Reviews & Analysis

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  • Oesophageal cancer is a global health problem with two main histological subtypes, oesophageal adenocarcinoma and oesophageal squamous cell carcinoma. This Review establishes the current epidemiology of oesophageal cancer, with a particular focus on the increasing incidence of oesophageal adenocarcinoma and its precursor, Barrett oesophagus.

    • Aaron P. Thrift
    Review Article
  • Although COVID-19 is a respiratory disease and its causative agent, SARS-CoV-2, principally infects the respiratory tract, extrapulmonary manifestations are observed. This Perspective explores the gastrointestinal symptoms associated with COVID-19 and the putative underlying mechanisms, discussing experimental evidence on SARS-COV-2 gastrointestinal infection and the potential for faecal–oral transmission.

    • Meng Guo
    • Wanyin Tao
    • Shu Zhu
    Perspective
  • Liver sinusoidal endothelial cells (LSECs) form the wall of the hepatic sinusoids and have essential roles in hepatic homeostasis. This Review describes the phenotypic dysregulations of LSECs in the context of liver disease and hepatocellular carcinoma, and provides an update of the role of LSECs as therapeutic targets.

    • Jordi Gracia-Sancho
    • Esther Caparrós
    • Rubén Francés
    Review Article
  • The therapeutic pipeline for nonalcoholic steatohepatitis (NASH) is expanding as insights into disease pathophysiology are gained. This Review summarizes progress in the development of NASH therapies, current and ongoing clinical trials, and potential challenges with emerging therapies.

    • Raj Vuppalanchi
    • Mazen Noureddin
    • Arun J. Sanyal
    Review Article
  • Inflammatory bowel disease (IBD) has emerged as a global disease, yet identifying those at higher risk of developing IBD remains challenging. A new study highlights the use of a multi-ethnic polygenic risk score to determine risk of inflammatory bowel disease in a large primary care population.

    • Ashwin N. Ananthakrishnan
    News & Views
  • Many molecular, physiological and behavioural processes display distinct daily rhythms that are directed by the circadian system. This Review summarizes knowledge about the diurnal regulation of gastrointestinal processes by circadian clocks present in the digestive tract and its accessory organs, including circadian control of digestion, motility, hormones, barrier function and the gut microbiota.

    • Anneleen Segers
    • Inge Depoortere
    Review Article
  • Although the role of the enteric nervous system in congenital enteric neuropathic disorders is well acknowledged, its role in systemic diseases is less understood. Here, the authors focus on diseases in which the enteric nervous system has so far not been considered to have a major role and on its emerging role in neurodegeneration, cancer and diabetes.

    • Beate Niesler
    • Stefanie Kuerten
    • Karl-Herbert Schäfer
    Review Article
  • A new study elevates our understanding of how the immune system regulates the pathogenesis of biliary atresia through a powerful single-cell approach. Cell-specific transcriptome analyses indicate key roles for macrophages, T cells and B cells in hepatobiliary injury of affected infants.

    • Abigail E. Russi
    • Jorge A. Bezerra
    News & Views
  • In this Review, Motta, Vergnolle and colleagues describe the organization of microorganisms into planktonic, biofilm and biofilm-dispersed forms in the gastrointestinal tract. The role of the host–biofilm relationship in gut homeostasis and disease is discussed.

    • Jean-Paul Motta
    • John L. Wallace
    • Nathalie Vergnolle
    Review Article
  • Locoregional therapies, defined as imaging-guided liver tumour-directed procedures, play a leading part in the management of hepatocellular carcinoma. This Review analyses data from randomized and uncontrolled studies reported with ablative and locoregional techniques and examines the expected effects of combinations with systemic treatments, exploring their distinct mechanisms of action.

    • Josep M. Llovet
    • Thierry De Baere
    • Riccardo Lencioni
    Review Article
  • In 2020, there have been substantial advances in nonalcoholic fatty liver disease mechanisms, diagnostics and treatment. Key developments include the identification of a cellular and tissue signature to provide new insights into pathophysiology, advancements in non-invasive diagnostics and publication of interim results of the first phase III trial to demonstrate improvement in hepatic fibrosis.

    • Manal F. Abdelmalek
    Year in Review
  • In 2020, important advances were made across three major frontiers of pancreatic ductal adenocarcinoma (PDAC) research: risk factors, therapeutic resistance and tumour recurrence. Pathophysiology of obesity-mediated PDAC initiation was elucidated, novel stromal mechanisms of therapeutic resistance were unveiled and the genetic evolution of recurrent PDAC under therapeutic pressures was tracked in human samples.

    • Tejeshwar Jain
    • Vikas Dudeja
    Year in Review
  • In 2020, combination treatments have pushed the efficacy of systemic therapy for hepatocellular carcinoma (HCC) to an unprecedented high, providing a solid base for the future pursuit of further improved, highly efficacious systemic therapies for HCC.

    • Ann-Lii Cheng
    Year in Review
  • Although fermented foods have been consumed for thousands of years, a clear definition has been lacking. This Consensus Statement outlines a definition for the term ‘fermented foods’ as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in September 2019.

    • Maria L. Marco
    • Mary Ellen Sanders
    • Robert Hutkins
    Consensus Statement Open Access
  • In 2020, studies have used pure cultures of members of the gut microbiota to establish a molecular chain of causation for the role of these key bacteria in aggravating or alleviating cancer and metabolic diseases. These studies highlight the need for microbiome studies to move from associations back to cultures to demonstrate causality.

    • Liping Zhao
    • Naisi Zhao
    Year in Review
  • The prevalence of nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) is projected to continue to increase worldwide. In this Review, Huang, El-Serag and Loomba discuss the global epidemiology and risk factors for NAFLD-related HCC, and propose strategies to tackle this problem.

    • Daniel Q. Huang
    • Hashem B. El-Serag
    • Rohit Loomba
    Review Article
  • Human microphysiology systems (MPS) have evolved as experimental model systems. This Review explores these so-called organ-on-a-chip systems and the role of biomimetic human liver MPS in drug development and precision medicine, providing insights into their design and use as models of liver physiology and disease.

    • Albert Gough
    • Alejandro Soto-Gutierrez
    • D. Lansing Taylor
    Review Article
  • Key studies published in 2020 demonstrate that an impaired intestinal barrier precedes clinical diagnosis of inflammatory bowel disease (IBD) by years. Furthermore, studies identify novel regulators of the intestinal barrier, including intestinal macrophages and diurnal variations of diet–microbiome interactions, which could be future therapeutic strategies for IBD.

    • Saurabh Mehandru
    • Jean-Frederic Colombel
    Year in Review
  • One of the most pleasurable, yet dangerous, activities of our daily life is eating. But once food has been swallowed, all we can do is to trust our gut. Several remarkable studies published in 2020 have expanded our knowledge on how the gut is intertwined with essential behaviours beyond food.

    • Diego V. Bohórquez
    Year in Review