Reviews & Analysis

The combination of increasing disease prevalence and the prospect of approved pharmacological treatments has made the development of noninvasive biomarkers for NAFLD and NASH a research priority. In this Review, the authors comprehensively summarize the features of current and potential biochemical, imaging and genetic biomarkers.

Liver sinusoidal endothelial cells (LSECs) represent the most abundant non-parenchymal hepatic cell population. In this Review, the authors explore the key roles that LSECs have in regulating hepatic immunity and their contribution to immune-mediated disease, liver fibrosis and carcinogenesis.

Emerging data implicate diet as a crucial factor in the development and progression of IBD. Here, the authors discuss epidemiological, animal, gene–environment interaction and gut microbiome studies that have investigated the role of diet in the aetiopathogenesis of IBD.

Direct-acting antiviral agents (DAAs) have revolutionized the management of chronic hepatitis C, but their use in acute infection is unclear. This Review outlines the epidemiology, diagnosis and management of acute HCV infection, providing insights into the use of DAAs in at-risk populations (such as people who inject drugs).

Infant colic is a source of major distress for caregivers and the affected infant. In this Review, the authors explore the evidence for gastrointestinal, psychosocial, microbial and neurogenic factors in the pathogenesis of the condition. Diagnostic and management strategies are also discussed.

Recurrence of hepatocellular carcinoma after resection or ablation with curative intent is common and not prevented by direct-acting antiviral agent (DAA) therapy for hepatitis C. Owing to multiple methodological inconsistencies, available studies fail to answer whether DAA therapy anticipated risk of severe tumour recurrence: a prospective randomized study might serve the purpose.

In a new study, Maier et al. reveal that non-antibiotic drugs intended to target human cells have off-target effects on the growth of human gut bacteria at clinically relevant concentrations. These results emphasize the need for a new field of metagenomic toxicology aimed at a more comprehensive understanding of the toxicity of compounds for humans and their associated microbial communities.

Attention has turned to the gut microbiota in liver disease, including alcoholic and nonalcoholic fatty liver disease and hepatocellular carcinoma. This Review describes gut–liver communications, including evidence from animal and human studies, compares conditions within the liver disease spectrum and highlights key points for designing microbiome-based studies for liver disease research.

Nonalcoholic steatohepatitis is the progressive form of nonalcoholic fatty liver disease, one of the most common chronic liver diseases. In this Review, the authors comprehensively discuss the key factors that trigger hepatic inflammation, as well as the pathways involved in inflammation resolution.

For decades, the 5-year survival for pancreatic cancer remained largely static. In this Review, the authors explore the improvements in pancreatic cancer treatment obtained in the past few years and discuss key questions related to the future development of new therapies.

Colorectal cancer screening can save lives but there is a need for targeted, personalized screening. A new study examines an individual risk assessment based on family history, lifestyle, environmental and genetic factors, but faecal haemoglobin levels and their change over time can also help to further identify patients at high risk.

The efficacy of Helicobacter pylori eradication therapy for the prevention of preneoplastic lesions in gastric cancer remains controversial. A new placebo-controlled trial and a large-scale observational study tackle this problem and show the positive effects of eradication therapy.

Cardiovascular disease is the leading cause of death in NAFLD. In this Review, the authors explore the evidence that NAFLD affects not only the coronary arteries but also all other cardiac structures, thereby potentially increasing risk of cardiomyopathy, cardiac arrhythmias, conduction defects and valvular calcification.

Biological network models can provide a scaffold for studying the biological pathways operating in connection with disease development. Here, the authors review how biological network models can integrate multiomics data to advance our understanding of complex liver diseases, which might lead to improved treatment strategies.

Mechanical forces are important for normal gastrointestinal development and function. Now, He et al. have discovered a population of Drosophila midgut epithelial enteroendocrine cell (EEC) precursors that express the mechanosensitive ion channel Piezo, which generates a calcium influx that drives EEC differentiation and proliferation in response to physiological mechanical stimuli.

Rapid urbanization in the developing world has been associated with an increasing incidence of several autoimmune diseases. This Perspective discusses the effect of urbanization and its surrogates on the gut microbiome in both human health and IBD and how such changes might be associated with the development of IBD.

Exome sequencing of patients with Crohn’s disease (CD) of Ashkenazi Jewish descent and genotyping of large case–control cohorts has identified new CD risk and protective variants of LRRK2, the most common genetic determinant of Parkinson disease. These findings provide new insights into the pathophysiology of these two seemingly unrelated disorders.

Psychosocial risk factors (often linked to the gut–brain axis) are prevalent across different gastrointestinal disorders. Here, Keefer discusses the emerging field of psychogastroenterology and how behavioural medicine and the promise of positive psychology (resilience, optimism and self-regulation) could improve patient management.

Faecal incontinence and evacuation disorders are common and substantially impair quality of life. In this Consensus Statement, the authors describe recommended tests for the evaluation of anorectal function and the clinical relevance of these tests in the management of patients to help guide the practising clinician.

In a prospective study of adults with Crohn’s disease or ulcerative colitis, Gracie and colleagues have found evidence for the bi-directional relationship between inflammatory bowel disease (IBD) activity and symptoms of psychological disorders. This study represents an important milestone in our understanding of how the brain and gut interact in IBD.