Featured
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In Brief |
Sintilimab as adjuvant therapy for patients with resected HCC at high risk of recurrence
- Jordan Hindson
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Review Article |
Friend or foe? The elusive role of hepatic stellate cells in liver cancer
Hepatic stellate cells (HSCs) drive liver fibrosis and are closely linked to liver cancer development. This comprehensive Review provides an in-depth analysis of the specific characteristics of HSCs in cancer, highlighting therapeutic implications based on progress in clarifying HSC biology.
- Bruno Cogliati
- , Chittampalli N. Yashaswini
- & Scott L. Friedman
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Review Article |
Hepatocellular carcinoma surveillance — utilization, barriers and the impact of changing aetiology
In this Review, Huang et al. discuss the current status of hepatocellular carcinoma surveillance, the remaining challenges, including the changing aetiology of liver disease, and strategies to improve the utilization and quality of surveillance.
- Daniel Q. Huang
- , Amit G. Singal
- & Rohit Loomba
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Review Article |
Nonalcoholic steatohepatitis-related hepatocellular carcinoma: pathogenesis and treatment
In this Review, Llovet and colleagues discuss advances in our knowledge of the pathogenesis and clinical management of nonalcoholic steatohepatitis-related hepatocellular carcinoma. They also discuss future prospects and unmet needs.
- Josep M. Llovet
- , Catherine E. Willoughby
- & Scott L. Friedman
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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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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 |
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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Review Article |
Circulating biomarkers in the diagnosis and management of hepatocellular carcinoma
Surveillance of hepatocellular carcinoma (HCC), one of the most lethal solid cancers globally, is insensitive for the detection of early-stage tumours. In this Review, the authors discuss HCC biomarkers that can improve early diagnosis, therapy monitoring and prediction of therapy response.
- Philip Johnson
- , Qing Zhou
- & Y. M. Dennis Lo
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Roadmap |
A framework for fibrolamellar carcinoma research and clinical trials
In this Roadmap, Furth, Sethupathy and colleagues discuss advances in our understanding of the mechanisms and treatments of fibrolamellar carcinoma, a rare hepatic cancer that primarily occurs in adolescents and young adults. Recommendations for future progress in research and clinical trials are proposed.
- Timothy A. Dinh
- , Alan F. Utria
- & Praveen Sethupathy
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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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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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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 |
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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Review Article |
Exploring liver cancer biology through functional genetic screens
This Review describes how functional genetic screens can shed light on various outstanding questions in liver cancer biology, including which genes can drive hepatocarcinogenesis, how to improve the efficacy of existing therapies and how to find novel therapeutic targets for liver cancer.
- Cun Wang
- , Ying Cao
- & Wenxin Qin
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Review Article |
Advances in immunotherapy for hepatocellular carcinoma
Immunotherapeutic interventions might be effective tools for the treatment of hepatocellular carcinoma. This Review provides up-to-date information on the clinical use of currently available immunotherapies in hepatocellular carcinoma, the mechanisms of response and resistance, and the therapeutic strategies under development.
- Bruno Sangro
- , Pablo Sarobe
- & Ignacio Melero
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Review Article |
The role of farnesoid X receptor in metabolic diseases, and gastrointestinal and liver cancer
Farnesoid X receptor (FXR) is involved in the control of bile acid synthesis and enterohepatic circulation. This Review discusses the role of FXR in metabolic diseases and gastrointestinal and liver cancers, highlighting underlying mechanisms and potential therapeutic targets.
- Lulu Sun
- , Jie Cai
- & Frank J. Gonzalez
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Review Article |
Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma
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
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Year in Review |
Pursuing efficacious systemic therapy for hepatocellular carcinoma
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
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Review Article |
Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention
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
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Review Article |
Maladaptive regeneration — the reawakening of developmental pathways in NASH and fibrosis
Emerging data have revealed that nonalcoholic steatohepatitis (NASH) and fibrosis are associated with the reactivation of developmental pathways in the liver injury response. This Review describes the role of these pathways in liver development and in the pathogenesis of NASH and fibrosis.
- Changyu Zhu
- , Ira Tabas
- & Utpal B. Pajvani
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Review Article |
Modern therapeutic approaches for the treatment of malignant liver tumours
Modern therapies for malignant liver tumours integrate neoadjuvant and adjuvant strategies. This broad Review discusses these approaches, including advances in staged surgeries, systemic therapies, ablation therapies and liver transplantation.
- Henrik Petrowsky
- , Ralph Fritsch
- & Pierre-Alain Clavien
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News & Views |
Therapy-induced senescence — an induced synthetic lethality in liver cancer?
Cancer therapies, in addition to inducing cell death, can trigger cellular senescence of tumour cells, and factors secreted from senescent cells might negatively affect the tumour microenvironment. A new study by Wang et al. shows that eradication of therapy-induced senescent cells (senolysis) can improve the outcome of liver cancer therapy.
- Katharina Wolter
- & Lars Zender
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Review Article |
Harnessing big ‘omics’ data and AI for drug discovery in hepatocellular carcinoma
Several big data ‘omics’ studies have analysed hepatocellular carcinoma (HCC). This Review describes omics studies in HCC and their potential in drug discovery and as candidate biomarkers. The application of emerging new artificial intelligence methods in HCC drug discovery is also discussed.
- Bin Chen
- , Lana Garmire
- & Xin Chen
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Review Article |
Tumour evolution in hepatocellular carcinoma
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
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Year in Review |
What’s new in NAFLD pathogenesis, biomarkers and treatment?
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
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Year in Review |
Joining the dots for better liver cancer treatment
In 2019, powerful single-cell analyses were applied to liver cancer biology at an unprecedented level. In parallel with this achievement was the identification of serum α-fetoprotein as a biomarker for patient selection in the use of ramucirumab for liver cancer and that β-catenin activation can distinguish between liver cancer immunotherapy responders and non-responders.
- Lo-Kong Chan
- & Irene Oi-Lin Ng
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Review Article |
Metabolic rearrangements in primary liver cancers: cause and consequences
Primary liver cancers are frequently accompanied by rearrangements of metabolic pathways. This Review discusses the role of metabolic liver disruptions and the implications of these processes, emphasizing their clinical relevance and value in early diagnosis and prognosis and as putative therapeutic targets.
- Letizia Satriano
- , Monika Lewinska
- & Jesper B. Andersen
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Review Article |
A global view of hepatocellular carcinoma: trends, risk, prevention and management
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. This Review summarizes the epidemiology, risk factors (including viral hepatitis and NAFLD), molecular profiles and treatment of HCC, providing insights into how the global burden of HCC can be reduced.
- Ju Dong Yang
- , Pierre Hainaut
- & Lewis R. Roberts
Artificial intelligence in liver cancer — new tools for research and patient management
Lactylation and HCC progression
CXCR2 inhibition in NASH-HCC
Glycogen phase separation and liver cancer
E. faecalis promotes liver carcinogenesis
Lenvatinib plus EGFR inhibition for liver cancer
Molecular landscape of NASH-HCC
T cells in NASH and liver cancer: pathology and immunotherapy
Linking gut vascular barrier to CRC liver metastases