Articles in 2018

In 2018, advances were made in immunotherapy for colorectal cancers with microsatellite instability but, by contrast, immunotherapy studies in microsatellite-stable colorectal cancer had disappointing results. However, novel insights into the tumour microenvironment barriers that might limit therapeutic efficacy were identified, thereby offering new strategies.

Liver microcirculatory dysfunction is one of the key mechanisms that promotes the progression of chronic liver disease. In this Review, the authors explore the role of liver microcirculatory dysfunction in cirrhotic portal hypertension, the preclinical models used to study liver circulation and potential therapeutics.

In 2018, there have been substantial advances in our understanding of the risk factors for advanced liver disease in nonalcoholic fatty liver disease, including genetic variants and the gut microbiota. Promising results have also arisen from drugs targeting metabolic pathways involved in the progression of liver damage.

In 2018, key studies shaped the way we think about environmental factors and their influence on the gut microbiota. These data highlight a new-found appreciation for the role of diet in modifying the gut microbiome and fortifying the intestinal barrier, which ultimately might lead to better treatments for chronic metabolic diseases.

Deciphering the complex circuitry of liver homeostasis and repair is required to improve regenerative therapies for hepatic diseases. Studies in 2018 have identified subsets of hepatic cells that have unique reparative abilities and clarified the role of biomechanical forces and hepatobiliary reprogramming as sustainable modes of tissue repair.

Fatigue is an important problem for patients with IBD, but little is known about its pathophysiology. In this Review, the authors explore the epidemiology, putative mechanisms and optimal management of this symptom.

Cell-based therapies for the treatment of perianal Crohn’s disease have well-established safety profiles and improved efficacy compared with conventional therapy. However, stem cells are not a homogeneous product and questions remain before we can optimize clinical trials of these treatments and achieve best patient outcomes.

The liver is a key metabolic organ, and alterations to hepatic metabolism are important for the development of disease. In this Review, the authors explore the central roles of peroxisome proliferator-activated receptor-γ coactivators (PGC1s) in physiological and pathophysiological settings, with a focus on nonalcoholic fatty liver disease and liver cancer.

In this Review, Yadav and Petrov discuss the most up-to-date epidemiological data on acute and chronic pancreatitis. The authors also present strategies to reduce the burden of pancreatitis and its associated metabolic disorders.

The pathophysiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis is not yet completely understood but innate immunity is a major factor. In this Review, the evidence for macrophage involvement in the development of liver steatosis, inflammation and fibrosis is discussed.

This Review outlines the current understanding of IL-12 and IL-23 biology in IBD, as well as the roles of major downstream cytokines, including IL-17. The authors also discuss how emerging knowledge influences the development of therapeutic strategies in IBD.

Important studies published in 2018 highlight novel therapeutic strategies along the disease course of IBD, including potential specific dietary modifications at early stages and treatment with adipose-derived stem cells in perianal Crohn’s disease. A treat-to-target approach that involves proactive serial monitoring of inflammatory biomarkers can assist in timely treatment escalation and promises improved patient outcomes.

The Wnt–β-catenin pathway is a highly conserved pathway that regulates embryogenesis and key regenerative processes in adult organs. Here, the authors discuss the role of Wnt–β-catenin signalling in liver development and disease, including in liver cancer, NAFLD and liver fibrosis.

Redox signalling in the gastrointestinal mucosa is held in an intricate balance. This Review addresses both the spectrum and intensity of redox activity pertaining to host–immune and host–microbiota crosstalk during homeostasis and disease processes in the gastrointestinal tract.

The intestinal epithelium undergoes constant replenishment, fuelled by continuously dividing stem cells residing in crypts. In this Review, Gehart and Clevers discuss the signals, cell types and mechanisms that control intestinal stem cell homeostasis and explore how imbalance in key signalling pathways can cause disease.

Work during the past two decades has highlighted how HIV contributes to hepatic inflammation and fibrosis, leading to changes in the timing of antiretroviral therapy initiation and to improved diagnosis and management of liver disease in patients with HIV. As this population ages, clinician vigilance with early detection of emerging liver disease will be critical.