Latest Reviews

  • Review Article |

    The hepatic consequence of metabolic syndrome and obesity, nonalcoholic fatty liver disease (NAFLD), underlies many cases of hepatocellular carcinoma (HCC). In this Review, the authors discuss NAFLD-associated HCC, including its epidemiology, key features that promote hepatocarcinogenesis and the management of HCC in patients with obesity.

    • Quentin M. Anstee
    • , Helen L. Reeves
    • , Elena Kotsiliti
    • , Olivier Govaere
    •  & Mathias Heikenwalder
  • Perspective |

    Nonalcoholic fatty liver disease (NAFLD) was first described four decades ago, but it is increasingly important owing to its high prevalence in the general population. This Perspective provides an overview on the development of knowledge related to NAFLD, focusing on landmark findings.

    • Arun J. Sanyal
  • Review Article |

    The introduction of white light imaging capsule endoscopy has motivated research to improve its diagnostic capabilities through integration with other sensing modalities. In this Review, the authors summarize studies on non-white light imaging devices, such as those using optical coherence tomography, ultrasonography or biophysical measurements

    • Gerard Cummins
    • , Benjamin F. Cox
    • , Gastone Ciuti
    • , Thineskrishna Anbarasan
    • , Marc P. Y. Desmulliez
    • , Sandy Cochran
    • , Robert Steele
    • , John N. Plevris
    •  & Anastasios Koulaouzidis
  • Review Article |

    Key hepatic functions are expressed non-uniformly across liver lobules, a phenomenon termed zonation. Here, Ben-Moshe and Itzkovitz discuss the principles of liver zonation, the intrinsic and extrinsic factors that dictate zonation patterns and new genomic approaches for studying zonation of parenchymal and non-parenchymal cells

    • Shani Ben-Moshe
    •  & Shalev Itzkovitz
  • Review Article |

    Neonatal cholestasis is a group of disorders of impaired bile flow characterized by conjugated hyperbilirubinaemia that can be fatal if not treated rapidly. In this Review, aetiologies, algorithms for evaluation and current and emerging therapeutic options for neonatal cholestasis are discussed.

    • Amy G. Feldman
    •  & Ronald J. Sokol
  • Review Article |

    Ganesh et al. describe the rationale for using immunotherapy in select patients with colorectal cancer, discuss clinical findings supporting its use and highlight current strategies and future directions for expanding the scope of immunotherapy in this disease.

    • Karuna Ganesh
    • , Zsofia K. Stadler
    • , Andrea Cercek
    • , Robin B. Mendelsohn
    • , Jinru Shia
    • , Neil H. Segal
    •  & Luis A. Diaz Jr
  • Review Article |

    Cholangiocytes, which line the intrahepatic and extrahepatic bile ducts, are specialized cells that regulate bile production and homeostasis. Here, the authors discuss the role of cholangiocytes in development and liver regeneration, inflammation and fibrosis and their interactions with the immune system.

    • Jesus M. Banales
    • , Robert C. Huebert
    • , Tom Karlsen
    • , Mario Strazzabosco
    • , Nicholas F. LaRusso
    •  & Gregory J. Gores
  • Review Article |

    Disease presentation and progression within and across IBD are highly heterogeneous, particularly in Crohn’s disease. Here, the authors summarize genomic, epigenomic and gut microbiota studies in adult and paediatric patients that have identified different IBD subtypes.

    • Terrence S. Furey
    • , Praveen Sethupathy
    •  & Shehzad Z. Sheikh
  • Review Article |

    Cancer-associated fibroblasts are critical components of the tumour mesenchyme. In this Review, the authors outline the emerging understanding of gastrointestinal cancer-associated fibroblasts with a particular emphasis on their origin and heterogeneity, as well as their function in cancer biology.

    • Hiroki Kobayashi
    • , Atsushi Enomoto
    • , Susan L. Woods
    • , Alastair D. Burt
    • , Masahide Takahashi
    •  & Daniel L. Worthley
  • Review Article |

    This Review summarizes current knowledge concerning the molecular subtyping of pancreatic cancer and explores future strategies using molecular taxonomy to guide therapeutic development and therapy with the overall goal of improving outcomes for this disease.

    • Eric A. Collisson
    • , Peter Bailey
    • , David K. Chang
    •  & Andrew V. Biankin
  • Review Article |

    In this Review, the authors explore potential applications of big data in IBD research, including predictive models of disease course and response to therapy, characterization of disease heterogeneity, drug safety and development, precision medicine and cost-effectiveness of care.

    • Pablo Olivera
    • , Silvio Danese
    • , Nicolas Jay
    • , Gioacchino Natoli
    •  & Laurent Peyrin-Biroulet
  • Review Article |

    Alcoholic liver disease (ALD) is a leading cause of morbidity and mortality worldwide. Here, Bajaj discusses clinical studies on the gut microbiota in individuals with ALD and explores the specific alterations in the gut–liver–brain axis that might alter patient outcomes.

    • Jasmohan S. Bajaj
  • Review Article |

    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.

    • Jordi Gracia-Sancho
    • , Giusi Marrone
    •  & Anabel Fernández-Iglesias
  • Review Article |

    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.

    • Nienke Z. Borren
    • , C. Janneke van der Woude
    •  & Ashwin N. Ananthakrishnan
  • Review Article |

    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.

    • Elena Piccinin
    • , Gaetano Villani
    •  & Antonio Moschetta
  • Review Article |

    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.

    • Maxim S. Petrov
    •  & Dhiraj Yadav
  • Review Article |

    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.

    • Konstantin Kazankov
    • , Simon Mark Dahl Jørgensen
    • , Karen Louise Thomsen
    • , Holger Jon Møller
    • , Hendrik Vilstrup
    • , Jacob George
    • , Detlef Schuppan
    •  & Henning Grønbæk
  • Review Article |

    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.

    • Alexander R. Moschen
    • , Herbert Tilg
    •  & Tim Raine
  • Review Article |

    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.

    • Maria J. Perugorria
    • , Paula Olaizola
    • , Ibone Labiano
    • , Aitor Esparza-Baquer
    • , Marco Marzioni
    • , Jose J. G. Marin
    • , Luis Bujanda
    •  & Jesus M. Banales
  • Review Article |

    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.

    • Eric L. Campbell
    •  & Sean P. Colgan
  • Review Article |

    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.

    • Helmuth Gehart
    •  & Hans Clevers
  • Review Article |

    Electric stimulation of nerves might be useful for various gastrointestinal disorders. In this Review, the authors discuss neuromodulation therapies in relation to current knowledge of the nerve circuitry, provide insights into possible mechanisms and explore reasons for limited success and how effectiveness might be improved.

    • Sophie C. Payne
    • , John B. Furness
    •  & Martin J. Stebbing
  • Review Article |

    An association between obesity and many cancers exists, but how obesity affects the tumour microenvironment remains poorly understood. This Review explores key pathways linking visceral obesity and gastrointestinal cancer, including inflammation, hypoxia, stromal and immune cell function, metabolism and angiogenesis.

    • Jacintha O’Sullivan
    • , Joanne Lysaght
    • , Claire L. Donohoe
    •  & John V. Reynolds
  • Review Article |

    Current nutritional approaches to prevent and treat various diseases have limited effectiveness. Here, Zmora et al. review the major principles underlying effects of dietary constituents on the gut microbiota, resolving aspects of the diet–microbiota–host crosstalk, and present the promises and challenges of incorporating microbiome data into dietary planning.

    • Niv Zmora
    • , Jotham Suez
    •  & Eran Elinav
  • Review Article |

    Cell death is a fundamental driver of liver disease progression. Here, the authors summarize the specific roles of apoptosis and necroptosis in different liver disease aetiologies, including nonalcoholic fatty liver disease, nonalcoholic steatohepatitis and liver cancer.

    • Robert F. Schwabe
    •  & Tom Luedde
  • Review Article |

    In this Review, the authors discuss how the gut microbiota might incite food sensitivity. They focus on direct and indirect mechanisms involving microorganisms and how increased understanding of these mechanisms will help the development of therapeutic strategies for food sensitivities.

    • Alberto Caminero
    • , Marlies Meisel
    • , Bana Jabri
    •  & Elena F. Verdu
  • Review Article |

    Metabolic homeostasis is orchestrated partly in response to nutrient-dependent vagal afferent signals transmitted from the gut to the central nervous system. This Review highlights our understanding of the vagal afferent system and its role in regulation of appetite and glucose homeostasis.

    • T. M. Zaved Waise
    • , Helen J. Dranse
    •  & Tony K. T. Lam
  • Review Article |

    Metabolic surgery is the best treatment for long-term weight loss maintenance and comorbidity control. In this Review, the authors discuss how gut physiology adapts to these procedures and the consequent effects on food intake, weight loss, liver disease and cancer.

    • Piriyah Sinclair
    • , Donal J. Brennan
    •  & Carel W. le Roux
  • Review Article |

    Liver diseases exert a substantial disease burden across the Asia–Pacific region. In this Review, the authors explore the epidemiological trends in the most common liver diseases in the region, including HBV infection, HCV infection and nonalcoholic fatty liver disease, and discuss implications for preventive measures.

    • Martin C. S. Wong
    • , Jason L. W. Huang
    • , Jacob George
    • , Junjie Huang
    • , Colette Leung
    • , Mohammed Eslam
    • , Henry L. Y. Chan
    •  & Siew C. Ng
  • Review Article |

    Intervention studies have helped characterize the potential mechanisms linking obesity and risk of gastrointestinal cancers in humans. Here, the authors explore the findings of these trials and detail how the key pathways involved, including inflammation, adipokines and metabolic dysfunction, might modulate carcinogenesis in gastrointestinal tissues.

    • Cornelia M. Ulrich
    • , Caroline Himbert
    • , Andreana N. Holowatyj
    •  & Stephen D. Hursting
  • Review Article |

    In this Review, the authors summarize how various interactions at the gastrointestinal epithelium regulate gut physiology. They also discuss how neuroimmunophysiology has advanced the understanding of gastrointestinal pathophysiology with the potential to reveal novel therapies for disorders such as IBS and IBD.

    • Keith A. Sharkey
    • , Paul L. Beck
    •  & Derek M. McKay
  • Review Article |

    Current approaches to manage decompensated cirrhosis are based on targeted strategies aimed at preventing or treating specific complications of the disease. Here, Bernardi and Caraceni discuss the shift in focus from individual treatments targeting individual complications to disease-modifying agents able to slow the progression of decompensation.

    • Mauro Bernardi
    •  & Paolo Caraceni
  • Review Article |

    Intraepithelial T cells (IETs) are a unique collection of T cells located at the epithelial barrier. This Review highlights the role of these cells in gut homeostasis and disease, including coeliac disease and IBD. Targeting of IETs in therapeutic interventions is also discussed.

    • Lisanne Lutter
    • , David P. Hoytema van Konijnenburg
    • , Eelco C. Brand
    • , Bas Oldenburg
    •  & Femke van Wijk
  • Review Article |

    Excess adiposity is a risk factor for many cancers of the gastrointestinal system. In this Review, the authors examine the epidemiological evidence of associations between obesity and gastrointestinal cancer risk and explore the potential mechanisms underlying these relationships.

    • Neil Murphy
    • , Mazda Jenab
    •  & Marc J. Gunter
  • Review Article |

    Multiple methods exist to induce liver disease and hepatocellular carcinoma formation in mice. This Review provides an overview of different mouse models of hepatocellular carcinoma, discussing approaches to help choose an appropriate model and highlighting specific concepts for immunotherapy research.

    • Zachary J. Brown
    • , Bernd Heinrich
    •  & Tim F. Greten
  • Review Article |

    Gastrointestinal symptoms related to motility and function are common. A broad overview on the clinical measurements and tests of gastrointestinal motility, function and sensitivity is provided in this Review, with insights into applications for patient management.

    • Mark R. Fox
    • , Peter J. Kahrilas
    • , Sabine Roman
    • , C. Prakash Gyawali
    • , S. Mark Scott
    • , Satish S. Rao
    • , Jutta Keller
    •  & Michael Camilleri
  • Review Article |

    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.

    • Vincent Wai-Sun Wong
    • , Leon A. Adams
    • , Victor de Lédinghen
    • , Grace Lai-Hung Wong
    •  & Silvia Sookoian
  • Review Article |

    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.

    • Shishir Shetty
    • , Patricia F. Lalor
    •  & David H. Adams
  • Review Article |

    Mitochondria have many key roles, including in cellular metabolism and cell fate decision. This Review explores the role of mitochondrial function and metabolism in homeostasis of the intestinal epithelium in health and disease, highlighting the involvement of the mitochondrial unfolded protein response.

    • Eva Rath
    • , Antonio Moschetta
    •  & Dirk Haller
  • Review Article |

    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.

    • Hamed Khalili
    • , Simon S. M. Chan
    • , Paul Lochhead
    • , Ashwin N. Ananthakrishnan
    • , Andrew R. Hart
    •  & Andrew T. Chan
  • Review Article |

    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).

    • Marianne Martinello
    • , Behzad Hajarizadeh
    • , Jason Grebely
    • , Gregory J. Dore
    •  & Gail V. Matthews
  • Review Article |

    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.

    • Judith Zeevenhooven
    • , Pamela D. Browne
    • , Monique P. L’Hoir
    • , Carolina de Weerth
    •  & Marc A. Benninga
  • Review Article |

    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.

    • Anupriya Tripathi
    • , Justine Debelius
    • , David A. Brenner
    • , Michael Karin
    • , Rohit Loomba
    • , Bernd Schnabl
    •  & Rob Knight
  • Review Article |

    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.

    • Susanne Schuster
    • , Daniel Cabrera
    • , Marco Arrese
    •  & Ariel E. Feldstein