Nithya Krishnaswamy

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.

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.

Effects of triple-drug therapy with nitazoxanide, high-dose ribavirin and peginterferon-α-2a in patients with chronic hepatitis C

The historical standard of care for patients with chronic hepatitis C virus (HCV) was peginterferon (PEG IFN) and ribavirin combination therapy, yielding sustained virological response (SVR) rates of 38–52% in HCV genotype 1 patients. This study evaluated a novel three‐drug regimen of nitazoxanide and high‐dose ribavirin as lead‐in therapy, followed by PEG IFN‐α‐2a in triple therapy.

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.

Effect of melatonin in functional heart burn – a randomized placebo-controlled clinical trial

Background: Melatonin is a safe and effective treatment for patients with functional pain and gastrointestinal disorders. Objective: To evaluate the efficacy and safety of melatonin for 3 months in patients with functional heartburn. Methods: In the randomized, placebo-controlled pilot study, patients with functional heartburn were treated with omeprazole 20 mg before breakfast and randomized to receive either melatonin 6 mg (n = 20), nortripty line 25 mg (n = 20), or placebo (n = 20) at bedtime for 3 months. Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQOL) scores were assessed at baseline and at the end of the study. Results: Melatonin improved GERD-HRQOL scores compared with nortriptyline (P = 0.0015) and placebo (P < 0.0001). Fewer adverse events were reported by patients receiving melatonin compared with those receiving nortriptyline or placebo. Conclusions: Melatonin was a safe and effective treatment for functional heartburn.

M1270 Transdermal Rivastigmine for Treatment of Encephalopathy in Liver Cirrhosis, a Randomized Placebo Controlled Trial (T R E C Trial)

G A A b st ra ct s SIBO vs 2 of the 48 healthy controls (4%) (p<0.0001). SIBO prevalence correlated with the severity of LC (68.2% of Child C patients vs. 56.2% of Child B and 31.2% of Child A patients), with the presence of ascites (66% in ascitic patients vs. 27% in non-ascitic patients), and with a history of SBP (92% of patients with SBP vs. 48% of those without SBP). A significant correlation was found between presence of SIBO and altered IP in patients with most severe degree of LC (Child A pts: R=0.07, NS; Child B pts: R=0.35, p=0.005; Child C pts: R=0.29, p=0.03). CONCLUSIONS: SIBO seems to have an higher prevalence in LC, and correlates with LC severity and altered IP. This association suggests that SIBO may affect intestinal permeability of splancnic vessels and/or peritoneal membranes leading to SBP outbreak in LC. Future interventional studies are needed to confirm these preliminary data.