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

AIM: 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. METHODS: A prospective, open-label pilot study was conducted in treatment-naive patients with HCV genotype 1. Patients received nitazoxanide 500 mg twice a day for 2 weeks, then nitazoxanide plus ribavirin 1400 mg/day for 2 weeks, then nitazoxanide plus ribavirin plus PEG IFN-α-2a 180 µg weekly for 12 weeks, followed by ribavirin plus PEG IFN-α-2a for 12 weeks (48 weeks if HCV RNA negative after week 24). Primary outcome was SVR. Other outcomes included very rapid virological response (VRVR), rapid virological response (RVR), early virological response (EVR), end-of-treatment response (ETR), and safety and tolerability. RESULTS: Thirty-three patients with a mean age of 46 years, detectable HCV RNA (64% with <600 000 IU/mL), and METAVIR fibrosis scores (F1:F2:F3) of 15%:49%:36% were enrolled. Outcomes were as follows: SVR, 67% (22/33); VRVR, 39% (13/33); RVR, 48% (16/33); EVR, 70% (23/33); and ETR, 67% (22/33). Most patients required at least one growth factor. Two patients discontinued because of adverse events. CONCLUSION: This three-drug regimen was effective in achieving SVR in patients with HCV genotype 1. No patients relapsed, and the toxicity profile was favorable. Further studies on the role of nitazoxanide in the treatment of chronic HCV are warranted.

Novel endoscopic delivery modality of infrared coagulation therapy for internal hemorrhoids.

BACKGROUND: A novel endoscopic delivery system for infrared coagulation therapy (IRC) has been designed recently. IRC is a well-established treatment for symptomatic internal hemorrhoids. Patients frequently undergo lower endoscopy before hemorrhoid treatment to eliminate other sources of bleeding. Current treatment options are difficult to perform without an anal retractor, adequate lighting, and specialized instruments. Endoscopic IRC is an attractive alternative to standard IRC, because it can be performed during the lower endoscopy. TECHNIQUE: Endoscopic IRC utilizes infrared radiation generated by a control box, which is applied to the tissue through a flexible, fiber optic light guide (Precision Endoscopic Infrared Coagulator™). The light guide is placed through the colonoscope or flexible sigmoidoscope in the same chamber as other endoscopic instruments. METHODS: A retrospective review was performed using a prospectively collected database. A standardized protocol was utilized in all patients. Patients graded their symptoms before and after therapy by using the visual analog symptom severity scoring system (range, 0-10). These results were analyzed by using the nonparametric Wilcoxon signed-rank test. Exact P values were computed by using the R function wilcox.exact. RESULTS: A total of 55 patients underwent endoscopic IRC for predominately grade II and grade III symptomatic internal hemorrhoids (71 %). There were 22 (40 %) female patients. Posttherapy results indicated a significant improvement in global symptoms (pretreatment average global score = 2.24 vs. posttreatment average global score = 0.28; P < 0.0001). There have been no adverse events reported to date. CONCLUSIONS: Endoscopic IRC provides improved visibility and efficiency, allowing simultaneous treatment of symptomatic internal hemorrhoids at the time of lower endoscopy. Patients experienced significant improvement in their symptoms after a single session of endoscopic IRC. There are a variety of additional endoscopic IRC therapeutic utilities: endoscopic management of angiodysplasia, inflammation, hemostasis, and NOTES applications.

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.

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.

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.