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Irritable bowel syndrome (IBS) is characterized by chronic intermittent abdominal pain and associated diarrhea (IBS-D), constipation (IBS-C), or both. IBS can significantly impact patient function and quality of life. The diagnosis of IBS is based on the presence of characteristic symptoms, the exclusion of concerning features, and selected tests to exclude organic diseases that can mimic IBS. The pathophysiology of IBS remains incompletely understood, and new contributing factors have been identified over the past decade. Altered gut immune activation, intestinal permeability, and the intestinal and colonic microbiome may be important factors. Poorly absorbed carbohydrates have been implicated in triggering IBS symptoms. Increasing evidence supports the benefit of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). Although there are several randomized controlled trials of probiotics in IBS, they are typically poorly designed and have not consistently demonstrated efficacy. Until recently, there were few effective treatments for IBS-D. Data from recent clinical trials support the use of rifaximin, eluxadoline, and peppermint oil. Options for the treatment of IBS-C include lubiprostone and linaclotide.

The US Food and Drug Administration has now approved 10 direct-acting antivirals (DAAs) for the management of hepatitis C virus (HCV). These therapies are combined into 6 regimens that are given for varying durations, with or without ribavirin, depending on the viral genotype, the presence or absence of baseline resistance-associated variants (RAVs), and the patient type. RAVs may be present before exposure to a drug or may become detectable de novo during exposure to a drug. Emerging resistant strains are the most common cause of failure of HCV DAA regimens. Second-generation DAAs provide superior coverage of resistant variants compared with first-generation members of that class. They may also cover a broader range of viral genotypes. Numerous clinical trials have evaluated the safety and efficacy of DAAs in a variety of patient populations, including those with cirrhosis, HIV, and end-stage renal disease. This article evaluates the data from these studies, and discusses recommendations from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) guidance document.

Ulcerative colitis (UC) is a chronic inflammatory condition associated with rectal bleeding and urgency, tenesmus, and diarrhea. Several medical therapies can be used in the treatment of UC. Aminosalicylates are widely used based on their efficacy in the induction and maintenance of remission. Although corticosteroids are effective in patients with more severe disease, systemic use is associated with significant safety concerns. The newer corticosteroid budesonide has lower systemic bioavailability and, consequently, a more favorable safety profile. A budesonide extended-release formulation allows once-daily dosing and delivers the agent locally throughout the colon. Biologic agents used for the treatment of moderate to severe UC include the tumor necrosis factor inhibitors infliximab, adalimumab, and golimumab, and the integrin inhibitor vedolizumab. Rectally administered therapy can also be useful in the treatment of UC. In October 2014, the US Food and Drug Administration approved a budesonide foam formulation for inducing remission in patients with active mild to moderate distal UC extending up to 40 cm from the anal verge. Budesonide foam rapidly distributes to the sigmoid colon and the rectum and avoids some of the drawbacks of suppositories and enemas.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with abdominal pain, diarrhea, constipation, or a mix of symptoms. The pathophysiology of IBS is not completely understood but appears to involve genetics, the gut microbiome, immune activation, altered intestinal permeability, and brain-gut interactions. There is no gold standard for diagnosis. Several sets of symptom-based guidelines exist. Treatment strategies for IBS may include both nonpharmacologic and pharmacologic approaches. Lifestyle modifications that aim to improve exercise, sleep, diet, and stress may be warranted. Recent data suggest that a gluten-free diet and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) may benefit some patients. For patients with diarrhea-predominant IBS, treatment options include the synthetic peripheral μ-opioid receptor agonist loperamide, antispasmodic agents, antidepressants, serotonin 5-HT3 antagonists, and the gut-specific antibiotic rifaximin. Ongoing research is evaluating the use of probiotics. For patients with constipation-predominant IBS, therapeutic strategies may include dietary fiber, laxatives, and the prosecretory agents lubiprostone and linaclotide. Research is continuing to optimize the use of available agents and evaluating new approaches to further improve the care of patients with IBS.

Helicobacter pylori (H pylori) is a common chronic bacterial infection that is an important cause of peptic ulcer disease and gastroduodenal disease in children. H pylori is also associated with extragastric manifestations, including growth reduction, iron-deficiency anemia, and idiopathic thrombocytopenic purpura. Current guidelines recommend endoscopy with biopsy for the definitive demonstration of H pylori infection. In contrast to serology, the fecal antigen test and the urea breath test provide reliable, sensitive, and specific results for detecting active H pylori infection in children before and after treatment. The first-line treatment option for pediatric patients is triple therapy with a proton pump inhibitor and 2 antibiotics, which include amoxicillin and clarithromycin or metronidazole. Decreasing eradication rates and the emergence of antibiotic-resistant strains of H pylori have led to the use of other treatments, such as sequential therapy or triple therapy with newer antibiotics, particularly in geographic areas with high rates of antibiotic resistance. Patients should be tested after treatment to confirm eradication, as the absence of symptoms does not necessarily mean that H pylori is no longer present. This clinical roundtable monograph provides an overview of H pylori infection, as well as expert insight into the diagnosis and management of H pylori infection in children.

Helicobacter pylori (H pylori) infection is one of the most common chronic bacterial infections worldwide. International guidelines recommend H pylori eradication in several scenarios: patients with peptic ulcer disease, patients who have had endoscopic resection of early gastric cancer, and patients with a gastric mucosa-associated lymphoid tissue lymphoma (MALToma). There is variability among the guidelines for other conditions. Treatment options for H pylori infection include triple, quadruple, and sequential therapy. Ideally, patients in whom previous eradication attempts failed and those suspected to have resistant strains should be considered for antimicrobial sensitivity testing, which requires culture of gastric mucosal biopsies; such testing, however, has limited availability in the United States. Resistance rates vary by location depending on local antibiotic usage rates. As such, the success rates associated with different regimens vary throughout the world. Many patients with H pylori infection are asymptomatic, whereas others are diagnosed with the infection during evaluation of dyspeptic symptoms or following a diagnosis of peptic ulcer. Symptoms may not be an accurate indicator of treatment success. The American College of Gastroenterology (ACG) endorses the carbon 13-labeled urea breath test ((13)C-UBT) as the most reliable test to confirm H pylori eradication. This clinical roundtable monograph begins with an overview of H pylori infection and then discusses treatment, antibiotic resistance, management of patients with antibiotic resistance, and posttreatment testing, with a focus on the ACG guidelines.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, with an increasing incidence projected through 2020. HCC is the third-leading cause of cancer-related deaths worldwide. Management of HCC is complicated by the fact that these patients also have a cirrhotic or otherwise diseased liver that led to the tumorigenesis. To aid in treatment decisions, several staging systems have been developed. In the United States, the Barcelona Clinic Liver Cancer (BCLC) system has emerged as the predominant system, owing to its concomitant consideration of tumor stage, liver function, and physical status, as well as its ability to identify patients with early-stage disease who may benefit from curative therapies. Surveillance for HCC has gained increasing importance in light of several studies demonstrating both clinical and cost benefits. Once HCC is detected and diagnosed, it is usually managed according to its BCLC stage. Patients with early-stage disease often benefit from potentially curative therapies, such as surgical resection and liver transplantation. Often, local ablation such as radiofrequency ablation or percutaneous alcohol injection can be used not only as an effective treatment, but also as a bridge therapy to maintain the status of patients on the liver transplant list. Intermediate-stage patients are typically treated with transarterial chemoembolization, but have a high rate of disease recurrence. The multikinase inhibitor sorafenib is the only treatment option approved for patients with advanced-stage HCC. Sorafenib has demonstrated a significant survival advantage in these patients. Numerous studies have evaluated other novel targeted therapies in this setting, but none have shown superiority to sorafenib.

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder and affects up to 12% to 15% of adults in the United States, with a higher prevalence among women and those younger than 50 years. IBS adversely impacts quality of life and medical expenditures, with significant costs arising from healthcare visits and reduced workplace productivity. Recent studies have shown that the adverse effects of IBS are so significant that many patients are willing to accept risks of adverse events from effective treatment to gain symptom relief. Alosetron is a 5-HT3 receptor antagonist approved by the US Food and Drug Administration (FDA) for women with severe diarrhea-predominant IBS that has not responded to traditional therapies. Alosetron yields overall improvements in IBS symptoms in 51% of patients vs 36% treated with placebo, with efficacy continuing undiminished over the course of a 48-week randomized, controlled trial. In real-world clinical practice, patients receiving alosetron had significant improvements in multiple IBS-related clinical parameters, including the new FDA IBS-diarrhea composite endpoint, lower gastrointestinal symptoms, fecal incontinence, and quality of life. Ischemic colitis and complications of constipation have been rare in occurrence. After nearly a decade of alosetron use under the risk management plan, adjudication of ischemic colitis and complications of constipation cases indicate that their incidence rates have remained low and stable.

For treatment of moderate-to-severe active Crohn's disease, clinicians generally rely on immunosuppressants (including azathioprine and 6-mercaptopurine), corticosteroids, and antibodies against tumor necrosis factor α. However, a significant proportion of patients do not respond to these therapies, lose response over time, or are intolerant to these therapies. In such cases, one of the only remaining pharmacologic treatment options is natalizumab, an α4 integrin-targeted antibody. Unfortunately, 3 cases of progressive multifocal leukoencephalopathy (PML) were reported in natalizumab-treated patients in 2005, shortly after natalizumab's approval by the US Food and Drug Administration (FDA). Natalizumab was subsequently withdrawn from the market but was then reintroduced in 2006 under close supervision by the FDA. Careful review of postmarketing data revealed 3 major risk factors for the development of natalizumab-associated PML, the most significant of which is prior exposure to the JC virus (JCV). To help identify patients who may be at higher risk for developing natalizumab-associated PML, a JCV antibody assay was developed that can detect anti-JCV antibodies in patients' blood. Clinicians can now consider a patient's anti-JCV antibody status together with the other major risk factors for natalizumab-associated PML-duration of natalizumab therapy and prior immunosuppressant use-to more accurately gauge the risks and benefits of natalizumab therapy in a particular patient.

Boceprevir or telaprevir plus ribavirin (RBV) and pegylated interferon-α (pegIFN-α) is the new standard-of-care therapy for patients who are chronically infected with genotype 1 hepatitis C virus (HCV). The addition of these protease inhibitors to the RBV/pegIFN-α combination regimen has significantly improved rates of sustained virologic response (SVR); however, the incidence of anemia has also increased significantly. Anemia can interfere with patients' quality of life, work productivity, and treatment adherence. Severe anemia can cause morbidity and even mortality. For the management of anemia during triple combination therapy, RBV dose reduction is recommended as an initial course of action. Retrospective analyses of carefully selected patient cohorts suggest that RBV dose reduction does not reduce SVR rates. However, this observation needs to be confirmed in prospective trials with cohorts that more accurately reflect the challenging patients treated in real-world practice. Adequate doses of RBV should be maintained during triple combination therapy, as phase II trials have demonstrated that RBV is essential for attaining optimal SVR rates and preventing viral breakthrough, relapse, and emergence of resistant variants. This roundtable addresses key points related to the management of anemia in the era of triple combination therapy, including the increasing problem of anemia, strategies for anemia management, and the importance of maintaining adequate RBV exposure as part of the HCV treatment regimen.

Diagnosis of inflammatory bowel disease (IBD) is complicated and is based on a combination of patient history and physical examination in association with laboratory, endoscopic, histologic, and radiographic investigations. Determination of the correct diagnosis is important for its implications in selecting treatment and in the timing and type of surgery that may be required. Information from testing incorporating serologic, genetic, and inflammatory markers can help to clarify the clinical picture. Measurement of biomarkers not only helps to differentiate a diagnosis of IBD versus non-IBD, it can also help to distinguish between ulcerative colitis and Crohn's disease in difficult cases. In this monograph, 5 cases illustrate how specialized testing can provide important information that can aid in diagnosis.

Special Reporting on: Novel Infliximab and Antibody-to-lnfliximab Assays Are Predictive of Disease Activity in Patients with Crohn’s DiseaseAntibodies to Infliximab Can Either Be Persistent or Transient: A Retrospective Case-Control Study in IBD Patients Treated with Infliximab Maintenance TherapyPutting It Together: Drug Levels and Disease Activity to Tailor TherapyInfliximab Concentration and Clinical Outcome in Patients with Ulcerative Colitis

A number of agents can reduce viral replication in patients with chronic hepatitis B, but most patients do not undergo a curative response to these drugs and therefore require long-term therapy. Thus, recent studies have investigated the long-term safety, efficacy, and resistance profiles of several antiviral nucleotide/nucleoside agents: lamivudine, telbivudine, adefovir dipivoxil, entecavir, and tenofovir. The most recent data have revealed that lamivudine and telbivudine produce high rates of resistance when treatment is continued for 2–5 years; as a result, these agents are no longer preferred for first-line monotherapy. Entecavir and tenofovir, on the other hand, appear to have favorable safety and efficacy profiles when used as monotherapy, with very low rates of resistance over 5 years. In order to help clinicians incorporate these data into clinical practice, this monograph will review recently published data on hepatitis B antiviral medications, as well as explore when to consider cessation of therapy. The treatment of special patient populations and the need to screen patients for hepatocellular carcinoma will also be discussed.

A burden on both patients and the healthcare system, irritable bowel syndrome (IBS) is a prevalent condition that can result in high medical costs, frequent visits to the doctor, missed work, and anxiety and depression in the patient. This chronic disorder causes abdominal pain or discomfort and is characterized by abnormal defecation that presents mainly as either constipation or diarrhea symptoms. IBS associated with diarrhea (IBS-D) accounts for approximately one third of all IBS patients. IBS-D treatment can be confusing and frustrating for both the patient and the physician, complicated by the fact that a specific therapeutic algorithm has not been developed. Treatment options are widely varied, consisting of both nonpharmacologic (dietary changes) and pharmacologic (loperamide and alosetron) interventions. Furthermore, mounting evidence suggests a possible role for small intestinal bacterial overgrowth in the pathogenesis of IBS-D; thus, both antibiotics (such as rifaximin) and probiotics are frequently used to treat patients. Although all of these interventions elicit some measure of symptom response in a proportion of treated patients, there is no standard of care for the treatment of IBS-D. Thus, physicians would benefit from knowledge of all of the strategies used to treat IBS-D, in order to treat patients appropriately.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related morbidity and mortality worldwide. In the United States, HCC is the main cause of death in patients with cirrhosis, and the incidence of this malignancy is on the rise. Because HCC is associated with a particularly poor prognosis, emphasis is placed on surveillance of high-risk patients. Early detection allows a greater chance of diagnosing HCC before it has spread, thus increasing the chances that the patient can be potentially cured with surgical techniques such as resection and transplantation. However, most cases of HCC are not diagnosed until at least some of the cancer has spread or multiple nodules exist. For these patients, treatment options include percutaneous and transarterial ablation, as well as systemic chemotherapy. Systemic therapy is now considered the standard of care for patients with advanced tumors. Traditional treatment was based on cytotoxic chemotherapeutic agents, such as doxorubicin. This approach was associated with minimal benefit and a high rate of toxicity. Recently, targeted agents have proven more effective and safer in this setting. The oral multikinase inhibitor sorafenib is now approved for the treatment of unresectable HCC and is currently the only approved agent for advanced HCC. In order to maximize the benefit of sorafenib and other investigational agents for patients with advanced disease, effective interventions have been designed to mitigate their associated adverse events, such as hand-foot skin reactions and hypertension.

Gastroparesis, or chronic delayed gastric emptying without mechanical obstruction, affects about 40% of patients with type 1 diabetes and up to 30% of patients with type 2 diabetes. Diabetic gastroparesis (DGP) typically causes nausea, vomiting, early satiety, bloating, and postprandial fullness. These symptoms can be extremely troubling and result in poor quality of life. The diagnosis of DGP is made by documenting the presence of chronic upper gastrointestinal (GI) symptoms, ruling out mechanical obstruction, and demonstrating delayed gastric emptying. The usual treatment for DGP includes dietary modifications, prokinetic agents, and antiemetic agents. Although the majority of patients have mild-to-moderate disease that can be managed using these measures, a substantial percentage of patients have severe DGP that is characterized by inadequate oral intake, malnutrition, weight loss, and frequent hospitalizations. Optimal management of these patients presents a difficult challenge for the clinician, although emerging treatment options, such as gastric neurostimulation, are encouraging. Patients with DGP often present with gastric comorbidities, including gastroesophageal reflux disease, intestinal dysmotility, and fungal and bacterial infections of the GI tract. This monograph will present an overview of the pathophysiology of DGP, review diagnostic testing with a discussion of emerging technology, and present the latest research in treatment options for DGP. In addition, management strategies for refractory DGP and gastric comorbidities will be described.

The relationship between gastroparesis and GERD is multi-factorial. The delay in gastric emptying associated with gastroparesis can lead to prolonged gastric retention of food that may have a propensity to reflux. Because gastroparesis allows material to remain in the stomach, there is an increase in the gastroesophageal pressure gradient, gastric volume, and the volume of potential refluxate. Additionally, the prolonged exposure of material in the stomach can increase gastric acid secretion. The onset of gastroparesis has been attributed to several causes, including comorbidities (mainly diabetes), surgical complications, and the use of specific medications (including anticholinergics, narcotics, tricyclic antidepressants, and calcium channel blockers). The etiology of some cases of gastroparesis remain unclear, a condition termed idiopathic gastroparesis. Symptoms commonly associated with gastroparesis or GERD, including nausea, vomiting, and regurgitation, may delay drug absorption. This has the potential to greatly impact systemic absorption and concentration of drugs. Several patient populations may benefit from the use of medication formulations that offer an alternative to swallowing a traditional tablet. In addition, prokinetic drugs, such as metoclopramide, are used in the first-line treatment of gastroparesis to improve the contractility of the gut muscles, as well as the movement of contents through the gastrointestinal system and regulate drug metabolism and absorption.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer worldwide. The impact of this disease is great, as it is the third-leading cause of global cancer-related mortality. Traditionally, patients with HCC did not present until they were in late stages of the disease, limiting their therapeutic options. In recent years, improvements in disease awareness, as well as in surveillance and screening techniques, have led to earlier diagnosis and the potential for improved prognosis and patient survival. Some current treatments rely on surgical or locoregional techniques, many of which were not suitable for patients with advanced stage disease. In addition to surgical resection, advances in radiofrequency ablation and tran-sarterial chemoembolization procedures have increased survival. However, these improvements are short-lived, requiring alternative therapies for patients with recurrent or advanced-stage HCC. Although conventional chemotherapeutic agents have traditionally been administered in this setting, their role in HCC is decreasing as advances in targeted therapies have proven successful in this disease. Notably, treatment with the multi-targeted tyrosine kinase inhibitor sorafenib led to significant improvements in survival in phase III clinical studies, resulting in its approval for unresectable HCC. This clinical roundtable provides an overview of HCC, first focusing on the recognition of the disease. This overview is followed by an in-depth discussion of successful management of HCC using a multimodality approach. Techniques in surgical resection and locoregional therapy are described, as are the safety and efficacy of new systemic and targeted agents. Upon completion of this activity, physicians will have an improved understanding of the occurrence, diagnosis, and treatment of HCC.