Theme Issue: Optimal Management of Acute-on-Chronic Liver Failure Throughout the Whole Disease Course: From Traditional Medicine to Contemporary Technology
Executive Chief Editors: WANG Xianbo
Acute-on-chronic liver failure (ACLF) is a complex clinical syndrome characterized by acute deterioration of liver function caused by different factors on the basis of chronic liver disease, accompanied by liver failure and/or extrahepatic organ failure, and it often has a high short-term mortality rate. With the increasing evidence of evidence-based medicine, multiple guidelines and consensus statements have been released, such as Guidelines for clinical diagnosis and treatment of acute-on-chronic liver failure in traditional Chinese medicine, Expert consensus on the diagnosis and treatment of acute-on-chronic liver failure with integrated traditional Chinese and Western medicine, and Guidelines for the integrated traditional Chinese and Western medicine diagnosis and treatment of acute-on-chronic liver failure, and integrated traditional Chinese and Western medicine therapies for ACLF have been constantly standardized and perfected. This article explores the characteristics and advantages of integrated traditional Chinese and Western medicine therapy in the whole-course management of ACLF from the aspects of early warning and prevention, treatment in the acute stage, management of complications, and rehabilitation care, in order to enhance the understanding of traditional Chinese and Western medicine treatment strategies among clinicians.
Acute-on-chronic liver failure (ACLF) is an acute and critical illness with a high short-term mortality rate, and current therapies mainly focus on elimination of causes, organ support, and prevention of complications. Although liver transplantation is the most effective treatment modality, its clinical application is limited, and traditional Chinese medicine has shown significant advantages and characteristics in the treatment of ACLF. In traditional Chinese medicine, ACLF is classified into the same category as diseases such as “jaundice”, and unlike traditional jaundice which is mostly characterized by excess and heat syndromes, the syndrome of ACLF has gradually transformed from Yang jaundice to Yin jaundice due to the changing disease spectrum of ACLF. With reference to the pathogenesis of ACLF in Western medicine and traditional Chinese medicine theories, this article discusses the essential pathogenesis of ACLF in traditional Chinese medicine, explores the evolution of ACLF syndromes, and reviews the research advances in the clinical efficacy and mechanisms of traditional Chinese medicine based on the three-factor differentiation-based treatment of damp-heat, blood stasis-heat, and spleen deficiency, as well as the safety of spleen-strengthening and Yang-warming drugs in the clinical treatment of ACLF, in order to provide ideas, methods, and evidence for the application of traditional Chinese medicine in ACLF.
Liver failure is a critical illness with a high fatality rate, and its treatment still faces great challenges. This article systematically reviews the achievements of inheritance and innovation in the field of traditional Chinese medicine (TCM) treatment of liver failure in China for the past 60 years. As for clinical research, it was found in the early exploration stage that Yinchenhao decoction combined with Western medicine treatment had a marked therapeutic effect, and enema therapy had shown a certain therapeutic effect, laying a foundation for subsequent research. In the era of evidence-based medicine, the TCM pathogenesis theories were established based on the understanding of “deficiency in origin and excess in superficiality” in liver failure, such as “jaundice due to spleen deficiency and invasion of pathogenic factors”, “Qi-deficiency and blood-stasis jaundice”, and “jaundice due to spleen-kidney Yang deficiency”. Based on the dynamic evolution of TCM syndromes, it is found that HBV-related acute-on-chronic liver failure presents the characteristics of “early excess and late deficiency”, and a framework of staged syndrome differentiation-based treatment has been established as removing excess in the early stage (detoxicating and resolving stasis) and tonifying deficiency in the late stage (warming Yang and securing collapse). As for technological innovation, artificial liver combined with TCM, colonic lavage, and acupuncture and moxibustion has highlighted the advantages of the synergistic effect between multiple targets. Basic research has revealed that Yinchenhao Decoction regulates liver function through the intestinal flora-metabolism axis, the drug combination of Radix Paeoniae Rubra-Radix Aconiti Lateralis Preparata reshapes macrophage polarization, Schisandra chinensis lignans and Schisandra polysaccharides target GSH/GPX4 to modulate lipid homeostasis, and electroacupuncture stimulates ST36 (zusanli) to activate liver regeneration signal, thereby clarifying the molecular mechanism of the treatment principles such as “clearing heat and detoxicating” and “warming Yang and securing collapse”. Current challenges include the heterogeneity of clinical evidence, insufficient association between syndromes and biomarkers, and the bottleneck of cutting-edge technology integration. In the future, it is necessary to establish a two-way closed-loop research paradigm for clinical and basic research, focus on the intestinal microecology-immunity-energy metabolism network, and promote the upgrading of precise TCM treatment.
Acute-on-chronic liver failure (ACLF) is a form of acute hepatic insufficiency that occurs in the context of a chronic liver disease, with a relatively high mortality rate. To improve the prognosis of ACLF patients, it is essential to early identify the patients with pre-ACLF and constantly optimize and innovate treatment regimens for the disease in the progressive stage. With more than 10 years of research, the Chinese CLIF consortium has developed an early warning model for ACLF and established a system for transferring high-risk patients to tertiary hospitals. At present, the real-world study has also confirmed the consistency between the early warning model and actual conditions in clinical practice, making contributions to the early screening, diagnosis, and treatment of ACLF. The treatment options for the progressive stage of ACLF are also expanding, from the development of innovative pharmaceuticals to the use of artificial liver support and stem cell therapy, and such treatment modalities have made significant achievements in clinical studies and are expected to be implemented in the near future. The development of a more efficient diagnostic system and novel treatment modalities has led to a significant improvement in the diagnosis and treatment of ACLF.
Acute-on-chronic liver failure (ACLF) is a complex clinical syndrome, and early identification and accurate prognostic evaluation are of great importance for patient treatment and management. In recent years, with in-depth research on the pathogenesis of ACLF, multiple prognostic biomarkers have been proposed and used in clinical practice. This article systematically reviews the research advances in prognostic biomarkers for ACLF from the aspects of clinical predictive models, immunological biomarkers, metabolic biomarkers, genetic and epigenetic biomarkers, microbiome-related biomarkers, and emerging technologies such as artificial intelligence and multi-omics, and it also discusses the value and application prospects of these biomarkers in the prognostic evaluation of ACLF and proposes future research directions, in order to provide a scientific and comprehensive reference for clinicians, guide individualized treatment and management of ACLF patients, and finally improve the clinical outcomes of patients.
Transjugular intrahepatic portosystemic shunt (TIPS) is currently an effective procedure for the complications of portal hypertension. In recent years, rapid progress has been made in the field of TIPS in terms of technical approaches, prognostic models, and an expanding range of indications. The EASL recently issued the clinical practice guidelines on TIPS to comprehensively address all aspects of TIPS in patients with liver cirrhosis. This article makes an excerpt of the key recommendations in the guidelines.
Since the Asia-Pacific Association for the Study of the Liver (APASL) issued the clinical practice guidelines for metabolic associated fatty liver disease (MAFLD) in 2020, the research on MAFLD has been further deepened. Therefore, APASL has made comprehensive updates and revisions based on the previous guidelines, and the latest version of the clinical practice guidelines for diagnosis and management of MAFLD, which was released in February 2025, has updated the epidemiology, screening, assessment, and treatment of MAFLD, aiming to promote the clinical practice, knowledge popularization, and scientific research of MAFLD. This article makes an excerpt and an interpretation of the updated key points of the guidelines.
Malnutrition is a common complication in patients with liver disease, particularly in the advanced stage of disease, and it significantly affects the prognosis of patients. In 2025, the American College of Gastroenterology released Clinical Guideline: Malnutrition and Nutritional Recommendations in Liver Disease, which covers the definition, causes, nutritional assessment methods, and intervention strategies for malnutrition associated with liver disease, which provides evidence-based recommendations for nutritional management in liver disease. This article makes an excerpt of the recommendations and key concept statements from the guideline.
Epigenetic mechanisms play a crucial role in the development and progression of nonalcoholic fatty liver disease (NAFLD), especially among lean individuals. The research on related epigenetic mechanisms has provided new clues and directions for revealing the underlying causes and treatment strategies of NAFLD. This article introduces the role of epigenetics in the development and progression of NAFLD among lean individuals in recent years, analyzes the latest research advances in the epigenetics of NAFLD in this population, and briefly describes the basic concepts of epigenetics, including DNA methylation, histone modifications, and non-coding RNA regulation. This article also discusses how epigenetic alterations impact the pathogenesis, disease progression, and treatment strategies of NAFLD in lean individuals.
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common chronic liver disease with the pathological feature of lipid accumulation in the liver, and it is closely associated with liver metabolic disorders. The latest research has shown that the pathogenesis of MAFLD is associated with the abnormal expression of specific genes, especially the fat mass and obesity-associated (FTO) gene. The abnormal activity of the FTO gene may lead to an imbalance in liver lipid metabolism, which manifests as the increase in fatty acid synthesis and the reduction in fatty acid oxidation, thereby promoting liver fat deposition and inflammatory response. Therefore, regulating the expression or activity of the FTO gene is considered one of the potential strategies for the treatment of MAFLD. At present, drug research targeting the function of the FTO gene has achieved preliminary results, and inhibition of the activity of the FTO gene can help to regulate liver lipid metabolism and alleviate liver inflammatory injury. This article reviews the mechanism of action of the FTO gene in the development and progression of MAFLD, summarizes the advances in drug research on the FTO gene and related metabolic pathways in recent years, and analyzes their application prospect in research and treatment.
Metabolic associated fatty liver disease (MAFLD) is a liver disease associated with metabolic disorders, and it is characterized by excessive fat deposition in hepatocytes and is closely associated with insulin resistance and genetic susceptibility. Aging is an important factor in the progression of MAFLD and is positively correlated with the mortality rate of patients with MAFLD. The pathophysiological mechanisms of MAFLD involve lipid metabolism disorders, insulin resistance, inflammation, and oxidative stress, and aging exacerbates the pathological process of MAFLD by further affecting these key mechanisms. Cell senescence is an important factor in organismal aging, and therapeutic strategies targeting senescent cells can reduce the number of senescent cells or inhibit the inflammatory factors secreted by such cells, thereby helping to slow down the progression of MAFLD. In addition, the screening of novel regulatory factors provides new targets for the development of new drugs for MAFLD treatment. Although several anti-aging therapies have entered clinical trials, further studies are needed to validate the specificity and potential liver damage of these therapies due to the complex mechanisms of aging on the liver. Transforming multisystem metabolic dysfunction therapies for MAFLD into specialized therapies for aging may provide new ideas for MAFLD drug development.
Primary biliary cholangitis (PBC) and Sjögren’s syndrome (SS) are both autoimmune disorders characterized by the involvement of epithelial tissue, and comorbidity of PBC and SS is often observed in clinical practice, suggesting that these two diseases may have common pathogeneses. Currently, there are still no specific targeted therapies for PBC and SS, and the therapeutic approach for systemic manifestations mainly relies on the treatment regimens for other autoimmune disorders. This article reviews the various potential therapeutic targets that have been clarified in the pathogenesis of PBC and SS and points out that targeted therapies for these two diseases can be developed based on the common immunopathological mechanism of PBC and SS, thereby providing valuable ideas for developing novel therapies.
As a key member of the insulin-like growth factor family, insulin-like growth factor-Ⅰ (IGF-Ⅰ) is mainly synthesized in the liver and is widely distributed in the human body, and it is involved in the physiological processes such as cell proliferation, differentiation, metabolism, and apoptosis. Studies have shown that the level of IGF-Ⅰ is negatively correlated with the severity of liver cirrhosis, and IGF-Ⅰ mainly affects the progression of liver cirrhosis by inhibiting liver fibrosis, promoting DNA damage repair, and regulating lipid metabolism. Monitoring of IGF-Ⅰ level is expected to provide an evaluation indicator for improving the prognosis of patients with liver cirrhosis, and stimulating the action pathway of IGF-Ⅰ or regulating its expression level may become a new method for the treatment of liver cirrhosis. This article reviews the research advances in IGF-Ⅰ in liver cirrhosis, in order to provide new ideas for the diagnosis and treatment of liver cirrhosis.
Hepatocellular carcinoma is one of the most common cancers, and due to the lack of obvious specific symptoms in its early stage, patients are often in the advanced stage at the time of diagnosis and tend to have a poor prognosis. Timely diagnosis and effective treatment in the early stage can help to prolong the survival time of patients. Liquid biopsy is a noninvasive technique that can obtain the information of tumor by detecting and analyzing related biomarkers, including circulating tumor cells, circulating tumor DNA, and extracellular vesicles, thereby contributing to early diagnosis, molecular pathological typing, and prognosis prediction. This article reviews the research advances in the application of liquid biopsy in the diagnosis and treatment of hepatocellular carcinoma.
Liver cancer has high prevalence and mortality rates around the world, and its development and progression are closely associated with the interaction between the tumor microenvironment and tumor-associated macrophages (TAMs). TAMs play a significant role in immune suppression, immune escape, cell proliferation, invasion, metastasis, and drug resistance in liver cancer. Traditional Chinese medicine (TCM), with its unique therapeutic concepts and methods, has shown great potential in regulating TAMs and improving the prognosis of liver cancer. This article reviews the role and molecular mechanisms of TCM in regulating TAMs for the treatment of liver cancer, discusses the key role of TAMs in the progression of liver cancer, and analyzes the impact of Chinese medicinal components on the recruitment, polarization, and activity of TAMs and the expression of related factors based on TCM theory. Studies have shown that TCM can regulate the polarization state of TAMs, promote the formation of M1-type antitumor macrophages, and inhibit the activity of M2-type tumor macrophages, thereby playing a role in inhibiting the proliferation of liver cancer cells, promoting apoptosis, inhibiting angiogenesis, and enhancing immune response. In addition, this article also summarizes the molecular targets and mechanisms of action of TCM monomers, compound prescriptions, and novel preparations in the treatment of liver cancer, such as inhibiting the secretion of cytokines by TAMs, regulating signaling pathways, and affecting metabolic pathways, in order to provide a scientific basis for the application of TCM in liver cancer treatment and offer new ideas for immunotherapy for liver cancer.
With the concurrent development of traditional Chinese medicine (TCM) and metabolomics in the diagnosis and treatment of liver failure, techniques such as nuclear magnetic resonance, mass spectrometry, chromatography, metabolic flux analysis, and bioinformatics enable the qualitative or quantitative analysis of endogenous small molecule metabolites in animal models of liver failure and patients with liver failure. These methods help identify specific biomarkers for early diagnosis and clinical intervention. This article reviews recent advancements in metabolomics for the early diagnosis of liver failure, biomarker discovery, identification of TCM syndromes, and the application of TCM in treating liver failure, aiming to provide a basis for TCM-based diagnosis and treatment of liver failure.
Liver failure (LF) is a severe clinical syndrome characterized by severe impairment or decompensation of liver function. At present, the key role of immune molecules in the pathogenesis of LF has been well established. These molecules not only directly participate in the pathological process of LF, but also influence the course of LF by modulating the behavior of immune cells. In addition, immune molecules can be used as potential biomarkers for evaluating the prognosis of LF. This article summarizes the role of immune molecules in LF and explores the therapeutic strategies based on these immune molecules, in order to provide new directions for the diagnosis and treatment of LF.
The immunomodulatory, repair, and regeneration-promoting functions of mesenchymal stem cells make them one of the potential treatment methods for liver diseases. At present, viral and non-viral delivery methods have been developed to genetically modify mesenchymal stem cells, and gene modification can promote the survival, homing, and cytokine secretion of mesenchymal stem cells, thereby enhancing the ability of mesenchymal stem cells to treat liver diseases. This article mainly summarizes the research advances in gene-modified mesenchymal stem cells in the treatment of liver diseases, in order to provide new insights and strategies for the clinical treatment of liver diseases.
Liver diseases cannot be easily detected in the early stage, and although invasive diagnostic methods, such as liver biopsy, are relatively accurate, they tend to have a low degree of acceptance, which greatly limits the improvement in diagnosis and treatment techniques for liver diseases. Therefore, it is of great importance to search for new biomarkers and therapeutic targets. As an emerging biomarker for liquid biopsy, tRNA-derived small RNA (tsRNA) is abnormally expressed in various liver diseases including viral hepatitis, fatty liver disease, liver injury, and liver cancer, and it can affect the development and progression of liver diseases by regulating the biological functions such as gene expression, epigenetic regulation, and protein translation. This article reviews the origin, classification, and biological function of tsRNA, as well as the research advances in tsRNA as biomarkers and potential therapeutic targets for liver diseases, so as to provide ideas for the early diagnosis and treatment of liver diseases.
Biliary atresia (BA) is characterized by progressive inflammation and fibrous obstruction of bile ducts, ultimately leading to cholestatic liver cirrhosis. Kasai surgery is the standard procedure for the treatment of BA, and early diagnosis is a key influencing factor for the prognosis of BA. Indocyanine green (ICG) is a near-infrared photosensitive dye that is efficiently and selectively absorbed by hepatocytes after intravenous injection, and it enters the intestine via bile and is excreted with the feces in the free form, with a favorable safety profile. In addition, ICG can emit fluorescence under near-infrared light, which can be captured by camera instruments and converted into visual images, and ICG fluorescence imaging technology can reflect the intraoperative situation in real time and significantly improve the success rate of the surgical procedure. This article reviews the advances in the application of ICG in early preoperative diagnosis, intraoperative imaging, and postoperative liver function assessment in recent years.
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- 1Current situation in the research of Gilbert’s syndrome
- 2Review of acute pancreatitis scoring systems
- 3Clinical value of 13C-methacetin breath test for assessing liver function in patients with cirrhosis
- 4Studies on relevant gactors of Child-Pugh grading in hepatic cirrhosis
- 5Meta-analysis of 111 patients with nonalcoholic steatohepatitis-associated hepatocellular carcinoma
- 6Research state and prospect of hyponatremia in cirrhosis
- 7Relationship between Epstein-Barr virus infection and hepatic lesions in children
- 8Congenital bile acid synthesis defect and cholestatic liver disease
- 9Interventional treatment for Budd-Chiari syndrome:reports of 883 cases
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- 1The guideline of prevention and treatment for chronic hepatitis B: a 2015 update
- 2Chinese guidelines for the management of acute pancreatitis ( Shenyang , 2019 )
- 3The guideline of prevention and treatment for chronic hepatitis B(2010 version)
- 4Comprehensive guidelines for the diagnosis and treatment of pancreatic cancer (2018 version)
- 5Consensus on the diagnosis and management of primary biliary cirrhosis (cholangitis)(2015)
- 6Diagnosis, management, and treatment of hepatocellular carcinoma (V2017)
- 7Consensus on the diagnosis and management of autoimmune hepatitis(2015)
- 8Current situation in the research of Gilbert’s syndrome
- 9Guidelines for the prevention and treatment of chronic hepatitis B (version 2019)
- 10
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