The aspartate aminotransferase-to-platelet ratio index (APRI), a tool with limited expense and widespread availability, is a promising noninvasive alternative to liver biopsy for detecting hepatic fibrosis. The objective of this study was to systematically review the performance of the APRI in predicting significant fibrosis and cirrhosis in hepatitis B-related fibrosis.

As obesity reaches epidemic proportions, nonalcoholic fatty liver disease (NAFLD) is becoming a frequent cause of patient referral to gastroenterologists. There is a close link between dysfunctional adipose tissue in NAFLD and common conditions such as metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. This review focuses on the pathophysiology of interactions between adipose tissue and target organs in obesity and the resulting clinical implications for the management of nonalcoholic steatohepatitis. The release of fatty acids from dysfunctional and insulin-resistant adipocytes results in lipotoxicity, caused by the accumulation of triglyceride-derived toxic metabolites in ectopic tissues (liver, muscle, pancreatic beta cells) and subsequent activation of inflammatory pathways, cellular dysfunction, and lipoapoptosis. The cross talk between dysfunctional adipocytes and the liver involves multiple cell populations, including macrophages and other immune cells, that in concert promote the development of lipotoxic liver disease, a term that more accurately describes the pathophysiology of nonalcoholic steatohepatitis. At the clinical level, adipose tissue insulin resistance contributes to type 2 diabetes mellitus and cardiovascular disease. Treatments that rescue the liver from lipotoxicity by restoring adipose tissue insulin sensitivity (eg, significant weight loss, exercise, thiazolidinediones) or preventing activation of inflammatory pathways and oxidative stress (ie, vitamin E, thiazolidinediones) hold promise in the treatment of NAFLD, although their long-term safety and efficacy remain to be established. Better understanding of pathways that link dysregulated adipose tissue, metabolic dysfunction, and liver lipotoxicity will result in improvements in the clinical management of these challenging patients.

There have been inconsistent results published about the relationship between excess body weight, expressed as increased body mass index (BMI), and risk of colorectal adenoma (CRA). We conducted a meta-analysis to explore this relationship. We focused on whether the relationship varied based on the sex of the study subjects, study design, features of the polyps, or potential confounders, including alcohol use, nonsteroidal anti-inflammatory drug use, smoking, and exercise.

Medical management of ulcerative colitis has continued to evolve over more than half of a century. Perhaps, the important advance was the development of sulfasalazine, a drug initially used for the treatment of inflammatory joint disease and only later in the treatment of inflammatory bowel disease. Sulfasalazine was a combination designer drug consisting of sulfapyridine, a sulfa-containing antibacterial agent, and 5-amino-salicylate (5-ASA), an anti-inflammatory agent. Its value appeared to be its ability to target a therapeutic concentration of the 5-ASA component of the medication primarily in the colon, largely avoiding proximal small intestinal absorption. With increasing experience, however, it also became evident that many patients treated with sulfasalazine developed intolerance to the drug and, in some rare instances, serious drug-induced hypersensitivity reactions, largely to the sulfapyridine portion. As a result, a number of alternative forms of delivery of 5-ASA were developed consisting of either a similar sulfasalazine-like prodrug formulation requiring luminal destruction of an azo-bond releasing the 5-ASA or a pH-dependent 5-ASA packaging system that permitted release in the distal intestine, particularly in the colon. As a result, 5-ASA-containing medications continue to provide a valuable management tool for remission induction in mildly to moderately active distal or extensive ulcerative colitis, an additional option for more severely symptomatic disease and value for maintenance therapy with limited potential side effects, even with long-term use.

Proton pump inhibitors (PPIs) are among the most common classes of medications prescribed. Though they were previously thought of as safe, recent literature has shown risks associated with their use including increased risk for Clostridium difficile infection, pneumonia, and fractures. Due to these risks, it is important to determine if PPIs are being used appropriately. This review evaluates seven studies in hospitalized patients. Additionally, this review evaluates literature pertaining to recently discovered adverse reactions; all studies found PPIs are being overutilized. Findings highlight the importance of evaluating appropriate therapy with these agents and recommending discontinuation if a proper indication does not exist.

Adding proton pump inhibitors (PPIs) to endoscopic therapy has become the mainstay of treatment for peptic ulcer bleeding, with current consensus guidelines recommending high-dose intravenous (IV) PPI therapy (IV bolus followed by continuous therapy). However, whether or not high-dose PPI therapy is more effective than low-dose PPI therapy is still debated. Furthermore, maintaining pH ≥ 4 appears to prevent mucosal bleeding in patients with acute stress ulcers; thus, stress ulcer prophylaxis with acid-suppressing therapy has been increasingly recommended in intensive care units (ICUs). This review evaluates the evidence for the efficacy of IV pantoprazole, a PPI, in preventing ulcer rebleeding after endoscopic hemostasis, and in controlling gastric pH and protecting against upper gastrointestinal (GI) bleeding in high-risk ICU patients. The review concludes that IV pantoprazole provides an effective option in the treatment of upper GI bleeding, the prevention of rebleeding, and for the prophylaxis of acute bleeding stress ulcers.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain and altered bowel habits in the absence of specific organic pathology. Although the underlying pathogenesis of IBS is not well-understood, small intestinal bacterial overgrowth (SIBO) or other abnormalities in the gut flora is believed to contribute to the development of a subset of IBS cases. Rifaximin is a poorly absorbed antimicrobial with activity against enteric pathogens. A number of studies have shown a significant improvement in IBS symptoms with antibiotic therapy including rifaximin. In this review, we discuss the pharmacokinetics, in vitro susceptibility profile, and efficacy and safety data from clinical trials of rifaximin treatment of IBS.

Irritable bowel syndrome with constipation (IBS-C) affects approximately 5% of the population in western countries. The majority of those afflicted are women. Symptoms are often detrimental to the individual's quality of life and incur high healthcare costs to society. There is no evidence to support changes in lifestyle, laxatives or over the counter supplements. Tegaserod appeared to have promising results but was promptly removed from the market due to adverse cardiovascular events. In 2008, lubiprostone (Amitiza) was approved by the US Food and Drug Administration (FDA) for the treatment of women with IBS-C. It is thought to selectively activate type 2 chloride channels in the apical membrane of the intestinal epithelial cells leading to chloride secretion. As result, sodium and water are passively secreted generating peristalsis and laxation, without stimulating gastrointestinal smooth muscle. Several trials with predominantly female patients have shown it to be effective in the treatment of IBS-C. Overall lubiprostone was safe, well tolerated and associated with mostly benign side effects. Nausea and diarrhea were the most commonly reported. Though there are no head to head comparisons with other pharmacological agents, it is our opinion that lubiprostone should be tried as a first line pharmacotherapy for women with IBS-C at a dose of 8 μg BID. Thus far, lubiprostone offers a welcome approach to our narrow therapeutic armamentarium. Further understanding of its mechanism of action may provide additional insight into the pathophysiology of IBS-C.

Treatment with Anti-Tumor Necrosis Factor (anti-TNF) therapy has become a mainstay of therapy for patients with CD who are unresponsive to conventional medical management. Currently there are three anti-TNFα antibodies that have been approved by the US Food and Drug Administration for the treatment of CD, namely infliximab, adalimumab and certolizumab pegol (CZP). Several double blind placebo controlled trials determined that CZP is effective as induction and maintenance treatment in adult patients with CD regardless of their prior exposure to other anti-TNFα antibodies. This review discusses the efficacy of CZP and adherence to therapy with anti-TNFα antibodies in patients with CD.

Hepatic angiosarcoma (HAS) is a rare type of liver cancer that is often fatal, and arsenic and vinyl chloride monomer (VCM) are two major causal agents. Whereas Taiwan is an endemic area of liver cancer, epidemiologic data on HAS are limited. We reviewed the cases observed at a teaching hospital to evaluate the roles of VCM, arsenic, and viral hepatitis in the occurrence of HAS.

Cholangiocarcinoma is a heterogeneous disease with a poor outcome that accounts for 5%-10% of primary liver cancers. We characterized its genomic and genetic features and associated these with patient responses to therapy.

Aberrant Wnt/β-catenin signaling is widely implicated in numerous malignancies, including cancers of the gastrointestinal tract. Dysregulation of signaling is traditionally attributed to mutations in Axin, adenomatous polyposis coli, and β-catenin that lead to constitutive hyperactivation of the pathway. However, Wnt/β-catenin signaling is also modulated through various other mechanisms in cancer, including cross talk with other altered signaling pathways. A more complex view of Wnt/β-catenin signaling and its role in gastrointestinal cancers is now emerging as divergent phenotypic outcomes are found to be dictated by temporospatial context and relative levels of pathway activation. This review summarizes the dysregulation of Wnt/β-catenin signaling in colorectal carcinoma, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma, with particular emphasis on the latter two. We conclude by addressing some of the major challenges faced in attempting to target the pathway in the clinic.

Adult onset autoimmune enteropathy (AIE) is a rare condition characterized by diarrhea refractory to dietary therapy diagnosed in patients with evidence of autoimmune conditions. Auto-antibodies to gut epithelial cells and other tissues are commonly demonstrated. Despite increasing awareness, the pathogenesis, histologic, immunologic and clinical features of AIE remain uncertain. There remains controversy regarding the diagnostic criteria, the frequency and types of auto-antibodies and associated autoimmune conditions, and the extent and types of histologic and immunologic abnormalities. CD4+ T-cells are thought to at least responsible for this condition; whether other cell types, including B- and other T-cell subsets are involved, are uncertain. We present a unique case of AIE associated with a CD8+CD7- lymphocytosis and review the literature to characterize the histologic and immunologic abnormalities, and the autoantibodies and autoimmune conditions associated with AIE.

Regular use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been reported to reduce risks of esophageal adenocarcinoma (EAC) and esophagogastric junctional adenocarcinoma (EGJA). However, individual studies have been too small to accurately assess the effects of medication type, frequency, or duration of use. We performed a pooled analysis to investigate these associations.

Inflammasomes are multi-protein complexes that mediate activation of caspase-1, which promotes secretion of the proinflammatory cytokines interleukin-1β and interleukin-18 and pyroptosis, a form of phagocyte cell death induced by bacterial pathogens. Members of the Nod-like receptor family (including Nlrp1, Nlrp3, and Nlrc4), the DNA sensor Aim2, the adaptor apoptosis-associated speck-like protein (ASC), and pro-caspase-1 are important components of inflammasomes. Stimulation with specific microbial and endogenous molecules leads to inflammasome assembly and caspase-1 activation. Inflammasomes are believed to mediate host defense against microbial pathogens and tissue homeostasis within the intestine, and their dysregulation might contribute to inflammatory diseases and intestinal cancer. Improving our understanding of inflammasome signaling pathways could provide insights into the pathogenesis of many gastrointestinal disorders and the development of therapeutic targets and approaches to treat diseases such as inflammatory bowel diseases and gastrointestinal cancers.