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Chronic liver disease, a leading cause of death worldwide, is characterized by chronic inflammation and liver fibrosis, which might lead to cirrhosis and, eventually, liver cancer. Diagnosis is usually made at the stage of advanced and irreversible cirrhosis, at which point the patient's survival depends on liver transplantation. An early diagnosis at the reversible stage of fibrosis could stop chronic liver disease progression and enable personalized treatment, reducing morbidity.
This Collection of articles accompanies a special Nature Reviews Gastroenterology & Hepatology Focus issue on liver fibrosis and includes Review, Perspective and Comment articles from researchers and clinicians who are leaders in this field. These articles provide a comprehensive overview of the pathophysiology of liver fibrosis, including the role of inflammation and cellular stress in disease development and the role of hepatic stellate cells in liver tumorigenesis, and discuss current and future therapeutic avenues towards personalized treatment. They also highlight the current status of imaging in liver fibrosis, models of care, and historical research in this field. As there is an urgent need for early diagnosis, this Collection provides an up-to-date resource of the relevant research in the field.
Liver inflammation is a key process that orchestrates intrahepatic injury. This Review offers a comprehensive overview of the inflammatory mechanisms of hepatic fibrosis and discusses current advances and therapeutic implications.
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.
Increasing evidence shows a role of cellular stress responses in nonalcoholic steatohepatitis (NASH) and liver fibrosis pathogenesis. This Review provides a comprehensive overview of the molecular mechanisms involved in cellular stress in fibrogenesis and their role in NASH progression.
Tackling fibrosis in patients with nonalcoholic steatohepatitis (NASH), one of the major causes of liver cirrhosis, is critical in improving patient outcomes. This Perspective discusses potential strategies to develop better antifibrotic therapies in NASH, from the discovery process to future clinical trials.
Liver fibrosis is a substantial risk factor for liver cancer development. In this issue, we focus on molecular and cellular mechanisms of hepatic fibrogenesis and discuss therapeutic implications.
Imaging techniques for assessing liver fibrosis are advancing. This Clinical Outlook article discusses the best practices and reviews emerging options for magnetic resonance and ultrasound-based elastography.
In this Comment, we provide a strategic framework for what could and should be measured, across four domains, to optimize standards of care for multidisciplinary models of care in nonalcoholic fatty liver disease.
A prospective study suggests that the risk of liver fibrosis with methotrexate treatment has been overestimated. The findings suggest the need to reconsider the intensive strategies and the screening tools that are recommended for monitoring liver fibrosis in patients receiving methotrexate.
In this Review, Huang et al. highlight global trends in the epidemiology of cirrhosis, including contributions of various aetiologies of liver disease, and consider what needs to be done to address projected increases in the burden of cirrhosis.
Delineation of fibroblast heterogeneity has the potential to identify select mesenchymal populations involved in health and disease. A recent study integrated single-cell transcriptomic data to generate a fibroblast atlas of steady-state and perturbed tissues in mice and humans, showing baseline and context-specific fibroblast phenotypes between species and pathologies, including IBD.
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.