Liver diseases articles within Nature Reviews Gastroenterology & Hepatology

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  • Review Article |

    This Review discusses the molecular heterogeneity of hepatocellular carcinoma, the intrinsic and extrinsic factors that stimulate tumour evolution and how this information can be leveraged to improve the clinical management of patients with this disease.

    • Amanda J. Craig
    • , Johann von Felden
    •  & Augusto Villanueva

  • Year in Review |

    Advances have been made in the field of nonalcoholic fatty liver disease in 2019. One paper highlights the role of gut microbiota in hepatocellular carcinoma (HCC) pathogenesis, another presents a noninvasive algorithm for detecting advanced liver fibrosis and another suggests a potential novel approach to treating nonalcoholic steatohepatitis and suppressing HCC development.

    • Christopher D. Byrne
    •  & Giovanni Targher

  • News & Views |

    A new study demonstrates a novel role for an endocannabinoid in promoting hepatocyte steatosis. The study describes a mode of bidirectional communication between the alcohol-injured hepatocyte and the glutamate-activated hepatic stellate cell. This intercellular communication represents a novel targetable pathogenic mechanism that could lead to new strategies to prevent fatty liver disease progression to cirrhosis.

    • Josepmaria Argemi
    •  & Ramon Bataller

  • Review Article |

    This Review discusses the genetics of nonalcoholic fatty liver disease (NAFLD), including evidence of shared genetic modifiers and possible pleiotropic effects between NAFLD and other liver diseases or metabolic disorders. The translational implications and future challenges are also discussed.

    • Mohammed Eslam
    •  & Jacob George

  • Review Article |

    Innate immune responses are currently seen as a key element driving hepatic inflammation in nonalcoholic steatohepatitis. However, this Review discusses the increasing evidence pointing to the role of adaptive immunity as an additional factor promoting liver inflammation and driving disease progression.

    • Salvatore Sutti
    •  & Emanuele Albano

  • Review Article |

    Multiple therapeutic approaches are being developed to achieve sustained, off-treatment suppression of HBV. In this Review, the authors examine T cell and B cell responses to HBV and the potential for immunotherapies to restore or release endogenous adaptive immunity by direct or indirect approaches.

    • Mala K. Maini
    •  & Alice R. Burton

  • News & Views |

    Living donor liver transplantation is a proven option for end-stage liver disease. In a new study, a pioneering multi-organ transplantation programme in Canada critically reviews the motivations and facilitators of anonymous adult living liver donors over a 12-year period, providing insights into how we can push forward ethical living organ donation for transplantation.

    • Robert A. Fisher

  • Review Article |

    The design of clinical trials for hepatocellular carcinoma is complicated by a number of obstacles. In this Review, the authors discuss the advances in systemic therapy for hepatocellular carcinoma and critically discuss trial designs in the context of past successes and failures.

    • Jordi Bruix
    • , Leonardo G. da Fonseca
    •  & María Reig

  • Comment |

    Late presentation to hepatitis B virus and hepatitis C virus care is common, hindering global efforts to reduce the morbidity and mortality associated with liver disease. Models of care promoting and simplifying early testing of viral hepatitis are needed if we are to eliminate viral hepatitis as a major public health threat by 2030.

    • Jeffrey V. Lazarus
    • , Camila Picchio
    •  & Maria Buti

  • News & Views |

    A new study involving integrative genomic and transcriptomic analysis of dual hepatocellular–intrahepatic cholangiocarcinoma tumours has identified distinct subtypes that display different clinical and molecular features, and that could be used to guide therapeutic decisions.

    • Patricia Munoz-Garrido
    •  & Pedro M. Rodrigues

  • Review Article |

    Nonalcoholic fatty liver disease (NAFLD) has become the most common form of chronic liver disease in children and adolescents. In this Review, the authors summarize current knowledge and new advances related to the epidemiology, pathogenesis and management of paediatric NAFLD.

    • Valerio Nobili
    • , Anna Alisi
    •  & Naim Alkhouri

  • Review Article |

    Telomerase is a key enzyme for cell survival that prevents telomere shortening. In this Review, the roles of telomeres and telomerase in cirrhosis and liver carcinogenesis are discussed, in addition to their potential in clinical practice as biomarkers and therapeutic targets.

    • Jean-Charles Nault
    • , Massih Ningarhari
    •  & Jessica Zucman-Rossi

  • News & Views |

    A new study shows that a real-world care pathway for patients with NAFLD in primary care can increase the detection of patients with clinically significant liver disease and decrease referrals for patients who could be managed in the community.

    • Patricia C. Valery
    •  & Elizabeth E. Powell

  • News & Views |

    A new study provides evidence that platelets exert potent inflammatory effects and play a central part in the progression from simple steatosis to nonalcoholic steatohepatitis. The results from this and other studies raise important questions regarding the role of platelets in the development of hepatocellular carcinoma in individuals with fatty liver disease.

    • Laurence P. Diggs
    •  & Tim F. Greten

  • 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
    •  & 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

  • News & Views |

    A new study of a fibroblast growth factor 19 analogue in patients with primary sclerosing cholangitis (PSC) provides provocative results. The data challenge alkaline phosphatase levels as the appropriate surrogate end point in PSC trials and highlight alternatives, urging efforts to identify better clinical end points for this disease.

    • Alessio Gerussi
    •  & Pietro Invernizzi

  • News & Views |

    Over the past decade, many studies have revealed the importance of the gut microbiome in disease development and treatment, including in cancer. Because both host genetics and the gut microbiome can influence host phenotype and treatment outcome, there is an urgent need to develop precision medicine and personalize dietary supplementation based on an individual’s microbiome.

    • Yu-Jui Yvonne Wan
    •  & Prasant Kumar Jena

  • 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

  • Year in Review |

    HBV and HCV infections continue to be major global health problems, causing over 1 million deaths annually. Key studies this year investigated the innate and adaptive immune responses in different clinical scenarios in HBV infection, whereas others evaluated the merits of transplanting HCV-infected organs into uninfected recipients.

    • Jordan J. Feld
    •  & Adam J. Gehring

  • 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

  • Year in Review |

    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.

    • Ramy Younes
    •  & Elisabetta Bugianesi

  • 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 |

    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
    •  & Henning Grønbæk

  • 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
    •  & Jesus M. Banales

  • Comment |

    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.

    • Naichaya Chamroonkul
    •  & Meena B. Bansal

  • 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

  • News & Views |

    New findings show that a gut microbiome signature derived from metagenomic and phenomic data can accurately predict nonalcoholic fatty liver disease (NAFLD) in obese women. The data highlight a role for phenylacetic acid, a microbial product of aromatic amino acid metabolism, in the cross-talk between the gut microbiome and the host hepatic phenotype.

    • Cyrielle Caussy
    •  & Rohit Loomba

  • 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
    •  & Siew C. Ng

  • 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 |

    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

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