Reviews & Analysis

Chronic HCV infection is a leading cause of liver-related morbidity and mortality. In 2011, treatment options for patients infected with HCV genotype 1 changed dramatically with the approval of two nonstructural protein 3 protease inhibitors—boceprevir and telaprevir—by the FDA and the European Medicines Agency.

Interest in the gut microbiota has escalated with growing appreciation of the role of indigenous microbes in the health of the host and in the pathogenesis of several intestinal and extraintestinal disorders. The microbiota has become a plausible target for drug and dietary therapy and a repository from which bioactive agents or new drugs can be mined.

The gut microbiota is now widely recognized to have a central role in human health and disease, and can be manipulated to improve an individual's health. Fecal microbiota transplantation (FMT), as outlined in this Review, is one such approach to resolve dysbiosis of the gut microbiota and has therapeutic potential in a range of gastrointestinal diseases. The authors provide a broad overview of FMT and a timely update on the latest advances.

Pelvic floor dysfunction encompasses a range of symptoms that are presented to specialists across multiple disciplines. In this Perspectives Hans Peter Dietz provides an interdisciplinary overview of imaging pelvic floor dysfunction. Modern pelvic floor imaging techniques, including MRI, defecation proctography and ultrasound are discussed as well as their potential application to improving management of pelvic floor disorders.

Treating pancreatic cancer can be challenging, as patients often have a poor prognosis and chemoresistance is common. As pancreatic cancer is fundamentally a genetic disease, the authors of this Review emphasize the complex mutational heterogeneity of pancreatic ductal adenocarcinomas and the importance of moving towards a model of tailoring therapies to the specific genetic characteristics of individual tumors.

Autoimmune pancreatitis (AIP) is becoming increasingly recognized as a unique form of chronic pancreatitis. Its diagnosis, based on clinical and pathological parameters, is challenging. AIP is currently divided clinicopathologically into type 1 and type 2. Histological diagnostic criteria for type 1 and type 2 AIP have now been proposed by an international consensus study.

Neurogastroenterology encompasses intrinsic and extrinsic neural processes that regulate gut functions, sensation and related behaviors such as ingestion. In 2011, key advances were made in understanding gut–brain interactions, visceral sensation, serotonin signaling, neurogenesis and neuromuscular transmission.

As a result of its multifactorial nature, IBS poses a major therapeutic challenge in relation to what factors are best targeted. Hypnotherapy offers a unique solution to this problem by virtue of its ability to modify a wide range of pathophysiological processes to bring about symptomatic improvement.

Algorithms can predict the risk of rebleeding and mortality in patients with upper gastrointestinal bleeding, but not the risk of rebleeding following endoscopic treatment in patients with ulcers. A recent meta-analysis has addressed this issue, and could facilitate the development of methods to predict rebleeding and endoscopic treatments to reduce rebleeding.

Endoscopic palliation of malignant biliary obstruction or gastric outlet obstruction can be technically challenging and might require other interventions in some patients. Results from two recent studies suggest that nitinol self-expanding metal stents are safe and effective for both indications and might decrease the need for other interventions in these patients.

For colorectal cancer screening, the issue is no longer whether the fecal immunochemical test (FIT) is preferable to the guaiac fecal occult blood test, but how best to use the FIT. Using the OC-Sensor^™ FIT with a hemoglobin cut-off level of 50 ng/ml could offer the best cost-effectiveness ratio compared with nonscreening settings.

This Review describes interactions between intrahepatic cholangiocarcinoma cells and the surrounding stroma, with a focus on myofibroblastic cells. A 'human-like' orthotopic rat model and a new organotypic culture system have been developed, which can be used to test new therapies. Novel combination approaches to treatment that target both the cancer cells and cancer-promoting stromal cells are discussed.

Gastroesophageal reflux disease (GERD) is a chronic disorder that occurs when refluxate from the stomach comes into contact with the esophageal mucosa, typically causing symptoms such as heartburn and regurgitation. This Review focuses on the mucosal pathogenesis of GERD and describes new concepts in the role of mucosal inflammation in disease development in relation to the current model of GERD pathogenesis.

MRI could be used by clinicians as an effective tool to monitor patients with Crohn's disease. In this Review, Gionata Fiorino, Cristiana Bonifacio, Luca Balzarini, Alberto Malesci and Silvio Danese discuss the development of objective MRI-based scores that enable evaluation of the extent of intestinal damage. They also speculate on the generation of a new 'damage-driven' treatment paradigm—in which imaging is used to monitor intestinal damage and medication use is targeted to prevent the accumulation of further damage

Accurate estimation of standard liver volume (SLV) is one of the key factors for successful liver transplantation. Contrary to some misconceptions, SLV was developed for the sake of the recipient and not for the donor in living donor liver transplantation. A recent study evaluated the accuracy of five formulas for estimation of SLV, and investigated the effect of liver steatosis on errors in estimation.

Crohn's disease is a life-long illness, with patients increasingly being exposed to diagnostic medical radiation. Diagnostic strategies are being re-evaluated after concerns were raised over the long-term effects of medical radiation. A recent study explored the cost-effectiveness of a magnetic resonance enterography program in patients with Crohn's disease, which could reduce the risk of radiation-induced neoplasia.

Mucins have an important role in protecting the esophagus from the effects of acids, pepsins and other noxious materials. Mucins are altered in patients with GERD, which could be key to the development of new therapeutics. This Perspectives will cover studies about mucin secretion in the esophagus in health and disease states, and its potential role as a protective substance.

Currently, vaccines are not widely used in the control of cholera, but new-generation orally administered vaccines may well become important tools in the public health armamentarium against this disease. This Review focuses on selected aspects of the disease, its pathogenesis and immunology, clinical features, epidemiology and treatment, and summarizes the status of new-generation cholera vaccines.

Pediatric liver transplantation is a major surgical challenge, especially in very small patients (≤5 kg), and existing literature on low-body-weight transplant recipients is limited. Two new studies discuss the possibilities and limitations of liver transplantation in very young infants and demonstrate encouraging results for liver transplantation in infancy.

An ideal diagnostic test should be quick, reliable and noninvasive. Fecal calprotectin is considered a marker of intestinal inflammation and has proven to be an effective test for IBD, but is fecal calprotectin a useful diagnostic tool when assessing patients with cirrhosis?