
Theme Issue: Ultrasound Diagnosis and Treatment of Hepatocellular Carcinoma: Current Status,Challenges and Future Prospects
Executive Chief Editor: Huang Pintong
The Second Affiliated Hospital of Zhejiang University School of Medicine
Hepatocellular carcinoma (HCC) is a highly prevalent malignant tumor in China, and minimally invasive local intervention has become the core curative treatment for early- and intermediate-stage HCC. Leveraging its advantages of noninvasiveness, real-time operation, and bedside accessibility, ultrasound plays a pivotal role throughout the entire clinical pathway of screening for high-risk populations, qualitative diagnosis of focal lesions, ablation guidance, and efficacy monitoring throughout the entire post-treatment course. In this theme issue of Journal of Clinical Hepatology titled “Ultrasound diagnosis and treatment of hepatocellular carcinoma: Current status, challenges, and future prospects”, six leading experts in the field of ultrasound from China have been invited to contribute to a series of expert forums, systematically addressing the research hotspots, current bottlenecks, and translational pathways in this field from six key dimensions of integrated diagnosis and treatment in primary care, early differential diagnosis, intelligent imaging technologies, precision interventional ablation, standardized assessment of ablation efficacy, and bibliometric analysis and emerging techniques of contrast-enhanced ultrasound. With reference to the core viewpoints of the six reviews, this article provides a stratified commentary on the main trajectories of precise and intelligent development in HCC ultrasound, identifies key breakthroughs and unresolved challenges across various directions, and envisions a new landscape of multi-technological integration and collaborative clinical translation.
The precise diagnosis and treatment of hepatocellular carcinoma (HCC) face major challenges such as the complexity of tumor microenvironment, treatment resistance, and a high risk of recurrence and metastasis. In recent years, ultrasound technology has moved beyond its traditional role in screening and localization, gradually evolving into a multidimensional therapeutic platform capable of energy activation, targeted delivery, local ablation, immune modulation, and therapeutic feedback. This article systematically reviews the latest advances in the basic research on ultrasound techniques in HCC treatment and integrated management. In terms of treatment, intervention strategies represented by microbubble/nanobubble-mediated delivery, sonodynamic therapy, high-intensity focused ultrasound, and histotripsy not only enable in situ physical destruction of lesions, but also effectively reverse tumor immune tolerance networks through deep synergy with sonogenetics, metabolic reprogramming, and immunochemotherapy. In terms of integrated management, novel sonosensitive nanodelivery systems provide a platform for energy activation and targeted controlled release. To address the translational bottlenecks in this field, it is recommended to develop standardized consensus on preclinical therapeutic ultrasound parameters, in order to establish a new translational paradigm for individualized precise diagnosis and treatment of HCC.
Hepatocellular carcinoma (HCC) often has an insidious onset, and early diagnosis and accurate differential diagnosis are critical for improving the prognosis of patients. Ultrasound remains an important radiological examination for the screening and initial assessment of high-risk populations due to its advantages of convenience, real-time monitoring, repeatability, and suitability for dynamic follow-up. With the development of ultrasound technologies in recent years, the application of ultrasound in HCC has gradually expanded from lesion detection to lesion characterization, differential diagnosis, and prognostic evaluation. With reference to the clinical needs for the early and differential diagnosis of HCC, this article reviews the application value, clinical localization, and limitations of gray-scale ultrasound, Doppler ultrasound, and contrast-enhanced ultrasound in HCC, with a focus on their application in the evaluation and differential diagnosis of small HCC. It highlights that comprehensive evaluation should be performed based on liver background, lesion morphology, blood flow features, enhancement patterns, and dynamic changes during follow-up, so as to improve the early and differential diagnosis of HCC.
As a common type of primary liver cancer, hepatocellular carcinoma (HCC) is a major health threat in China. Ultrasound is a crucial imaging modality in the clinical diagnosis and treatment of HCC, and the development and application of new ultrasound technologies have high clinical value. Currently, ultrasound and contrast-enhanced ultrasound combined with artificial intelligence have shown promising potential in the detection of focal liver lesions, image-based HCC diagnosis, outcome assessment, and prognostic prediction; furthermore, ultrasound fusion imaging technology has shown certain clinical value in guidance and efficacy evaluation of percutaneous thermal ablation; three-dimensional ultrasound has certain advantages in assisting ablation and assessing ablation margins; endoscopic ultrasonography can be used as a supplementary method for HCC cases that are difficult to scan or guide via percutaneous ultrasound.
Hepatocellular carcinoma (HCC) is one of the major malignancies with the heaviest disease burden in China. Many patients have lost the opportunity for radical surgical resection at the time of diagnosis, with locoregional interventional therapy playing an increasingly important role in full-course HCC management. Contrast-enhanced ultrasound (CEUS) enables real-time dynamic assessment of tumor microvascular perfusion and has several practical advantages including bedside availability, no ionizing radiation, and repeatability, and its role has therefore expanded from an adjunctive diagnostic method to the full-course management of precise locoregional diagnosis and treatment for HCC. Before treatment, CEUS can assist in the qualitative diagnosis of lesions, lesion localization, delineation of the viable tumor, and planning of the puncture route, especially for lesions that are poorly visualized on conventional ultrasound. During and after treatment, CEUS can help to detect residual viable tumor, related complications, and local tumor progression, thereby providing a basis for additional ablation, transcatheter arterial chemoembolization, or adjustment of combined treatment strategies. In recent years, the CEUS LI-RADS treatment response assessment system has provided a standardized framework for evaluating response after locoregional therapy, and in addition, the development of unimodal and multimodal fusion imaging techniques has further promoted the standardized application of CEUS in precise locoregional therapy for HCC. As increasing attention is paid to the ablation margin, the goal of response evaluation for local ablation has shifted from “the achievement of imaging-defined complete ablation” to a new treatment paradigm of “no contrast-enhanced imaging, no ablation; no fusion imaging, no curative ablation”. This article reviews the technical advantages, clinical application value, treatment response assessment, fusion imaging strategies, and current limitations of CEUS in locoregional interventional diagnosis and treatment of HCC, in order to provide a reference for the individualized and precise management of HCC.
Accurate assessment of treatment response after local ablation is of great importance for detecting residual viable tumor, evaluating ablative margins, and guiding subsequent follow-up and monitoring in patients with hepatocellular carcinoma (HCC). Contrast-enhanced computed tomography and magnetic resonance imaging are currently the main imaging modalities for post-ablation evaluation, but have certain limitations in real-time imaging, intraoperative application, and repeatability. Ultrasound, especially contrast-enhanced ultrasound (CEUS), can be used throughout the entire process of ablation therapy for HCC due to its advantages of real-time visualization of microvascular perfusion, no ionizing radiation, and repeatability, thereby playing an important role in detecting residual viable tumor, assessing immediate treatment response, and monitoring patients during follow-up. This article reviews the pathological basis and major endpoints of treatment response assessment after thermal ablation for HCC, with a focus on the clinical application of ultrasound techniques and the Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System Treatment Response Algorithm. In addition, it discusses the future development directions of multimodal imaging, quantitative assessment, and standardized evaluation, in order to provide a reference for further optimizing the treatment response assessment system for HCC after ablation.
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has a poor overall prognosis. Contrast-enhanced ultrasound (CEUS) plays a crucial role in the diagnosis, treatment response evaluation, and prognostic evaluation of HCC. This article systematically reviews the literature characteristics, research hotspots, and frontier advances of CEUS in the field of HCC. There has been a gradual increase in annual publication volume in this field, with China ranking first globally in the total number of publications. Highly cited articles mainly focus on clinical guidelines and standardized protocols. Keyword analysis shows that the main research hotspots in this field include the diagnosis and standardized assessment of HCC, differential diagnosis, treatment response evaluation after local therapy, and prognostic prediction. Meanwhile, microvascular invasion, artificial intelligence (AI), and super-resolution ultrasound (SRUS) may be emerging as cutting-edge frontiers in this field. Specifically, AI can be used for the auxiliary diagnosis of HCC, the evaluation of tumor biological characteristics, and prognostic prediction, and SRUS can overcome the acoustic diffraction limit to achieve precise microvascular imaging of the liver. Currently, a solid foundation has been established for the research on CEUS in HCC, showing a strong orientation toward clinical practice. In the future, emerging technologies such as CEUS-based AI models and SRUS are expected to further promote the development of precise diagnosis and treatment for HCC.
Chronic hepatitis B (CHB) is a significant public health issue worldwide. The persistent presence of covalently closed circular DNA of the hepatitis B virus (HBV) and the integration of the viral genome are the main obstacles limiting the achievement of virological cure in CHB. Functional cure has now become an important goal in antiviral therapy for CHB, and its accurate determination and efficacy prediction rely on a comprehensive assessment of multidimensional diagnostic markers. This article systematically reviews the research advances in diagnostic markers associated with functional cure in CHB, focusing on the clinical value of serological and virological indicators (HBsAg quantification and HBV DNA), genomic, transcriptomic, proteomic, and metabolomic markers, and indicators associated with host innate immunity and adaptive immunity. Furthermore, it discusses future research directions such as the establishment of unified detection standards and the construction of predictive models combining multiple markers, in order to promote the precise assessment and individualized management of functional cure in CHB.
In the context of immunosuppression, high-risk populations may develop hepatitis B virus (HBV) reactivation, leading to active hepatitis and even liver failure, which poses a threat to life. The initiation timing of prophylactic anti-HBV therapy is a frequent clinical challenge. This guideline aims to provide evidence-based practice recommendations for the management of HBV reactivation in high-risk populations in China.
Camrelizumab combined with apatinib has been approved by the National Medical Products Administration (NMPA) as a first-line therapeutic regimen for hepatocellular carcinoma (HCC), and a wealth of clinical research evidence and practical experience associated with liver cancer has been accumulated to date. To guide the rational and effective clinical administration of camrelizumab combined with apatinib for HCC treatment, Expert Committee for Liver Cancer and Expert Committee on Safety Management of Anti-Tumor Drugs, Chinese Society of Clinical Oncology, jointly organized multidisciplinary experts and scholars specializing in liver cancer and related disciplines nationwide. This expert consensus has been formulated after thorough discussions and repeated revisions, in order to provide standardized and evidence-based clinical guidance for clinicians.
On June 27, 2026, the Asian Pacific Association for the Study of the Liver (APASL) released updated management guidelines for chronic HBV infection, which systematically elaborates on screening, vaccination, antiviral treatment, and hepatocellular carcinoma surveillance and other aspects in 13 key areas, and provides comprehensive recommendations. This article summarizes and makes an excerpt of the key recommendations from the updated guidelines.
The American College of Radiology recently published the appropriateness criteria for initial imaging assessment of chronic pancreatitis (CP) and acute inflammation superimposed on CP (ACP). These criteria systematically elaborate on the role of various imaging modalities in diagnosing CP and ACP, assessing disease severity, identifying underlying causes, and evaluating complications, in order to provide guidance for effective management of CP patients through early and accurate imaging techniques and with reference to clinical and laboratory assessments. This article gives an excerpt of the key statements from the criteria.
In April 2026, the National Health Commission of the People’s Republic of China released Guidelines for the diagnosis and treatment of primary liver cancer (2026 edition). This edition incorporates an independent chapter of “prevention, screening, and monitoring” to build a hierarchical and precise prevention and control system, establishes a comprehensive therapeutic paradigm targeting surgical resection, and clarifies the core position of conversion therapy and neoadjuvant therapy. It also updates the recommendations for interventional and systemic therapies and strengthens the whole-course management of underlying liver diseases. This article interprets the key updates of this new edition to better guide clinical practice.
Autosomal dominant polycystic kidney disease (ADPKD) is a systemic hereditary renal disorder and can affect multiple organs, and congenital hepatic fibrosis is one of the manifestations of liver involvement and is an important complication of ADPKD. Symptomatic management is currently the main treatment method for this disease, and disease-specific drugs such as tolvaptan have limited indications and cannot correct the underlying genetic defect. This article reports a case of ADPKD with congenital hepatic fibrosis, and sirolimus was identified as the individualized treatment regimen based on peripheral blood functional genomic analysis and drug sensitivity prediction platform. The patient achieved significant improvements in symptoms and quality of life after treatment, with a stable kidney volume. This case shows that functional genomics has a potential value in guiding individualized treatment of rare genetic disorders, which provides new treatment ideas and practice paths for similar patients.
Metabolic associated fatty liver disease (MAFLD) has become one of the most prevalent chronic liver diseases worldwide, with the core pathological feature of pathological accumulation of triglycerides in hepatocytes, and as a key rate-limiting enzyme for triglyceride synthesis in the liver, 2-acylglycerol O-acyltransferase 2 (DGAT2) plays a central role in this process. Cell and animal model studies have confirmed that inhibition of DGAT2 can effectively alleviate hepatic steatosis and delay disease progression, and subsequent clinical trials have also shown the potential clinical application value in the treatment of MAFLD. This article systematically reviews the mechanism of action of DGAT2 in the development and progression of MAFLD and comprehensively summarizes the therapeutic strategies targeting DGAT2, including the advances in both monotherapy and drug combinations, in order to provide new ideas for individualized treatment of MAFLD patients.
Liver fibrosis is a key pathological stage in the progression of chronic liver diseases to liver cirrhosis, and effective etiological control or therapeutic interventions can help to achieve varying degrees of liver fibrosis regression in some patients. Accordingly, accurate assessment of the degree of liver fibrosis regression has gradually become an important concern in clinical management and the development of novel therapeutic agents. Conventional assessment methods mainly focus on fibrosis staging and have certain limitations in reflecting structural remodeling and dynamic changes of the liver. This article systematically reviews the recent research advances in the assessment of liver fibrosis regression from various aspects such as histological and digital pathology, serological and multi-omics biomarkers, and functional and molecular imaging modalities and discusses their respective advantages and limitations in assessing liver fibrosis regression. On this basis, this article discusses a multimodal integrated evaluation strategy based on artificial intelligence, in order to provide new ideas for accurate assessment of liver fibrosis regression, individualized therapeutic monitoring, and optimization of clinical trial endpoints.
The incidence rate of hepatic fibrosis remains at a high level, and there is still a lack of specific therapeutic drugs, posing a serious threat to human health. As a type of natural active components widely present in plants, flavonoids have multiple physiological functions such as antioxidant, anti-inflammatory, and anti-fibrotic activities, and a large number of studies have confirmed the anti-hepatic fibrosis effect of flavonoids. As for the mechanism of action, flavonoids can target the functions of hepatic stellate cells by inhibiting their proliferation and differentiation, promoting their apoptosis, regulating the level of autophagy, reducing the formation of extracellular matrix, and regulating iron metabolism in hepatic stellate cells, and meanwhile, they can inhibit chronic liver inflammatory response, improve oxidative stress status, regulate intestinal flora balance, and block epithelial-mesenchymal transition, thereby blocking the progression of fibrosis through multiple dimensions. At the level of signaling pathways, flavonoids mainly exert an anti-fibrotic effect by regulating the abnormal activation of the signaling pathways such as transforming growth factor-β1/Smad, Janus kinase/signal transducer and activator of transcription, nuclear factor erythroid 2-related factor 2, nuclear factor-kappa B, phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, Wnt/β-catenin, and adenosine 5'-monophosphate-activated protein kinase. This article summarizes the research advances in the anti-fibrotic effect of flavonoids, in order to provide a theoretical basis for further exploring their medicinal potential.
Hepatocellular carcinoma (HCC) imposes a significant global disease burden, and the development of HCC is closely associated with an immunosuppressive tumor microenvironment. Systemic therapy for advanced HCC has entered the era of immune combination therapy. The ORIENT-32 study has established the regimen of sintilimab combined with bevacizumab as the first-line therapy, and multiple real-world studies have confirmed its clinical value. Overcoming drug resistance remains a major challenge during the application of various combination regimens of targeted therapy and immunotherapy, including this particular regimen. Current research focus is gradually shifting toward deciphering its clinical phenotypes and molecular mechanisms, while promoting the clinical translation of biomarkers from static prediction to dynamic monitoring. In the future, overcoming drug resistance, optimizing combination strategies, and achieving precise individualized treatment are key to enhancing the survival benefit of patients. This article systematically evaluates the efficacy and safety of the sintilimab+bevacizumab regimen in a real-world setting, preliminarily discusses its drug resistance mechanism, and reviews the research advances in the biomarkers for predicting treatment response and guiding drug resistance overcoming, in order to provide a basis for optimizing the precise treatment strategies for advanced HCC.
Hepatocellular carcinoma (HCC) is a hepatic malignancy with a high mortality rate, and the development and progression of HCC is closely associated with gut microbiota and their metabolites. Butyrate is a kind of short-chain fatty acid produced by gut microbiota through metabolism, and it plays an important role in various aspects such as protecting intestinal barrier, regulating immune response, and exerting an antitumor effect. Notably, there is a reduction in the abundance of butyrogenic microbes and dysregulation of butyrate metabolism in patients with HCC, which provides new ideas for the treatment of HCC based on microbes and their metabolites. Current studies have preliminarily shown that butyrogenic microbes and butyrate exhibit both predictive and synergistic effects in the treatment of HCC and thus have broad prospects for clinical application. This article systematically elaborates on their characteristics in the progression of HCC, summarizes related research advances in their combination with systemic treatment strategies, and provides new insights for future research directions, in order to promote their clinical application.
Acute-on-chronic liver failure is an acute decompensated syndrome that occurs on the basis of chronic liver disease and is characterized by a high short-term mortality rate. Metabolomics reveals the presence of significant energy metabolic reprogramming, manifesting as extensive dysregulation of glucose/lipid/amino acid metabolism, mitochondrial metabolism, and intestinal flora, and it closely interacts with systemic inflammation and immune imbalance, jointly promoting disease progression. The core metabolic phenotypes include suppressed gluconeogenesis, enhanced glycolysis, impaired β-oxidation, inhibited mitochondrial oxidative phosphorylation, ammonia metabolic imbalance, and gut microbiota dysbiosis. This article analyzes the latest studies on metabolomic and molecular mechanisms and systematically reviews the dysregulation characteristics of the five major metabolic networks. In terms of intervention for energy metabolism, this article summarizes the five strategies of glucose metabolism regulation, lipid metabolism intervention, mitochondria-targeted protection, gut microbiota rebalancing, and amino-acid optimization and assesses their application value and prospects for clinical translation, so as to provide a scientific basis for the treatment, alleviation, and even reversal of disease progression.
Artificial liver support therapy for liver failure is often complicated by thrombocytopenia, which increases the risk of bleeding. This article systematically elaborates on the pathophysiological role of platelets in liver disease, and systematically analyzes the differential effect of various artificial liver support modalities on platelets, with a focus on key factors such as biocompatibility and anticoagulation strategies. This article also summarizes the clinical management approaches including individualized platelet transfusion and the application of thrombopoietic agents and discusses the value of platelet count as a predictive indicator for treatment safety and efficacy, in order to provide a basis for precise clinical intervention.
Intestinal permeability plays a pivotal role in the gut-liver axis and has emerged as a critical target for the prevention and treatment of liver diseases. Based on recent studies in China and globally, this article reviews the definitions and interrelationship of intestinal barrier function and intestinal permeability, the methods for assessing intestinal permeability, and the mechanism of action and clinical significance of intestinal permeability in the development and progression of various liver diseases. Studies have shown that increased intestinal permeability is a significant hallmark and an important driving factor for multiple liver diseases, and this state leads to the translocation of bacteria and harmful substances, trigger a systemic inflammatory response, and thus exacerbates liver injury, fibrosis, and metabolic dysregulation. Therefore, it is closely associated with the development and progression of metabolic associated fatty liver disease, alcoholic liver disease, autoimmune liver diseases, and their end-stage events, including liver cirrhosis, liver failure, and hepatocellular carcinoma. Future research should focus on the standardization of assessment methods, the exploration of underlying mechanisms, and the clinical translation of these findings.
Adipose tissue is a crucial endocrine and immune organ, and its functional dysregulation is closely associated with the development and progression of various liver diseases. In addition to the secretion of classical adipokines, adipose tissue-derived extracellular vesicles (EVs) have emerged as key messengers in its regulation of distal organ function. This review systematically elaborates on the regulatory role of adipose tissue-derived EVs in liver diseases, in which white adipose tissue delivers pathogenic molecules such as miR-103 and CD36 via its EVs and thus drives hepatic insulin resistance, lipid accumulation, and fibrosis, while brown adipose tissue transmits protective signals such as miR-132-3p through its EVs to improve hepatic metabolic homeostasis. This article also summarizes the core mechanisms of action of these EVs and discusses their potential as diagnostic biomarkers and innovative therapeutic strategies.
Pancreatic ductal adenocarcinoma (PDAC) is highly malignant and often has an extremely poor prognosis, and early postoperative liver metastasis is one of the key influencing factors for prognosis. With reference to the clinical and experimental studies in recent years, this article reviews the clinical risk factors for early liver metastasis after PDAC and systematically elaborates on major molecular events underlying early postoperative liver metastasis from various aspects of construction of the pre-metastatic niche in the liver driven by tumor-derived exosomes, the pro-metastatic microenvironment maintained by metastasis-associated macrophages and neutrophil extracellular traps, the invasive phenotype and liver-tropic migration of tumor cells, intrahepatic immunometabolic adaptation, and fibrotic remodeling, in order to provide a theoretical basis for perioperative risk stratification and the development of intervention strategies.
Top View Top DownloadMore>
- 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
- 6Congenital bile acid synthesis defect and cholestatic liver disease
- 7Relationship between Epstein-Barr virus infection and hepatic lesions in children
- 8Research state and prospect of hyponatremia in cirrhosis
- 9Interventional treatment for Budd-Chiari syndrome:reports of 883 cases
- 10
- 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)
- 4Current situation in the research of Gilbert’s syndrome
- 5
- 6Comprehensive guidelines for the diagnosis and treatment of pancreatic cancer (2018 version)
- 7Consensus on the diagnosis and management of primary biliary cirrhosis (cholangitis)(2015)
- 8Diagnosis, management, and treatment of hepatocellular carcinoma (V2017)
- 9Consensus on the diagnosis and management of autoimmune hepatitis(2015)
- 10Guidelines for the prevention and treatment of chronic hepatitis B (version 2019)
International Database
-
nbsp; -
荷兰《医学文摘(网络版)》(Embase)(2023—) -
荷兰《文摘与引文索引》(Scopus)(2021—) -
美国《生命科学引文索引》(BIOSIS Citation Index)(2025—)
美国《生命科学信息预览》(BIOSIS Previews)(2025—)
美国《生命科学文摘》(Biological Abstracts)(2025—) -
美国《ProQuest健康与医学资源全文数据库》 -
美国《化学文摘(网络版)》(CA)来源期刊(2011—) -
瑞士《健康网络首创研究获取》(HINARI)来源期刊(1985—) -
美国《艾博思科数据库》(Eh,EBSCOhost)来源期刊(2013—) -
英国《国际农业与生物科学研究中心》(CABI)来源期刊(2011—) -
ISSN国际中心《开放学术资源库》(ROAD)(2023—) -
世界卫生组织《西太平洋地区医学索引(WPRIM)》来源期刊(2016—) -
印度《J-Gate全球电子期刊获取门户》(J-Gate)(2026—) -
《日本科学技术振兴机构数据库(中国)》(JSTChina)来源期刊(2018—) -
俄罗斯《文摘杂志》(AJ,VINITI)来源期刊(2013—) -
美国《乌利希期刊指南(网络版)》(Ulrichsweb)注册期刊(2018—) -
英国《欧洲学术出版中心数据库》(EuroPub)来源期刊(2024—) -
波兰《哥白尼索引》(ICI)来源期刊(2011—)

Abstract
HTML
PDF (603KB)





