. Larger study needs to validate. Competing interests None declared.

Effects of Interferon Alpha on Parathyroid Gland in Chronic Hepatitis B and C: An Observational Study

Introduction: Serum alanine aminotransferase (ALT) remains one of three principal parameters used by AASLD, EASL, and APASL guidelines to identify candidates for antiviral therapy. Whereas individuals who are immunotolerant or inactive carriers can be safely monitored, and individuals with immune active disease clearly warrant antiviral therapy, individuals with elevated HBV DNA but normal ALT represent a subgroup for whom treatment remains controversial. Aim: We conducted a systematic review and meta-analysis to evaluate the prevalence of significant histology (grade 2 activity or stage 2 fibrosis) in individuals with chronic HBeAg positive or negative infection, elevated HBV DNA, and persistently normal serum ALT, defined as at minimum two consecutive normal values based on laboratory reference range or standarized Prati criteria six months apart. Methods: Searches of literature databases and meeting abstracts 2000-2010 were performed by two independent reviewers through September 2010. Observational studies with at least 30 patients who underwent a liver biopsy within six months of index serum ALT were included. After adjudication of a third expert reviewer, nine studies meeting quality criteria were identified, including 849 patients. Results: Pooled analyses revealed that the prevalence of significant histologic disease was 22.5% overall, 12.2% in HBeAg+ patients, and 23.7% in HBeAgpatients. Additional predictors of significant histology included HBV DNA, definitions of normal serum ALT, and number of normal serum ALT values. Conclusions: A significant proportion of patients with persistently normal serumALT and high HBVDNAhave histologic evidence of significant disease, and may represent potential candidates for antiviral therapy. Additional studies to clarify individuals to be targeted for liver biopsy and antiviral therapy in this setting are warranted.

Serum Retinol Binding Protein 4 (RBP-4) is a Unique Surrogate Marker of END Stage Liver Disease With Complications. A Pilot Clinical Trial

Background: Retinol binding protein 4 (RBP-4), a 21 kilodalton plasma protein, is secreted from the liver and adipose tissue, and is known to transport retinol in the blood. RBP-4 levels have an inverse relationship with disease progression and decompensation. This study evaluates the role of RBP-4 on assessing the severity of decompensated liver disease Methods: 85 patients (n=85) (age=49.6±11.4, mean±SD) with moderate to -severe liver disease (mean MELD of 18) were recruited into three groups: Group AChronic liver disease with cirrhosis (n=30):20/30 HCV (67%) 8/30 HBV (27%) 2/30 Misc (6.6%) with mean MELD of 22; Group Bnon-cirrhotic (n=30) 13/20 HCV (43%), 4/20 HBV (13.3%), 5/30 Alcoholics (17%), and 5/30 misc (17%) with mean MELD of <10 Group Ccontrols (n=25) with MELD <10, Liver biopsy, insulin resistance (HOMA-score), MELD score, adiponectin, Leptin and serum RBP-4 (ELISA), APRI, Hyaluronic acid, and Hepascore for liver fibrosis were analyzed Results: There was a significant difference in RBP-4 across the cirrhotic, non-cirrhotic, and control groups (F(2, 82)=47.9, p<0.001; one-way ANOVA). Posthoc Bonferroni tests over controls (n=25, 4.21+/1.60; mean+/-SD). RBP4 is significantly decreased in Cirrhotics (p<0.001; n=30, 1.46+/0.51) over the non-Cirrhotics (p=0.015; n=30, 3.37+/0.97) and controls. Cirrhotics also had decreases in HOMA (1.09±0.09 vs. 1.51±0.60; p=0.001, Students t-test),adiponectin (0.93±0.40 vs. 1.26±0.53; p=0.01), but with an increase in TNFalpha (11.23±3.81 vs. 3.72±3.37; p<0.001) compared to the non-cirrhotic patients. Leptin (8.20±3.23 vs. 10.93±9.44; p=0.14) and hepatic steatometry (BURNT score<4)-(0.73±0.83 vs. 1.10±1.21; p=0.19 showed no difference. RBP 4 has no relevant correlations with TNFalpha (r=-0.62, p<0.001), leptin (r=0.12, p=0.38) and hepatic steatometry (BURNT score<4)(r=0.12, p=0.41). RBP-4 correlated negatively with MELD score (r=-0.57, p=0.001) Conclusions: This pilot study proposed that RBP-4 has a role as a biomarker for endstage liver disease, with an independent, inverse relationship with severity of fibrosis, hepatic decompensation, MELD score, and complications of liver failure. There is a positive correlation with insulin resistance, metabolic syndrome, and Adipokines, but not with hepatic steatometry. A larger prospective clinical trial needs to be conducted to validate the unique role of RBP-4 in fibrosis and decompensated liver disease.