Research Highlight |
Featured
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Review Article |
Gene therapy for liver diseases — progress and challenges
In this Review, the authors discuss gene therapy involving the use of recombinant adeno-associated virus vectors for the treatment of inherited liver diseases, including ongoing clinical trials that are producing promising results.
- Nerea Zabaleta
- , Carmen Unzu
- & Gloria Gonzalez-Aseguinolaza
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Year in Review |
Advancing alcohol-related liver disease: from novel biomarkers to refining selection for liver transplantation
In 2022, we witnessed advances in the field of alcohol-related liver disease. Key developments included the discovery of novel proteomics-based biomarkers and potential therapeutic targets that regulate the recognition of molecules derived from gut microbiota to modulate liver injury. Additionally, there have been significant advances in refining selection for liver transplantation in severe alcohol-associated hepatitis.
- Juan Pablo Arab
- & Ramon Bataller
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Year in Review |
NAFLD, MAFLD and obesity: brothers in arms?
2022 was a proficuous year in both the nonalcoholic fatty liver disease (NAFLD) and obesity fields. Pharmacological treatment for obesity and NAFLD is moving forward, with the possibility of replacing bariatric surgery, artificial intelligence might help us access the histological effects of new drugs, and there were advances in personalized hepatocellular carcinoma screening in patients with NAFLD.
- Mariana Verdelho Machado
- & Helena Cortez-Pinto
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Review Article |
Evolving therapeutic landscape of advanced hepatocellular carcinoma
This Review discusses the current and emerging therapeutic landscape for treatment of advanced hepatocellular carcinoma, including molecular-targeted monotherapies, immuno-oncology monotherapies, combination therapies and novel therapeutic approaches.
- Chen Yang
- , Hailin Zhang
- & Cun Wang
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In Brief |
Investigating two versus three doses of mRNA vaccine in patients with cirrhosis
- Jordan Hindson
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Review Article |
Mechanisms of pruritus in cholestasis: understanding and treating the itch
Pruritus in cholestatic liver diseases is a frequent symptom that impairs quality of life. This Review describes the mechanisms underlying cholestasis-associated itch, discusses potential pruritogens, and highlights therapeutic approaches to manage pruritus in various conditions, including primary biliary cholangitis, primary sclerosing cholangitis and intrahepatic cholestasis of pregnancy.
- Ulrich Beuers
- , Frank Wolters
- & Ronald P. J. Oude Elferink
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Review Article |
Global epidemiology of alcohol-associated cirrhosis and HCC: trends, projections and risk factors
Global alcohol consumption has increased in the past two decades and is projected to increase further. In this Review, Loomba and colleagues discuss the global epidemiology of alcohol-associated cirrhosis and hepatocellular carcinoma, including risk factors, trends and projections.
- Daniel Q. Huang
- , Philippe Mathurin
- & Rohit Loomba
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Review Article |
Gut immune cell trafficking: inter-organ communication and immune-mediated inflammation
Intestinal immune cell trafficking contributes to the pathogenesis of immune-mediated inflammatory diseases (IMIDs). This Review discusses the underlying immune cell trafficking mechanisms along the gut–liver, gut–joint and gut–brain axes and provides an overview of their implications for treatment options in IMIDs.
- Sebastian Zundler
- , Claudia Günther
- & Markus F. Neurath
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Review Article |
Benign liver tumours: understanding molecular physiology to adapt clinical management
Here, the authors provide an overview of benign liver tumours (hepatic haemangioma, focal nodular hyperplasia and hepatocellular adenoma), including pathogenesis, diagnosis and management. Insights into how molecular physiology could inform clinical practice are also highlighted.
- Jean-Charles Nault
- , Valérie Paradis
- & Jessica Zucman-Rossi
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Comment |
Sudden onset hepatitis in children
The recent increase in unexplained acute hepatitis in children in 2022 has focused attention on acute paediatric liver disease. We discuss emerging evidence and leading causal hypotheses in context with potential long-term effects of the COVID-19 pandemic for young children.
- Deirdre A. Kelly
- & Zania Stamataki
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In Brief |
Proteomics and machine-learning models for alcohol-related liver disease biomarkers
- Jordan Hindson
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Review Article |
Metabolic (dysfunction)-associated fatty liver disease in individuals of normal weight
Metabolic (dysfunction)-associated fatty liver disease (MAFLD) is a chronic liver disease typically associated with obesity. This Review discusses the epidemiology and physiology of individuals of normal weight with MAFLD and provides insights into their metabolic health and metabolic adaptation.
- Mohammed Eslam
- , Hashem B. El-Serag
- & Jacob George
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Comment |
Sex bias in clinical trials in gastroenterology and hepatology
Biological sex bias in clinical trials is a common issue in various medical fields, including gastroenterology and hepatology. Without sex parity and increased attention to sex-specific analyses, the translation of trial results into real-world clinical practice remains suboptimal with unpredictable consequences for patient care.
- Patrizia Burra
- , Alberto Zanetto
- & Giacomo Germani
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News & Views |
Achieving health equity in liver disease pharmacotherapy
New data demonstrate racial and ethnic disparities in access to prescription medications in persons with chronic liver disease in the USA. Here, we discuss potential health equity solutions that address structural and social determinants of health to mitigate liver health inequities in access to liver disease pharmacotherapies.
- Ani Kardashian
- & Lauren D. Nephew
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Review Article |
Genetics, pathobiology and therapeutic opportunities of polycystic liver disease
Polycystic liver diseases are genetic disorders that cause hepatic cystogenesis, which can coincide with cyst development in the kidney, with women being more affected than men. This Review discusses the genetics and underlying mechanisms and provides up-to-date therapeutic insights.
- Paula Olaizola
- , Pedro M. Rodrigues
- & Jesus M. Banales
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Comment |
COVID-19 and liver disease: where are we now?
Patients with end-stage liver disease and COVID-19 are at a higher risk of hospitalization, ventilation and death than those without chronic liver disease. Whether the aetiology of liver disease also affects the natural history of COVID-19 in cirrhosis is debated. Effective and universal vaccination is paramount to combat SARS-CoV-2 infection.
- Francesco Paolo Russo
- , Patrizia Burra
- & Alberto Zanetto
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Review Article |
Hippo signalling in the liver: role in development, regeneration and disease
In this Review, Russell and Camargo summarize the role of the Hippo signalling pathway in liver development, homeostasis, regeneration and disease, and discuss development of potential therapeutics for liver diseases such as fibrosis and cancer.
- Jacquelyn O. Russell
- & Fernando D. Camargo
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World View |
Developing a cadre of clinician trialists in gastroenterology and hepatology
There has been little or no formal training for clinical trial methodology for clinicians. Coupled with the growing complexities of randomized controlled trials, a focus on training is needed to develop the next cadre of clinician trialists.
- Nurulamin M. Noor
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Review Article |
Neutrophils as potential therapeutic targets in hepatocellular carcinoma
Growing evidence indicates that neutrophils are involved in tumorigenesis, progression and metastasis of hepatocellular carcinoma (HCC). Here, Geh and colleagues summarize neutrophil phenotypes in HCC, describe the pathogenetic mechanisms underlying these contributions of neutrophils to HCC and highlight emerging neutrophil-targeted therapies.
- Daniel Geh
- , Jack Leslie
- & Derek A. Mann
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Perspective |
Machine perfusion of the liver: applications in transplantation and beyond
Ceresa et al. discuss machine perfusion technologies for liver preservation and transplantation, including the potential of hypothermic and normothermic machine perfusion to improve preservation time and organ quality, as well as the future applications of perfusion technologies.
- Carlo D. L. Ceresa
- , David Nasralla
- & Peter J. Friend
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Year in Review |
Interrogating mechanisms of liver fibrosis with omics
Important studies in 2021 demonstrated sophisticated developments in the study of liver fibrosis through omics. Cell-specific mapping, single-cell sequencing and deep-learning systems revealed complex intra-hepatic mechanisms and new computational platforms facilitating the research towards drug discovery in liver disease and in fibrosis.
- Fiona Oakley
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News & Views |
Natural history of NAFLD: knowns and unknowns
Although nonalcoholic fatty liver disease is the most prevalent liver disease worldwide, there is a paucity of good-quality data on its natural history and most studies to date have reported on retrospective data. Robust data are required to inform regulatory end points, trial design and models of care.
- Emmanuel A. Tsochatzis
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Year in Review |
Decoding therapy resistance in liver tumours: a giant leap
In 2021, our understanding of resistance to therapy in primary liver tumours improved drastically. By taking a holistic approach, three independent studies have characterized the tumour cell biodiversity across space, time and aetiologies in primary liver cancer, decoding the crosstalk between different cell types within the tumour ecosystem and their individual contributions to therapy resistance.
- Chantal Desdouets
- & Amaia Lujambio
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Review Article |
Management of alcohol use disorder in patients with cirrhosis in the setting of liver transplantation
In this Review, Arab and colleagues discuss management of alcohol use disorder in patients with alcohol-associated liver disease, particularly in the setting of liver transplantation. An integrative, multidisciplinary approach is proposed.
- Juan Pablo Arab
- , Manhal Izzy
- & Vijay H. Shah
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Editorial |
Paving the way: the road to be taken for proper NAFLD health care
A new Consensus Statement calls for national and global action bringing fatty liver disease to the forefront of the public health-care system.
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Consensus Statement |
Advancing the global public health agenda for NAFLD: a consensus statement
Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease with a substantial burden worldwide. In this Consensus Statement, a global multidisciplinary group of experts develop consensus statements and recommendations addressing a broad range of topics on NAFLD to raise awareness and spur action.
- Jeffrey V. Lazarus
- , Henry E. Mark
- & Ming-Hua Zheng
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Review Article |
Cirrhosis-associated immune dysfunction
In this Review, Albillos and colleagues describe cirrhosis-associated immune dysfunction (CAID) and its components — systemic inflammation and immune deficiency — as well as the role of CAID in the pathogenesis of acute-on-chronic liver failure. Therapies that aim to modulate CAID are discussed.
- Agustín Albillos
- , Rosa Martin-Mateos
- & Melchor Álvarez-Mon
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Review Article |
Metabolomics and lipidomics in NAFLD: biomarkers and non-invasive diagnostic tests
Metabolomics and lipidomics approaches are being used to identify biomarkers for nonalcoholic fatty liver disease (NAFLD). This Review discusses the application of metabolomics and lipidomics in clinical studies and in the identification of key metabolic pathway alterations in NAFLD.
- Mojgan Masoodi
- , Amalia Gastaldelli
- & Matej Orešič
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Review Article |
Cancer stem cells in hepatocellular carcinoma — from origin to clinical implications
The complexity of hepatocellular carcinoma (HCC) hinders effective treatment. Here, Lee and colleagues summarize cancer stem cell (CSC) origin and plasticity, CSC–immune system interactions and the effects of the microenvironmental niche on cancer stemness in HCC. Potential CSC-based therapies for HCC are also presented.
- Terence Kin-Wah Lee
- , Xin-Yuan Guan
- & Stephanie Ma
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Research Highlight |
Liver macrophages and neutrophils in immunotherapy-related toxicity
- Jordan Hindson
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News & Views |
Therapeutic base editing in the adult liver
Gene editing to correct inherited liver disorders has promise for future therapeutic intervention, but lack of effective and safe delivery of the gene-editing machinery to hepatocytes complicates its clinical application. Two studies now report efficient delivery to the liver of non-human primates, providing proof of concept for novel treatment of inherited hypercholesterolaemia.
- Coen C. Paulusma
- & Piter J. Bosma
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Review Article |
Dietary carbohydrates and fats in nonalcoholic fatty liver disease
This Review discusses the role of dietary fats and carbohydrates in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Studies on the dietary habits of patients with NAFLD, and the effect on liver fat accumulation of altering dietary macronutrients, are also reviewed.
- Hannele Yki-Järvinen
- , Panu K. Luukkonen
- & J. Bernadette Moore