Antibiotics for the Treatment of Irritable Bowel Syndrome

Abstract: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with an estimated worldwide prevalence of 10–20%. IBS can be associated with severe gastrointestinal symptoms, including abdominal pain, bloating, and altered bowel function. Although the causes of IBS remain undefined, recent research has increasingly suggested roles for gut flora in IBS. These roles involve postinfectious IBS, which can occur after a single episode of acute gastroenteritis, and small intestinal bacterial overgrowth, in which elevated populations of aerobic and anaerobic bacteria cause abdominal pain and altered bowel function. More recently, potential roles for methanogens in contributing to IBS subtypes have also been identified. In this paper, we review the different mechanisms by which gut flora may contribute to IBS and also discuss the efficacy and safety of various antibiotic therapies for treating IBS symptoms.

IL-28B As a Predictor of Sustained Virologic Response in Patients with Chronic Hepatitis C Virus Infection

Abstract: Genome-wide association studies have recently identified single nucleotide polymorphisms in proximity to the interleukin-28B (IL-28B) gene that can predict sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection who are undergoing therapy with pegylated interferon (IFN) α and ribavirin. IL-28B encodes IFN-λ3, a type III IFN involved in host antiviral immunity. Favorable variants of the 2 most widely studied IL-28B polymorphisms, rs12979860 and rs8099917, are strong pretreatment predictors of early viral clearance and SVR in patients with genotype 1 HCV infection. Variations in the distribution of IL-28B alleles may partly explain differences in SVR rates among ethnic groups. Further investigations have implicated IL-28B in the development of chronic HCV infection versus spontaneous resolution of acute infection and suggest that IL-28B may be a key factor involved in host immunity against HCV. Clinical trials of IFN-λ as a therapeutic agent for chronic HCV infection are currently underway. The use of IL-28B polymorphisms as a predictive tool will have a major impact on treatment strategies for chronic HCV infection, particularly in the context of emerging therapies and direct-acting antiviral agents.

Targeting Mucosal Healing in Crohn’s Disease

Abstract: The goal of medical treatment for Crohn’s disease includes improving patients’ quality of life while reducing the need for hospitalization and surgery. The current medical armamentarium includes 5-aminosalicylates, corticosteroids, immunomodulators, and biologic agents. In the past, response to treatment was measured by clinical improvement in symptoms; however, with the advent of disease-modifying medications, mucosal healing has emerged as an increasingly important goal of therapy. Mucosal healing, or endoscopic remission, is associated with increased rates of clinical remission, fewer hospitalizations, and fewer abdominal surgeries. Both the immunomodulator and biologic classes of medications are effective at inducing mucosal healing. Despite several limitations, mucosal healing has become a desirable and valid measure of disease activity.

Ethnic Disparities in Liver Transplantation

Abstract: End-stage liver disease is a major cause of morbidity and mortality among ethnic minorities. In the United States, ethnic minorities comprise approximately 30% of all adult liver transplantations performed annually. Several studies have suggested that ethnic populations differ with respect to access and outcomes in the pre- and post-transplantation setting. This paper will review the existing literature on ethnic variations in the adult liver transplantation population.

Searching for the Delta: 5-Aminosalicylic Acid Therapy for Crohn’s Disease

Abstract: Crohn’s disease (CD) is a chronic inflammatory condition that often requires lifelong medical therapy for the induction and maintenance of remission. Oral mesalamine (5-aminosalicylic acid [5-ASA]) therapy has several forms, which can be categorized into oral formulations and prodrugs. The ability to demonstrate the efficacy of 5-ASA is limited in most clinical trials by the nonspecific endpoints of the Crohn’s Disease Activity Index. Overall, clinical trials have not shown 5-ASA therapy to be superior to placebo for the induction of remission, with the exception of sulfasalazine in colonic CD. 5-ASA therapy has also not been shown to be superior to placebo for maintenance of medically induced remission; however, mesalamine may have a modest effect in surgically induced remission. Further research is needed regarding the optimal monitoring and therapy for patients with mild CD who often achieve remission with placebo in clinical trials.

Current Concepts in the Pathophysiology and Management of Hepatic Encephalopathy

Abstract: Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or portosystemic shunting of blood flow. The pathophysiology of this disease is quite complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Recent hypotheses implicate low-grade cerebral edema as a final common pathway for the pathophysiology of HE. Management of this condition is multifaceted and requires several steps: elimination of precipitating factors; removal of toxins, both by reducing them at their source and by augmenting scavenging pathways; modulation of resident fecal flora; proper nutritional support; and downregulation of systemic and gut-derived inflammation.

Extraintestinal Manifestations of Inflammatory Bowel Disease

Abstract: xtraintestinal manifestations of inflammatory bowel disease are prevalent in both ulcerative colitis and Crohn’s disease. The most common manifestations involve the musculoskeletal and dermatologic systems. Other manifestations involve the hepatopancreatobiliary system (eg, primary sclerosing cholangitis) as well as the ocular, renal, and pulmonary systems. A multidisciplinary team approach is often needed for effective management, and emergency situations require prompt evaluation.

Direct-Acting Antiviral Medications for Chronic Hepatitis C Virus Infection

Abstract: Treatment of hepatitis C virus has traditionally been difficult because of low rates of treatment success and high rates of treatment discontinuation due to side effects. Current standard therapy consists of pegylated interferon α and ribavirin, both of which have nonspecific and largely unknown mechanisms of action. New therapies are in development that act directly on the hepatitis C virus at various points in the viral life cycle. Published clinical trial data on these therapies are summarized in this paper. A new era of hepatitis C virus treatment is beginning, the ultimate goals of which will be directly targeting the virus, shortening the length of therapy, improving sustained virologic response rates, and minimizing side effects.

Crohn’s Disease: The First Visit

Abstract: A Crohn’s disease patient’s first visit to a new practice is the optimal time to collect important clinical data and identify appropriate therapies. A methodologic approach to this visit is crucial. The focus of this visit should be on preparing the patient for the initiation of treatment, with particular attention to the necessary steps prior to the use of immunosuppressive and biologic agents. This paper is intended to provide recommendations and a checklist for the initial assessment and evaluation of patients with Crohn’s disease.

Keys to Success with Clinical Trials

Seymour Katz, MD, FACP, MACG Heather Dufficy, BA, NREMT-P Christy John, MSHS Dr. Katz is Clinical Professor of Medicine at Albert Einstein College of Medicine in Bronx, […]

New Developments in Traveler’s Diarrhea

Abstract: Traveler’s diarrhea (TD) is a crucial area for research, as it affects millions of tourists each year and creates a large economic burden. More than 60% of TD cases are caused by a variety of bacterial enteropathogens: diarrhea-producing Escherichia coli, Shigella, Campylobacter, Salmonella, Aeromonas, Plesiomonas, and noncholera Vibrios. Noroviruses are also an important cause of morbidity among travelers. Recent studies have identified host genetic risk factors associated with susceptibility to pathogen-specific TD. Prevention strategies should be emphasized, as all individuals with TD experience approximately 24 hours of disability and 5–10% experience chronic functional bowel disease. Poorly absorbed rifaximin provides protection for trips lasting 2 weeks or less. TD vaccines are also currently in development. All individuals planning trips to developing regions should be armed with 1 of the 3 agents that have shown efficacy for self-treatment of TD: ciprofloxacin (or levofloxacin), rifaximin, or azithromycin, depending upon the location of the trip. Although global epidemiologic changes in etiologic agents as well as antibiotic resistance patterns have been better understood recently, changes should be expected during the next decade due to new prevention and treatment approaches.

Transitional Care in Inflammatory Bowel Disease

Abstract: Transitional care is an organized effort to provide pediatric patients with the tools and resources they need to assume personal responsibility for their medical care while facilitating their transfer from a pediatrician to an adult practitioner. Since inflammatory bowel disease (IBD) is usually chronic and up to 25% of IBD patients are diagnosed before the age of 18 years, transitional care is an important consideration for adolescent and young adult patients. The importance of transitional care for chronic diseases that begin in childhood has been recognized in a number of published recommendations. However, most of these recommendations arise from intuitive reasoning, as physicians lack information regarding the need for transitional care, optimal delivery protocols, and the efficacy of transition programs. Even fewer studies have been published regarding transitional care in IBD. Current guidelines stress the importance of providing patients with educational resources to help them develop the skills they need to manage their care as independent adults, introducing the concept of transfer to adult care in advance of the actual transfer, and developing routes of communication to facilitate the transfer from pediatric to adult care providers. Future studies should aim to elucidate which programs are effective and how they should be implemented.

Updates in the Management of Hepatocellular Carcinoma

Abstract: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, and its increasing incidence worldwide is a cause for concern. Fortunately, advances in diagnostic and therapeutic approaches have contributed to earlier detection and treatment. As cancer epidemiology studies continue to elucidate the natural history of liver diseases, greater understanding of HCC has led to improved risk stratification and earlier enrollment of high-risk patients in cancer screening and surveillance programs. Improved survival rates among HCC patients also reflect significant advances in available treatment options. Advances in surgical techniques are pushing the boundaries of resection for localized disease, and progress in the field of transplantation has led to refinements in listing criteria and improved post-transplantation outcomes. The evolving field of locoregional therapies—including percutaneous ablation and transarterial chemoembolization—continues to provide novel therapeutic options that can be used in place of, or in addition to, surgical approaches. Recent advances in systemic multikinase inhibitor therapies have also demonstrated significant benefits for advanced-stage disease, and these therapies also show promise as adjuvant treatments for earlier-stage disease. This article provides an update on the management of HCC, with a focus on revised guidelines for screening and an in-depth discussion of emerging novel therapies.