
Theme Issue: Inheritance and Innovation in Traditional Chinese Medicine Treatment of Liver Fibrosis
Executive Chief Editor: XU Chunjun
Chronic hepatitis B-associated liver fibrosis is the key pathological stage in disease progression to liver cirrhosis and even hepatocellular carcinoma. Although antiviral therapy can effectively inhibit HBV replication, reversal of liver fibrosis remains a significant challenge in contemporary clinical practice, and some patients still face the risk of disease progression. With the distinctive advantages of “multiple targets and holistic regulation”, traditional Chinese medicine (TCM) has gradually formed a comprehensive prevention and treatment strategy integrating traditional theories and modern scientific research evidence. “Weakened body resistance and blood stasis” are the core pathogenesis of liver fibrosis and exist throughout the course of the disease, and therefore, the treatment of this disease should focus on stage-specific differentiation and address both the symptoms and root causes. In recent years, significant progress has been achieved in both clinical and basic research. This article systematically reviews the clinical effect and mechanism of action of classic TCM prescriptions (such as Biejia Decoction Pill, Dahuang Zhechong Pill, and Xiaochaihu Decoction), modern Chinese patent drugs, and core TCM drugs (such as Salvia miltiorrhiza, Astragalus membranaceus, and Bupleurum chinense) in the treatment of liver fibrosis. It also analyzes the current challenges in evidence quality and precise medication and proposes future research directions. It is recommended to enhance the role of TCM in the prevention and treatment of liver diseases by deepening research on the “disease-syndrome-prescription-effect-target” association and conducting high-level clinical trials and real-world studies.
Metabolic associated fatty liver disease (MAFLD) has become one of the most prevalent chronic liver disease worldwide, and its progression to liver fibrosis is a key influencing factor for prognosis and the risk of complications. In recent years, novel drugs, such as selective thyroid hormone receptor-β agonists, glucagon-like peptide-1 receptor agonists, and fibroblast growth factor 21 analogs, have shown preliminary efficacy in the treatment of MAFLD-related liver fibrosis; however, such drugs have limited overall effectiveness, and there is still a lack of ideal therapeutic strategy to address the disease across its different stages. Traditional Chinese medicine (TCM), with its characteristics of multiple targets and systemic regulation, has shown unique advantages in this field. This article systematically reviews the basic and clinical research on the anti-fibrotic mechanisms of compound TCM prescriptions and their active components in recent years, focusing on the key processes including hepatic stellate cell activation, lipid metabolism disorders, oxidative stress, immune inflammation, and gut-liver axis dysfunction. Meanwhile, it is pointed out that there are still certain issues in current research, including ambiguities in the clarification of mechanisms, a lack of standardized evaluation systems, and the need to improve the quality of clinical evidence. Future research should emphasize the standardization and quality control of TCM herbal preparations and integrate emerging technologies, such as omics analysis, organoid models, and real-world data, to advance TCM intervention of MAFLD-related liver fibrosis toward well-defined mechanisms, clear therapeutic pathways, and robust scientific evidence. TCM is expected to play a vital role in the multi-dimensional targeted intervention and stage-specific management of MAFLD-related liver fibrosis, in order to provide new perspectives and comprehensive solutions for the precise treatment of chronic liver diseases.
Primary biliary cholangitis (PBC) is a chronic progressive autoimmune liver disease that often progresses to liver fibrosis and even liver cirrhosis. This article summarizes and reviews the research advances in the combined use of traditional Chinese medicine (TCM) and ursodeoxycholic acid in the treatment of PBC-related liver fibrosis. Various studies have shown that integrated traditional Chinese and Western medicine therapy can improve serum fibrosis markers, noninvasive liver fibrosis scores, and liver stiffness measurement in PBC patients with liver fibrosis, with a relatively good safety profile and a potential to delay or even reverse the progression of PBC-related liver fibrosis. However, current evidence is mainly derived from small-scale or short-term clinical observational studies, and in the future, large-scale high-quality randomized controlled trials and long-term follow-up studies are needed in combination with modern scientific technologies to explore underlying mechanisms, thereby further validating its efficacy and promoting the establishment of an evidence-based precise diagnosis and treatment system based on integrated traditional Chinese and Western medicine therapies. Through in-depth research, TCM is expected to play a more important role in the treatment of PBC-related liver fibrosis.
Hepatic fibrosis is a key intermediate stage in the progression of various chronic liver diseases to liver cirrhosis and liver cancer. Traditional Chinese medicine (TCM) has a good effect in the treatment of hepatic fibrosis, but its mechanism of action remains unclear. This article introduces the pathological mechanisms of hepatic fibrosis, including etiology and pathogenesis based on TCM theory and related mechanisms in Western medicine (such as hepatic stellate cell [HSC] activation, hepatic fibrosis driven by metabolic reprogramming, and key signaling pathways in hepatic fibrosis). On this basis, this article analyzes the core mechanisms of TCM in the treatment of hepatic fibrosis, including inhibiting HSC activation and proliferation, suppressing liver inflammation and modulating immunity, counteracting lipid peroxidation damage, regulating the synthesis and secretion of pro-fibrotic factors, maintaining the metabolic balance of extracellular matrix, regulating key signaling pathways, modulating gut microbiota, and inhibiting sinusoidal capillarization, in order to summarize the mechanism of action of TCM in the treatment of hepatic fibrosis and lay a foundation for better developing TCM-based therapeutics for hepatic fibrosis.
Hepatic fibrosis is the common key pathological link of various chronic liver diseases and can progress to malignant diseases such as liver cirrhosis and hepatocellular carcinoma; however, there is still a lack of effective targeted therapeutic drugs at present. Traditional Chinese medicine (TCM) has a marked clinical effect in the prevention and treatment of hepatic fibrosis, yet its precise clinical application and global promotion are greatly limited by the complex components of compound prescriptions and unclear mechanism of action. In recent years, multimodal high-throughput omics technology has achieved rapid development, providing strong technical support for elaborating on the scientific connotation of TCM in the treatment of complex diseases due to its advantages of systematic profiling, big-data analytics, and precise target prediction. In particular, integrated transcriptomic, proteomic, and metabolomic strategies comprehensively elucidate key signaling networks, cellular phenotypic transitions, and extracellular matrix metabolic homeostasis modulated by TCM compounds and monomers and assist in the screening and assessment of effective component groups and novel biomarkers. This article systematically reviews the advances in basic research on TCM prevention and treatment of hepatic fibrosis based on multi-omics technologies in the past five years, summarizes the “drug-target-pathway-phenotype” regulatory network, and elaborates on the core mechanisms of TCM in regulating hepatic stellate cell activation and reversing hepatic fibrosis. Future studies should further delve into the interdisciplinary integration and dynamic analytical methodologies of multi-omics technologies, precisely identify the core regulatory target networks modulated by TCM, and systematically unravel the scientific connotation of compatibility rule in compound prescriptions, in order to provide a theoretical basis for developing efficient targeted drugs for hepatic fibrosis and individualized diagnosis and treatment strategies.
Hepatitis B core antibody (anti-HBc) is an important marker of prior HBV exposure and potential viral persistence. During acute HBV infection, anti-HBc IgM is the earliest antibody to appear shortly after HBsAg, usually lasting for 6 — 12 months, followed by anti-HBc IgG. In patients with chronic infection experiencing acute hepatitis flares, anti-HBc IgM may reappear, though typically at lower titers than in acute infection. “Isolated anti-HBc positivity” may indicate resolved/functional cure of prior HBV infection or occult HBV infection, and there is still a risk of HBV reactivation or transmission during chemotherapy, immunotherapy, blood transfusion, or organ transplantation. Therefore, accurate recognition of the clinical significance of anti-HBc is essential for comprehensive evaluation and individualized management of HBV infection.
Metabolic dysfunction-associated steatotic liver disease (MASLD) poses significant threats to patients with diabetes, but there is still a lack of adequate understanding. About two-thirds of the patients with type 2 diabetes are comorbid with MASLD, which significantly increases the risk of liver cirrhosis, liver cancer, and liver-related mortality and is closely associated with the progression of cardiovascular diseases, extrahepatic malignancies, and diabetes. However, the screening and management of MASLD are not taken seriously in the diagnosis and treatment of diabetes. This consensus report highlights the need for liver fibrosis screening and risk stratification in patients with prediabetes and type 2 diabetes, especially those with obesity, covering the following aspects: the pathophysiological rationale for updated MASLD terminology, the strategies for risk stratification, current treatment regimens (lifestyle interventions and pharmacotherapy), long-term monitoring protocols, and the importance of multidisciplinary collaboration. In addition, it discusses the impact of alcohol consumption on liver health. By enhancing the awareness of MASLD among clinicians and patients and incorporating liver fibrosis screening into standard diabetes management, it is expected to improve the long-term prognosis of patients and reduce the incidence rate of liver cirrhosis.
In 2025, the European Liver and Intestine Transplant Association released the guidelines on the utilization and evaluation of deceased donor livers. The guidelines focus on the definition of high-risk donor livers and the strategies and criteria for dynamic liver assessment, aiming to provide standardized guidance for clinicians. This article gives an excerpt of the key recommendations in the guidelines.
There is still a lack of guidelines on biliary cannulation in recent years. The guidelines are an initiative of the World Endoscopy Organization (WEO) formulated by a panel of experts from Asia, Europe, and America. Through a systematic literature review and the application of the Grading of Recommendations Assessment, Development, and Evaluation methodology, the guidelines address clinical questions pertaining to four key domains, i.e., prevention of post-ERCP pancreatitis (PEP), bile duct cannulation techniques, sphincterotomy/papillary balloon dilation, and bile duct cannulation under special circumstances. Successful biliary cannulation and sphincterotomy are cornerstones of ERCP and are indispensable for almost all therapeutic and advanced diagnostic procedures; however, adverse events, especially PEP, may occur frequently and affect the prognosis of patients. A high success rate of bile duct cannulation and a low incidence rate of PEP are quality indicators for ERCP and should be the goal of all endoscopists. The guidelines aim to provide clinical practice recommendations applicable worldwide, regardless of resources and expertise. The guidelines cover the preoperative, intraoperative, and postoperative management of ERCP, including the measures to reduce the risk of PEP, the technique for an initial biliary cannulation attempt, options for cannulation in case of difficult biliary access, alternatives to ERCP in case of failure (under the guidance of percutaneous and endoscopic ultrasound), and biliary access in altered anatomy (periampullary diverticulum and postsurgical anatomy) and in the presence of duodenal stenosis.
In the traditional theoretical system of traditional Chinese medicine, latent pathogenic factors deeply hiding in the liver and gallbladder of the Jueyin meridian are the core pathogenesis of chronic hepatitis B. Interferon can regulate immunity and eliminate viruses, and clinical cure can be achieved by penetrating and removing pathogenic factors and toxins. However, it often causes dizziness and confusion reactions in the initial stage of treatment, and long-term use can damage Qi-blood; furthermore, its therapeutic effect depends on the patient’s own vital Qi. When traditional Chinese medicine is used in combination with interferon, drug compatibility should be adjusted according to the dynamic changes of pathogenesis, which can reduce adverse reactions, enhance the therapeutic outcome, expand the applicable population of interferon, and improve the clinical symptoms of patients.
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common chronic liver disease in clinical practice, and macrophages are directly involved in the development, progression, and prognosis of MAFLD. Studies have confirmed that glucose metabolic reprogramming in macrophages directly affects immune function, which in turn affects the local inflammatory environment of liver and hepatocyte metabolism. This article reviews the changes in glucose metabolism of macrophages and the corresponding key molecules in the pathogenesis of MAFLD, in order to provide new targets and strategies for the prevention and treatment of MAFLD in the future.
Metabolic dysfunction-associated fatty liver disease (MAFLD) has a relatively high prevalence rate around the world and is closely associated with the development of various extrahepatic malignancies, among which pancreatic cancer exhibits the highest mortality rate. However, the underlying mechanism between MAFLD and pancreatic cancer remains unclear. This article systematically introduces the latest epidemiological evidence of the association between MAFLD and pancreatic cancer, reviews the research advances in pathogenesis, and evaluates the impact of MAFLD severity and high-risk factors (such as nonalcoholic fatty pancreatic disease and intraductal papillary mucinous neoplasm) on the risk of pancreatic cancer. This article points out that insulin resistance, adipokines, and gut dysbiosis may be the key mechanisms of MAFLD promoting the onset of pancreatic cancer, and it also highlights the presence of heterogeneity in current studies. Large-scale prospective cohort studies are needed in the future to further validate the causal relationship and explore more effective strategies for risk stratification.
Hepatic fibrosis is a chronic pathological condition characterized by hepatic stellate cell activation and excessive deposition of extracellular matrix, which would progress to liver cirrhosis and even hepatocellular carcinoma. Therefore, reversal of hepatic fibrosis is of great importance for improving quality of life and prolonging survival time. Currently, various therapeutic drugs for hepatic fibrosis have entered the stage of clinical trial. This article reviews the research advances in therapeutic drugs for hepatic fibrosis in the recent years, in order to provide insights into the treatment of hepatic fibrosis and future research directions for drugs.
Liver cirrhosis is a common chronic progressive liver disease, and such patients often have coagulation disorders, which may lead to thrombotic and hemorrhagic events. While traditional anticoagulant therapies have various limitations, the emergence of novel oral anticoagulants (NOAC) provides new options for anticoagulation treatment in patients with liver cirrhosis. This article comprehensively reviews the application of NOAC in patients with liver cirrhosis, discusses their advantages and potential risks, analyzes their pharmacokinetic and pharmacodynamic characteristics, and evaluates their efficacy and safety in the prevention and treatment of cirrhosis-associated thrombosis based on clinical evidence, in order to provide a reference for clinical decision-making.
Primary liver cancer is a malignant tumor with continuously rising incidence and mortality rates worldwide, imposing a heavy burden on patients and society, and hepatocellular carcinoma (HCC) is a common type of primary liver cancer. As one of the important treatment methods for HCC, radiotherapy can effectively control the local growth of tumors and alleviate symptoms in patients. However, radiotherapy resistance seriously affects the treatment effect and has become a major challenge in clinical treatment. Current research shows a complex mechanism of radiotherapy resistance in HCC, involving multiple factors such as abnormal activation of intracellular signaling pathways, changes in tumor microenvironment, and regulation of gene expression. Therefore, a series of strategies have been proposed to address radiotherapy resistance in clinical practice, including regulating cell signaling pathways, improving tumor microenvironment, and combining different treatment modalities, and such strategies have shown promising application prospects. This article reviews the research advances in the mechanism of radiotherapy resistance and related coping strategies, in order to provide new perspectives for future research on radiotherapy for HCC.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high incidence and mortality rates worldwide, which brings a huge burden to the physical and mental health and socio-economic life of patients. The adenosine monophosphate-activated protein kinase (AMPK) signaling pathway serves as the regulatory center of cellular energy metabolism and is closely associated with the biological activities of HCC cells, including autophagy, apoptosis, and angiogenesis, and it has become a hot topic in current cancer research. Traditional Chinese medicine drugs are abundant in natural components such as flavonoids, alkaloids, and phenols and have the characteristics of multiple targets, pathways, components, and hierarchies. By targeting the AMPK signaling pathway, these components can be used alone or in combination with conventional antitumor therapies to exert an anti-tumor effect on HCC from various aspects. This article reviews and summarizes the extracts of traditional Chinese medicine that target the AMPK signaling pathway for the prevention and treatment of HCC, in order to provide a theoretical basis and a reference for the clinical application of traditional Chinese medicine in the treatment of HCC and the development of related drugs.
Insufficient future liver remnant volume remains a critical limitation for single-stage resection in patients with hepatic malignancies. The techniques for promoting future liver remnant hypertrophy to realize two-stage hepatectomy include portal vein embolization, associating liver partition and portal vein ligation for staged hepatectomy, and portal vein ligation. In recent years, the application of auxiliary liver transplantation has further facilitated two-stage total hepatectomy. This article systematically reviews the clinical applications of these techniques and analyzes their advantages and limitations, so as to provide a reference for optimizing clinical decision-making.
Astragaloside Ⅳ (AS-Ⅳ) is a natural triterpenoid saponin compound derived from Astragalus membranaceus and has shown significant potential in the regulation of liver diseases. This article reviews the latest research advances in AS-Ⅳ in the field of liver diseases in China and globally, and it is found that AS-Ⅳ exerts a liver-protecting effect by regulating lipid metabolism, exerting an anti-tumor/anti-inflammatory/anti-fibrotic effect, and modulating gut microbiota. Its mechanism of action involves multiple signaling pathways, such as AMPK, NLRP3, NF-κB, JAK2/STAT3, and Nrf2. These research findings provide a scientific basis for the development of liver-protecting drugs or functional foods based on the natural product AS-Ⅳ.
Liver diseases are a group of complex clinical conditions caused by various factors and can lead to hepatocyte damage and liver dysfunction, posing a serious threat to human health. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway plays a key regulatory role in the course of liver diseases and is involved in the development, progression, and treatment of various diseases such as viral hepatitis, nonalcoholic fatty liver disease, liver fibrosis, and liver cancer. This article reviews the regulatory mechanisms of the cGAS-STING signaling pathway in processes such as inflammation, autophagy, antiviral response, and oxidative stress, analyzes its molecular function in liver diseases, and explores its application prospect as a potential target for the treatment of liver diseases, in order to provide a theoretical basis for developing novel therapeutic strategies for liver diseases.
As a type of endogenous small non-coding RNA, microRNA (miRNA) can regulate gene expression and thereby intervene against the development and progression of cardiovascular diseases, neurodegenerative diseases, metabolic diseases, and autoimmune diseases. The pathogenesis of cholestasis is complex and is mainly associated with the metabolism and transport of bile acids, oxidative stress, inflammatory response, and intestinal flora. Currently, ursodeoxycholic acid is the preferred drug for the clinical treatment of cholestasis, but it may cause adverse reactions and exhibit poor efficacy in some patients. Studies have shown that miRNA can intervene in the disease process of cholestasis through multiple mechanisms such as regulating bile acid metabolism and transport, alleviating oxidative stress, inhibiting inflammatory response, improving cholangiocyte proliferation, and regulating intestinal flora. It can be used as a new biomarker and action target for cholestasis, with high research potential and value. Therefore, this article summarizes the role and mechanisms of miRNA in regulating cholestasis in recent years, in order to provide a reference for further research on the prevention and treatment of cholestasis by targeting miRNA.
Gallstone disease is a common disease of the biliary system, which is jointly affected by environmental and genetic factors. With the change in dietary patterns, there has been a continuous increase in the the proportion of patients with cholesterol gallstones (CGS), which is a common type of gallstone disease. Studies have shown that genetic factors play a crucial role in the formation of CGS. The formation of CGS mainly depends on two key links of the supersaturation of cholesterol in bile and the presence of mucin that promotes the nucleation of cholesterol crystals. These two processes involve the regulation of multiple proteins. Variations in certain genes can affect the efficiency of cholesterol transport and even change the rate of crystallization and nucleation, thereby influencing the formation of gallstones. This article mainly discusses the key genes associated with cholesterol transport and crystal nucleation, as well as the impact of their mutations on the formation of CGS, in order to gain a deeper understanding of the genetic mechanism of CGS and provide new targets for future clinical treatment.
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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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