Effect of Vitamin E and Alpha Lipoic Acid in Nonalcoholic Fatty Liver Disease: A Randomized, Placebo-Controlled, Open-Label, Prospective Clinical Trial (VAIN Trial)

Objective: Antioxidants, including alpha lipoic acid (ALA) and vitamin E, are efficacious for the treatment of nonalcoholic fatty liver disease (NAFLD). The objective was to evaluate the effects of ALA and vitamin E alone or combined as therapy for patients with NAFLD and nonalcoholic steatohepatitis (NASH). Design: Placebo-controlled, open-label, prospective study in which patients with NAFLD and NASH were randomized to treatment with ALA 300 mg (n = 40), vitamin E 700 IU (n = 40), ALA 300 mg plus vitamin E 700 IU (n = 40), or placebo (n = 35) daily for 6 months. Body mass index, homeostasis model assessment scores, fibrosis and steatosis markers, and diagnostic laboratory tests were assessed at baseline and at the end of the study. Results: Treatment with ALA and vitamin E alone or in combination, improved inflammatory cytokine levels, steatosis scores, homeostasis model assessment scores, and triglyceride levels after 6 months relative to baseline. Conclusion: Alpha lipoic acid and vitamin E, either alone or in combination, were effective treatments for patients with NAFLD and NASH.

The effect of melatonin in functional heartburn: 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.

Randomized, Placebo-Controlled Trial of Transdermal Rivastigmine for the Treatment of Encephalopathy in Liver Cirrhosis (TREC Trial)

Objectives: Cognitive dysfunction in patients with hepatic encephalopathy (HE) may be caused by alterations in cholinergic neurotransmission. The objective of the study was to evaluate the efficacy and safety of transdermal rivastigmine in improving cognitive function in patients with overt HE. Design: Randomized, controlled pilot study in which patients with grade 2 or 3 HE were treated with lactulose and randomized to receive either transdermal rivastigmine or placebo for 21 days. The modified encephalopathy scale (MES), object recognition test (ORT), trail test (TT), and serum ammonia were assessed at baseline weekly. Electroencephalography was performed at baseline and the final week of the study. Results: Patients were treated with lactulose (20 g/30 mL three times per day) and either transdermal rivastigmine (4.6 mg/d;n = 15) or placebo (n = 15). Transdermal rivastigmine significantly improved MES, ORT, and TT results compared with placebo (P ≤ 0.0001 at all 3 weeks for all 3 assessments). Serum ammonia improved in both treatment groups, although there was significantly greater improvement with placebo than rivastigmine after 2 weeks of treatment (P What is already known about this subject? ? Current approaches to the management of HE are primarily designed to reduce the levels of ammonia and other gut-derived toxins. ? Traditional strategies for HE treatment have included non-absorbable disaccharides (to decrease bowel transit time) or rifamixin (non-absorbable antibiotics to reduce ammoniogenic flora). ? No transdermal cholinomimetic agents have been used with oral lactulose to date, in HE. What are the new findings? ? Transdermal rivastigmine is safe for use in patients with grade 2 & 3 HE. ? Transdermal rivastigmine in combination with oral lactulose in this study is far superior to lactulose alone in improving cognitive function. How might it impact on clinical practice in the foreseeable future? ? Transdermal rivastigmine in combination with oral lactulose can be used safely in clinical practice. ? Transdermal rivastigmine in combination with oral lactulose is efficacious in improving cognitive function in moderate HE (grade 2/3). Further validation through large randomized clinical trials is required before this is adopted in universal clinical practice of treating HE.

Effects of Metoclopramide Orally Disintegrating Tablet in Optimizing Late Outpatient Endoscopy: A Randomized Double-Blind Placebo-Controlled Clinical Trial

Aims: Metoclopramide has been used as a gastro-kinetic agent but the safety and effects of different preparations of metoclopramide on preparation for outpatient endoscopy are largely unknown. The study aimed to evaluate the (1) Safety of using ODT (orally disintegrating tablet) or TT (traditional tablet) metoclopramide pre-endoscopy in non-fasting patients compared with placebo (2) Impact of ODT or TT metoclopramide on sedation and recovery times compared with placebo. Methods: A double blind randomized placebo-controlled trial with 3 arms;Metoclopramide ODT (n = 43), Metoclopramide TT (n = 43) and Placebo (n = 43). Results: Metoclopramide ODT had fewer adverse events compared with TT or placebo. Recovery time was significantly shorter with use of either metoclopramide versus placebo (P < 0.001) & total sedation time was also significantly shorter in the metoclopramide groups versus placebo (P < 0.001). Conclusion: Metoclopramide ODT is safe and beneficial in endoscopic procedures requiring limited access to food and liquid.

A Study on the Safety of Liver Biopsy Inpatients with Von Willebrand’s Disease

Objectives: Liver biopsy remains the gold standard for diagnosis of chronic liver diseases. Outpatient percutaneous biopsy is generally safe with a mortality rate of 0.17% and hospitalization rate for bleeding of 3%. Von Willebrand disease (vWD) syndrome is the most common inherited hematological disorder with a prevalence of 1% - 3% globally. We sought to study whether vWD increases the risk of bleeding for liver biopsies. Methods: All patients (n = 120) who underwent outpatient percutaneous liver biopsies from 1997 to 2007 were analyzed. Demographics, PT/INR, platelet count, vW antigen and ristocetin induced platelet aggregation were studied. Results: No vWD patients had major bleeding that required transfusion, hospitalization or surgery but 9 (75%) had minor local bleeding and all had ecchymosis, which resolved spontaneously within 24 hours. Conclusions: Patients with vW factor deficiency can undergo percutaneous liver biopsy without major bleeding. Minor bleeding may occur at a slightly higher rate. vWD is not a contraindication to percutaneous liver biopsy.