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Vol.42 No.9 (311 in total) Sep. 2026
Theme Issue: Liver Diseases and Hematologic Disorders
Executive Chief Editor: Wang Zhao
Beijing Friendship Hospital, Capital Medical University
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2026, 42(9): 2001-2005.
DOI: 10.12449/JCH260901
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Abstract:
Chronic active Epstein-Barr virus disease （CAEBVD） is a lymphoproliferative disorder caused by Epstein-Barr virus infection of T cells and natural killer cells. The liver is one of the most commonly affected organs in CAEBVD， with 47% to 67.1% of patients exhibiting varying degrees of liver injury. This article systematically reviews the characteristics of liver injury associated with CAEBVD from the aspects of its pathogenesis， clinical manifestations， pathological features， diagnostic criteria， treatment， and prognosis， in order to improve awareness of this disease among clinicians and promote early diagnosis and timely treatment.
Chronic active Epstein-Barr virus disease （CAEBVD） is a lymphoproliferative disorder caused by Epstein-Barr virus infection of T cells and natural killer cells. The liver is one of the most commonly affected organs in CAEBVD， with 47% to 67.1% of patients exhibiting varying degrees of liver injury. This article systematically reviews the characteristics of liver injury associated with CAEBVD from the aspects of its pathogenesis， clinical manifestations， pathological features， diagnostic criteria， treatment， and prognosis， in order to improve awareness of this disease among clinicians and promote early diagnosis and timely treatment.
2026, 42(9): 2006-2013.
DOI: 10.12449/JCH260902
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Hepatopathy-related thrombocytopenia （HRT） is a common complication in patients with chronic liver disease， and the development and progression of HRT involve multiple mechanisms including decreased platelet production， splenic sequestration， immune-mediated destruction， increased platelet consumption， and abnormalities in the bone marrow microenvironment. HRT not only increases the risk of bleeding but also hampers the successful implementation of antiviral therapy， antitumor treatment， and invasive procedures. In recent years， with the accumulation of evidence from basic and clinical studies， significant advances have been achieved in the pathogenesis， risk assessment， diagnostic stratification， and therapeutic strategies for HRT， and the paradigm of precise management has gradually shifted from merely increasing platelet counts toward a cause-directed， risk-stratified， and individualized intervention approach. With reference to the latest research advances in China and globally， this article reviews the new insights into the pathogenesis of HRT， refinements in diagnostic and risk assessment strategies， and the latest research advances in management strategies such as thrombopoietic agents， immunotherapy， invasive therapies， and integrated traditional Chinese and Western medicine therapies， in order to provide a reference for precise diagnosis， treatment， and clinical decision-making in HRT and to lay a foundation for establishing a future precise management system.
Hepatopathy-related thrombocytopenia （HRT） is a common complication in patients with chronic liver disease， and the development and progression of HRT involve multiple mechanisms including decreased platelet production， splenic sequestration， immune-mediated destruction， increased platelet consumption， and abnormalities in the bone marrow microenvironment. HRT not only increases the risk of bleeding but also hampers the successful implementation of antiviral therapy， antitumor treatment， and invasive procedures. In recent years， with the accumulation of evidence from basic and clinical studies， significant advances have been achieved in the pathogenesis， risk assessment， diagnostic stratification， and therapeutic strategies for HRT， and the paradigm of precise management has gradually shifted from merely increasing platelet counts toward a cause-directed， risk-stratified， and individualized intervention approach. With reference to the latest research advances in China and globally， this article reviews the new insights into the pathogenesis of HRT， refinements in diagnostic and risk assessment strategies， and the latest research advances in management strategies such as thrombopoietic agents， immunotherapy， invasive therapies， and integrated traditional Chinese and Western medicine therapies， in order to provide a reference for precise diagnosis， treatment， and clinical decision-making in HRT and to lay a foundation for establishing a future precise management system.
2026, 42(9): 2014-2021.
DOI: 10.12449/JCH260903
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The hemostatic function in patients with liver cirrhosis is not simply in a state of hypocoagulability， but rather a fragile rebalanced state resulting from the simultaneous remodeling of procoagulant and anticoagulant systems， the von Willebrand factor-platelet axis， and the fibrinolytic system. Since patients with liver cirrhosis frequently exhibit laboratory abnormalities including thrombocytopenia， prolonged prothrombin time/international normalized ratio， abnormal fibrinogen level， and elevated D-dimer， these manifestations substantially overlap with the laboratory phenotype of disseminated intravascular coagulation （DIC）， leading to potential misdiagnosis and unnecessary blood product transfusion or correction of coagulation parameters in clinical practice. Current evidence suggests that factor Ⅷ level and the widely used International Society on Thrombosis and Haemostasis DIC scoring system have limited value in differential diagnosis in patients with liver disease， and there is still a lack of a unified pathway for differential diagnosis. This article systematically reviews the pathophysiological overlap between rebalanced hemostasis in liver cirrhosis and DIC and summarizes the diagnostic value of conventional coagulation parameters， emerging hemostatic biomarkers， and global hemostatic assays in differential diagnosis of these conditions. Furthermore， it proposes a four-step diagnostic pathway of “trigger identification， baseline comparison， dynamic monitoring， and organ assessment” with reference to the specific clinical scenarios including infection， acute decompensation， gastrointestinal bleeding， hepatocellular carcinoma， and the perioperative period. In the future， DIC prediction models based on the features of liver disease should be established in combination with viscoelastic testing and multidimensional biomarkers， so as to achieve precise risk stratification and individualized management of coagulation abnormalities in patients with liver cirrhosis.
The hemostatic function in patients with liver cirrhosis is not simply in a state of hypocoagulability， but rather a fragile rebalanced state resulting from the simultaneous remodeling of procoagulant and anticoagulant systems， the von Willebrand factor-platelet axis， and the fibrinolytic system. Since patients with liver cirrhosis frequently exhibit laboratory abnormalities including thrombocytopenia， prolonged prothrombin time/international normalized ratio， abnormal fibrinogen level， and elevated D-dimer， these manifestations substantially overlap with the laboratory phenotype of disseminated intravascular coagulation （DIC）， leading to potential misdiagnosis and unnecessary blood product transfusion or correction of coagulation parameters in clinical practice. Current evidence suggests that factor Ⅷ level and the widely used International Society on Thrombosis and Haemostasis DIC scoring system have limited value in differential diagnosis in patients with liver disease， and there is still a lack of a unified pathway for differential diagnosis. This article systematically reviews the pathophysiological overlap between rebalanced hemostasis in liver cirrhosis and DIC and summarizes the diagnostic value of conventional coagulation parameters， emerging hemostatic biomarkers， and global hemostatic assays in differential diagnosis of these conditions. Furthermore， it proposes a four-step diagnostic pathway of “trigger identification， baseline comparison， dynamic monitoring， and organ assessment” with reference to the specific clinical scenarios including infection， acute decompensation， gastrointestinal bleeding， hepatocellular carcinoma， and the perioperative period. In the future， DIC prediction models based on the features of liver disease should be established in combination with viscoelastic testing and multidimensional biomarkers， so as to achieve precise risk stratification and individualized management of coagulation abnormalities in patients with liver cirrhosis.
2026, 42(9): 2022-2028.
DOI: 10.12449/JCH260904
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Severe liver disease is frequently accompanied by prolonged prothrombin time or international normalized ratio， thrombocytopenia， and abnormal fibrinogen level， which have traditionally been interpreted as hypocoagulability and a bleeding tendency. Recent studies have shown that hemostatic abnormalities in liver disease do not simply result from deficiency of procoagulant factors， but represent a fragile rebalanced hemostatic state shaped by multiple mechanisms including parallel reductions in procoagulant factors and natural anticoagulants， platelet and fibrinolytic abnormalities， imbalance of the von Willebrand factor/a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13 axis， and endothelial activation. This article reviews the key mechanisms of rebalanced hemostasis in severe liver disease， the limitations of conventional coagulation markers， coagulation features across different disease states， and their implications for clinical management. Clinical decision-making should shift from correcting abnormal laboratory values to identifying destabilization of the inflammation-endothelium-coagulation-fibrinolysis network， with individualized assessment based on disease stage and the risk of bleeding/thrombosis.
Severe liver disease is frequently accompanied by prolonged prothrombin time or international normalized ratio， thrombocytopenia， and abnormal fibrinogen level， which have traditionally been interpreted as hypocoagulability and a bleeding tendency. Recent studies have shown that hemostatic abnormalities in liver disease do not simply result from deficiency of procoagulant factors， but represent a fragile rebalanced hemostatic state shaped by multiple mechanisms including parallel reductions in procoagulant factors and natural anticoagulants， platelet and fibrinolytic abnormalities， imbalance of the von Willebrand factor/a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13 axis， and endothelial activation. This article reviews the key mechanisms of rebalanced hemostasis in severe liver disease， the limitations of conventional coagulation markers， coagulation features across different disease states， and their implications for clinical management. Clinical decision-making should shift from correcting abnormal laboratory values to identifying destabilization of the inflammation-endothelium-coagulation-fibrinolysis network， with individualized assessment based on disease stage and the risk of bleeding/thrombosis.
2026, 42(9): 2029-2033.
DOI: 10.12449/JCH260905
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There is a bidirectional relationship between liver diseases and hemolytic anemia. Liver diseases may cause or aggravate erythrocyte destruction through abnormalities in erythrocyte membrane lipids， copper toxicity， oxidative stress， mechanical injury， and immune dysregulation； conversely， some primary hemolytic diseases may initially present with abnormalities in the hepatobiliary system due to jaundice， bile pigment stones， splenomegaly， or thrombosis of the splanchnic veins. Hemolysis is classified into intravascular hemolysis and extravascular hemolysis according to the predominant site of erythrocyte destruction； however， the two processes may coexist and may change with disease stage or treatment. Hemolysis associated with Wilson’s disease and acute liver failure， paroxysmal nocturnal hemoglobinuria， and some cases of hemolysis after transjugular intrahepatic portosystemic shunt are characterized by intravascular destruction； spur cell anemia， hereditary erythrocyte membrane disorders， and warm-antibody autoimmune hemolytic anemia are mainly characterized by extravascular destruction； Zieve syndrome， glucose-6-phosphate dehydrogenase deficiency， some cases of autoimmune hemolytic anemia， and passenger lymphocyte syndrome after liver transplantation may involve both pathways of hemolysis. With the site of hemolysis as the primary framework and the immune versus non-immune mechanisms as a supplementation， this article reviews hemolysis associated with liver diseases and primary hemolytic disorders that may present with hepatobiliary abnormalities and proposes a therapeutic approach based on stratified diagnosis and etiology.
There is a bidirectional relationship between liver diseases and hemolytic anemia. Liver diseases may cause or aggravate erythrocyte destruction through abnormalities in erythrocyte membrane lipids， copper toxicity， oxidative stress， mechanical injury， and immune dysregulation； conversely， some primary hemolytic diseases may initially present with abnormalities in the hepatobiliary system due to jaundice， bile pigment stones， splenomegaly， or thrombosis of the splanchnic veins. Hemolysis is classified into intravascular hemolysis and extravascular hemolysis according to the predominant site of erythrocyte destruction； however， the two processes may coexist and may change with disease stage or treatment. Hemolysis associated with Wilson’s disease and acute liver failure， paroxysmal nocturnal hemoglobinuria， and some cases of hemolysis after transjugular intrahepatic portosystemic shunt are characterized by intravascular destruction； spur cell anemia， hereditary erythrocyte membrane disorders， and warm-antibody autoimmune hemolytic anemia are mainly characterized by extravascular destruction； Zieve syndrome， glucose-6-phosphate dehydrogenase deficiency， some cases of autoimmune hemolytic anemia， and passenger lymphocyte syndrome after liver transplantation may involve both pathways of hemolysis. With the site of hemolysis as the primary framework and the immune versus non-immune mechanisms as a supplementation， this article reviews hemolysis associated with liver diseases and primary hemolytic disorders that may present with hepatobiliary abnormalities and proposes a therapeutic approach based on stratified diagnosis and etiology.
2026, 42(9): 2034-2038.
DOI: 10.12449/JCH260906
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Autoimmune hepatitis （AIH） is an immune-mediated inflammatory injury of the hepatic parenchyma targeting hepatocytes. In recent years， the incidence rate of AIH has tended to increase year by year. To further unify and refine the traditional Chinese medicine （TCM） diagnostic and therapeutic pathways and standards for AIH and to improve the clinical efficacy of TCM in the treatment of AIH， this guideline was developed by the drafting group based on evidence-based medicine in accordance with the requirements of TCM standardization and relevant technical guidance documents for the reference of clinicians. This guideline was approved and issued by China Association of Chinese Medicine， with the standard number of T/CACM 1630-2024.
Autoimmune hepatitis （AIH） is an immune-mediated inflammatory injury of the hepatic parenchyma targeting hepatocytes. In recent years， the incidence rate of AIH has tended to increase year by year. To further unify and refine the traditional Chinese medicine （TCM） diagnostic and therapeutic pathways and standards for AIH and to improve the clinical efficacy of TCM in the treatment of AIH， this guideline was developed by the drafting group based on evidence-based medicine in accordance with the requirements of TCM standardization and relevant technical guidance documents for the reference of clinicians. This guideline was approved and issued by China Association of Chinese Medicine， with the standard number of T/CACM 1630-2024.
2026, 42(9): 2039-2048.
DOI: 10.12449/JCH260907
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Primary liver cancer is one of the most common malignancies in China， with hepatocellular carcinoma （HCC） accounting for the vast majority of these cases. Advanced HCC has complex clinical manifestations and diverse treatment modalities， posing great challenges to clinical diagnosis and treatment. Currently， there is still a lack of an expert consensus specifically focusing on integrated traditional Chinese and Western medicine clinical collaboration for advanced HCC in China. To standardize the diagnosis and treatment process of advanced HCC based on integrated traditional Chinese and Western medicine collaboration and improve the homogeneity of advanced HCC management in Yunnan Province， Hepatology Committee of Yunnan Hospital Association convened multidisciplinary experts from gastroenterology， hepatobiliary surgery， interventional radiology， medical oncology， radiation oncology， traditional Chinese medicine， ethnic medicine and hospice care to formulate this consensus based on the best evidence available and with reference to local ethnic medicine and clinical practice in Yunnan. This consensus covers various aspects of advanced HCC， including diagnosis， staging， systemic therapy， locoregional therapy， antiviral therapy， traditional Chinese medicine and ethnic medicine interventions， multidisciplinary collaboration， quality control， and humanistic care.
Primary liver cancer is one of the most common malignancies in China， with hepatocellular carcinoma （HCC） accounting for the vast majority of these cases. Advanced HCC has complex clinical manifestations and diverse treatment modalities， posing great challenges to clinical diagnosis and treatment. Currently， there is still a lack of an expert consensus specifically focusing on integrated traditional Chinese and Western medicine clinical collaboration for advanced HCC in China. To standardize the diagnosis and treatment process of advanced HCC based on integrated traditional Chinese and Western medicine collaboration and improve the homogeneity of advanced HCC management in Yunnan Province， Hepatology Committee of Yunnan Hospital Association convened multidisciplinary experts from gastroenterology， hepatobiliary surgery， interventional radiology， medical oncology， radiation oncology， traditional Chinese medicine， ethnic medicine and hospice care to formulate this consensus based on the best evidence available and with reference to local ethnic medicine and clinical practice in Yunnan. This consensus covers various aspects of advanced HCC， including diagnosis， staging， systemic therapy， locoregional therapy， antiviral therapy， traditional Chinese medicine and ethnic medicine interventions， multidisciplinary collaboration， quality control， and humanistic care.
2026, 42(9): 2049-2054.
DOI: 10.12449/JCH260908
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Steatotic liver disease is characterized by substantial heterogeneity in etiology， metabolic background， and pathological progression， and no single model can fully recapitulate the spectrum of human disease. There are currently various preclinical models， yet further standardization is needed in terms of nomenclature， model selection， experimental conditions， and assessment indices. Issued by the European Association for the Study of the Liver， this 2026 position paper systematically reviews the in vivo， in vitro， and ex vivo models of metabolic dysfunction-associated steatotic liver disease， metabolic dysfunction and alcohol-associated liver disease， and alcohol-associated liver disease. It proposes the selection of models based on disease subtype， research objective， and target endpoint and provides recommendations for pharmacological positive controls， experimental design， histopathological assessment， and minimum reporting requirements. This article gives an excerpt of the key contents of the position paper， so as to facilitate standardized selection and evaluation of preclinical models for steatotic liver disease and improve their concordance with human disease phenotypes.
Steatotic liver disease is characterized by substantial heterogeneity in etiology， metabolic background， and pathological progression， and no single model can fully recapitulate the spectrum of human disease. There are currently various preclinical models， yet further standardization is needed in terms of nomenclature， model selection， experimental conditions， and assessment indices. Issued by the European Association for the Study of the Liver， this 2026 position paper systematically reviews the in vivo， in vitro， and ex vivo models of metabolic dysfunction-associated steatotic liver disease， metabolic dysfunction and alcohol-associated liver disease， and alcohol-associated liver disease. It proposes the selection of models based on disease subtype， research objective， and target endpoint and provides recommendations for pharmacological positive controls， experimental design， histopathological assessment， and minimum reporting requirements. This article gives an excerpt of the key contents of the position paper， so as to facilitate standardized selection and evaluation of preclinical models for steatotic liver disease and improve their concordance with human disease phenotypes.
2026, 42(9): 2055-2058.
DOI: 10.12449/JCH260909
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On July 1， 2026， Hepatology International published online the APASL clinical practice guidance on the diagnosis and management of patients with Wilson’s disease. The guidance formulates 22 recommendations for Wilson’s disease from the aspects of clinical manifestations， laboratory and imaging diagnostics， genetic testing， family screening， lifestyle modifications， pharmacotherapy， liver transplantation， pregnancy management， and care for asymptomatic/presymptomatic patients. This article systematically reviews the core contents of this guidance， with a particular focus on the excerpted recommendations for diagnosis and treatment， in order to provide a practical reference for the clinical identification， diagnosis， and long-term management of patients with Wilson’s disease.
On July 1， 2026， Hepatology International published online the APASL clinical practice guidance on the diagnosis and management of patients with Wilson’s disease. The guidance formulates 22 recommendations for Wilson’s disease from the aspects of clinical manifestations， laboratory and imaging diagnostics， genetic testing， family screening， lifestyle modifications， pharmacotherapy， liver transplantation， pregnancy management， and care for asymptomatic/presymptomatic patients. This article systematically reviews the core contents of this guidance， with a particular focus on the excerpted recommendations for diagnosis and treatment， in order to provide a practical reference for the clinical identification， diagnosis， and long-term management of patients with Wilson’s disease.
2026, 42(9): 2059-2066.
DOI: 10.12449/JCH260910
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Objective To clarify the independent and synergistic effects of dyslipidemia in the progression of hepatic steatosis in metabolic dysfunction-associated fatty liver disease （MAFLD）. Methods A total of 7 697 participants who underwent physical examination in Beijing Friendship Hospital， Capital Medical University， from January 2022 to December 2024 were enrolled， and finally 2 177 patients with MAFLD were enrolled as subjects. Transient elastography was used to quantify the severity of hepatic steatosis （grades S1-S3）. The multivariable ordinal Logistic regression analysis was used to investigate the independent and synergistic associations of serum triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） with the severity of hepatic steatosis， and their interactions and potential nonlinear relationships with metabolic factors were also examined. One-way analysis of variance or Kruskal-Wallis H test was used for comparison of continuous data between groups， and chi-square test was used for comparison of categorical data between groups. Results An increase in TG （odds ratio ［OR］=1.77， 95% confidence interval ［CI］： 1.48 — 2.10， P<0.001） and a reduction in HDL-C （OR=1.35， 95%CI： 1.11 — 1.65， P=0.003） were independently associated with a greater severity of hepatic steatosis， with the strongest association when both abnormalities coexisted （OR=2.40， 95%CI： 1.87 — 3.07， P<0.001）. The dose-response relationship analysis further revealed a nonlinear threshold effect of TG on hepatic steatosis at the threshold of 1.51 mmol/L （Pnonlinearity=0.001）， below which the severity of steatosis increased more rapidly with the increase in TG concentration （P=0.001）. The subgroup analysis showed that the association between the reduction in HDL-C and the severity of steatosis was observed only in males， young adults （aged <45 years）， and metabolically healthier subgroups （without diabetes， obesity， hyperuricemia or hypertension）. Significant interactions were observed between the presence or absence of obesity and the abnormal levels of TG and HDL‑C （both Pinteraction<0.05）. The association of the increase in LDL-C with steatosis was confined to specific subgroups （without obesity or hyperuricemia）. Conclusion The increase in TG and the reduction in HDL-C are independently associated with the severity of hepatic steatosis in MAFLD. The synergistic effect of blood lipids and their interactions with metabolic factors may further refine risk stratification， so as to provide a basis for precise management of MAFLD.
2026, 42(9): 2067-2074.
DOI: 10.12449/JCH260911
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Objective To identify protein biomarkers and potential therapeutic targets associated with metabolic dysfunction-associated fatty liver disease （MAFLD） through an integrative multi-omics analysis. Methods Large-scale plasma protein quantitative trait locus data were integrated with MAFLD genome-wide association study data， and a proteome-wide Mendelian randomization analysis was performed. Summary data-based Mendelian Randomization （SMR）/heterogeneity in dependent instruments （HEIDI） test and colocalization analysis were used to assess significant proteins. The independent samples t-test was used for comparison of continuous data with homogeneity of variance between two groups， and the Welch-corrected t-test was used for comparison of continuous data with heterogeneity of variance. The transcriptomic validation results were compared with the Mendelian randomization results to evaluate the changing trends of gene expression， and boxplots were used to display the expression distribution of candidate genes between groups. Results Among 7 130 proteins analyzed， 40 showed a causal relationship with MAFLD， among which 26 increased the risk of MAFLD and 14 exerted a protective effect against MAFLD （FDR<0.05）. Nine proteins were supported by SMR/HEIDI （PSMR<0.05， PHEIDI>0.05）， and 14 showed a strong colocalization signal （PPH4>0.9）. The transcriptomic analysis identified 5 differentially expressed proteins （all P<0.05）， i.e.， adenosine diphosphate-ribosylation factor-like GTPase 2， insulin-like growth factor binding protein 2， casein kinase 1 delta （CSNK1D）， leucine-rich repeat neuronal 1， and moesin （MSN）. In vitro validation showed upregulated expression levels of MSN （1.612±0.346 vs 0.569±0.077， P<0.05）， 14-3-3 protein theta （YWHAQ） （1.267±0.126 vs 0.313±0.029， P<0.05）， and CSNK1D （0.871±0.025 vs 0.431±0.080， P<0.05） and a downregulated expression level of histone deacetylase 8 （0.637±0.059 vs 1.097±0.260， P<0.05） in the MAFLD cell model. Functional annotation showed that CSNK1D participated in circadian and metabolic regulation， YWHAQ modulated the Hippo pathway and lipid signal transduction， and MSN was associated with cytoskeletal remodeling and fibrogenic responses. Conclusion The integrative proteogenomic analysis in this study shows that CSNK1D， YWHAQ， and MSN may be key mediators in the pathogenesis of MAFLD. These proteins have the potential to serve as novel biomarkers and therapeutic targets， providing new directions for research on disease mechanisms and the development of intervention strategies.
2026, 42(9): 2075-2085.
DOI: 10.12449/JCH260912
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Objective To screen for and validate key differentially expressed proteins in serum of patients with metabolic dysfunction‑associated fatty liver disease （MAFLD）， and to provide a basis for identifying diagnostic biomarkers and developing intervention strategies for this disease. Methods A total of 20 patients who were diagnosed with MAFLD in the third affiliated hospital of Chengdu University of Traditional Chinese Medicine from December 2024 to January 2025 were enrolled as MAFLD group， and 20 healthy controls were enrolled as HC group. Demographic data and serum biochemical parameters were collected from both groups. Data-independent acquisition （DIA） quantitative proteomics was used to measure the relative expression levels of serum proteins， and related methods were used to obtain significantly differentially expressed proteins， including the gene ontology functional enrichment analysis， the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis， protein-protein interaction （PPI） network， Hub node interaction， and weighted gene co-expression network analysis （WGCNA）. Rats were given a high-fat diet to establish a model of MAFLD， and randomly assigned to the control group and model group. Serum biochemical parameters and inflammatory factors were measured， liver histopathological changes were observed， and the protein expression levels of MER proto-oncogene tyrosine kinase （MERTK） and matrix metalloproteinase-9 （MMP-9） in liver tissue were verified. The independent-samples t test was used for comparison of normally distributed continuous data between groups， while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or data with heterogeneity of variance between groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. Results Compared with the HC group， the MAFLD group had significant increases in the serum levels of aspartate aminotransferase （t=-7.348， P<0.05）， alanine aminotransferase （Z=5.088， P<0.05）， alkaline phosphatase （t=-3.943， P<0.05）， triglyceride （Z=2.070， P<0.05）， and high-density lipoprotein cholesterol （t=3.867， P<0.05）. A total of 3 559 proteins were identified by DIA serum proteomics， among which 160 differentially expressed proteins were mainly enriched in pathways including metabolic disorders， immune inflammatory response， and extracellular matrix remodeling. The PPI network and the Hub node analysis showed that serpin family E member 1， MMP-9， and intercellular cell adhesion molecule-1 were core regulatory proteins. WGCNA showed that the MEyellow module was significantly positively correlated with MAFLD phenotype （cor=0.55， P<0.001）， which was functionally enriched in the efferocytosis pathway. MERTK （P<0.001） and MMP-9 （P<0.001） showed the most significant differential expression in this module. A rat model of MAFLD was successfully established using a high-fat diet， and compared with the control group， the model group had enlarged， yellowish， and greasy liver and disordered structure of hepatic lobules， hepatocyte fatty degeneration， and inflammatory cell infiltration based on HE staining， as well as massive lipid droplet deposition based on oil red O staining， while no obvious fibrous cords were observed in Masson staining. Compared with the control group， the model group had significant increases in the serum levels of aspartate aminotransferase （t=-5.148， P<0.05）， alanine aminotransferase （t=-5.663， P<0.05）， total bilirubin （t=-13.061， P<0.05）， triglyceride （Z=-2.722， P<0.05）， total cholesterol （t=3.588， P<0.05）， and tumor necrosis factor-α （t=-16.741， P<0.05）， as well as significant increases in the protein expression levels of MERTK （t=-11.448， P<0.001） and MMP-9 （t=-10.875， P<0.001） in liver tissue. Conclusion MMP-9 and MERTK are abnormally expressed in MAFLD and may be used as potential diagnostic biomarkers for this disease.
2026, 42(9): 2086-2092.
DOI: 10.12449/JCH260913
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Objective To investigate the value of serum adiponectin （ADPN）， retinol-binding protein 4 （RBP4）， and neutrophil-to-lymphocyte ratio （NLR） in assessing metabolic dysfunction-associated steatohepatitis （MASH）， and to provide a reference for clinical prevention. Methods A total of 298 patients with metabolic dysfunction-associated fatty liver disease （MAFLD） who attended The Third Hospital of Shanxi Medical University from January 2023 to January 2025 were enrolled as subjects. A Logistic regression analysis was used to investigate the predictive factors for MASH， and R language rms package was used to construct a nomogram. The receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis were used to evaluate model accuracy and practicality， and a Pearson correlation analysis was used to investigate the correlation between various indicators. The chi-square test was used for comparison of categorical data between groups； the independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. Results A total of 298 MAFLD patients were enrolled， among whom there were 95 patients with MASH and 203 patients with simple steatosis. The multivariate Logistic regression analysis showed that alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， RBP4， ADPN， and NLR were independent influencing factors for MASH （all P<0.05）. A nomogram model was constructed based on the above factors， and the ROC curve analysis showed that the model had an area under the ROC curve of 0.985 （95% confidence interval： 0.976 — 0.995）， with a sensitivity of 0.968 and a specificity of 0.901. The calibration curve analysis showed no significant difference between the predicted and actual probabilities based on the Hosmer-Lemeshow goodness-of-fit test （χ2=2.905， P=0.940）， suggesting that the model had good fit and high predictive accuracy. The decision curve analysis showed that the model achieved net benefit when the risk threshold was >0.05. The Pearson correlation analysis showed that in MASH patients， serum RBP4 was negatively correlated with ADPN （r=-0.275， P<0.001） and was positively correlated with NLR （r=0.282， P<0.001）， and ADPN was negatively correlated with NLR （r=-0.221， P<0.001）. Conclusion ALT， ALP， RBP4， ADPN， and NLR are independent influencing factors for MASH. It is necessary in clinical practice to enhance monitoring， identify high-risk patients as early as possible， and provide timely intervention， so as to reduce the incidence rate of MASH and the risk of disease progression.
2026, 42(9): 2093-2105.
DOI: 10.12449/JCH260914
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Objective To investigate whether macrophage lipolysis-stimulated lipoprotein receptor （LSR） deficiency affects the progression of metabolic dysfunction-associated steatohepatitis （MASH） by activating the Yes-associated protein （YAP） signaling pathway. Methods Male wild-type （WT） mice and macrophage-specific Lsr knockout （LsrMφKO， KO） mice， with an age of 8 weeks and similar body weights， were selected and fed with a normal diet， a high-fat diet （HFD）， or a high-fat high-cholesterol （HFHC） diet for 30 weeks. HE staining and oil red O staining were used to evaluate liver pathological changes； immunofluorescent staining was used to measure the expression levels of F4/80 and α-smooth muscle actin； RT-qPCR and Western blot were used to measure the levels of markers associated with lipid metabolism， inflammation， and fibrosis. Bone marrow transplantation rescue experiments （WT→KO vs KO→KO groups） were conducted to explore the functional role of LSR in macrophages. At the cellular level， hepatic macrophages were isolated from WT and KO mice to measure the expression levels of YAP signaling pathway-related proteins and their downstream target genes， and in addition， these cells were treated in vitro with verteporfin （VP）， a specific inhibitor of YAP， to verify the regulatory effect of this pathway on the expression of inflammatory factors. The independent samples t-test was used for comparison of normally distributed measurement data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data. Results Under the condition of normal diet， there were no significant differences in hepatic indicators between WT and KO mice. KOmice fed an HFD or HFHC diet showed a significant increase in hepatic lipid droplet accumulation， accompanied by lipid metabolism disorder and significant increases in the levels of indicators associated with inflammation and fibrosis （P<0.05）. Bone marrow transplantation experiments confirmed that compared with the KO→KO group， the WT→KO group had significant alleviation of liver injury （P<0.05）. Mechanistic studies showed that there were significant reductions in the levels of phosphorylated large tumor suppressor kinase 1 （LATS1） and phosphorylated YAP and significant increases in the expression levels of total YAP protein and its downstream target genes in hepatic macrophages of KO mice （P<0.05）. In vitro VP intervention significantly inhibited the expression levels of inflammatory factors in hepatic macrophages isolated from KO mice （P<0.05）. Conclusion Macrophage LSR deficiency activates the YAP signaling pathway by inhibiting LATS1/2 kinase activity and promotes the expression of inflammatory factors， thereby accelerating the progression of liver injury in a mouse model of MASH.
2026, 42(9): 2106-2115.
DOI: 10.12449/JCH260915
Abstract:
Objective To investigate the distribution and characteristics of traditional Chinese medicine （TCM） syndromes in patients with colorectal cancer and metabolic dysfunction-associated fatty liver disease （CRC-MAFLD）， to explore the correlation between influencing factors and syndrome distribution， and to provide a reference for clinical syndrome differentiation. Methods A total of 319 patients who were admitted to Shanxi Provincial Institute of Traditional Chinese Medicine and The Affiliated Hospital of Shanxi University of Chinese Medicine from January 2021 to December 2025 and were diagnosed with CRC-MAFLD based on pathology and radiological examination were enrolled as subjects， and TCM syndrome differentiation was performed for all subjects. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between multiple groups. The indicators with statistical significance in the univariate analysis were incorporated into the unordered multinomial Logistic regression model， and the syndrome of liver depression and spleen deficiency was set as the reference group to identify the independent influencing factors for each TCM syndrome. Results The main clinical symptoms of CRC-MAFLD included fatigue （78.06%）， abdominal distension （64.26%）， poor appetite （61.13%）， loose stool （57.05%）， and costal pain （52.04%）. The syndrome of liver depression and spleen deficiency showed the highest distribution frequency， followed by intermingled phlegm and blood stasis， internal retention of dampness turbidity， damp-heat accumulation， deficiency of liver and kidney， and deficiency of spleen and kidney. Comparison between groups with different TCM syndromes showed significant differences in the distribution of body mass index （χ2=42.216， P<0.001）， the clinical stage of colorectal cancer （χ2=11.666， P=0.040）， liver metastasis （χ2=19.279， P=0.002）， degree of hepatic steatosis （χ2=71.085， P<0.001）， diabetes （χ2=12.486， P=0.029）， chemotherapy （χ2=21.920， P<0.001）， fasting plasma glucose （FPG） （F=10.367， P<0.001）， glycosylated hemoglobin （HbA1c） （F=3.696， P=0.003）， albumin （Alb） （F=3.302， P=0.006）， alkaline phosphatase （ALP） （H=34.350， P<0.001）， gamma-glutamyl transferase （GGT） （H=41.679， P<0.001）， and triglyceride （TG） （H=28.826， P<0.001）. An unordered multinomial Logistic regression model was constructed with the syndrome of liver depression and spleen deficiency as the reference， and the results showed that overweight/obesity was a common independent risk factor for intermingled phlegm and blood stasis （odds ratio ［OR］=4.468， P=0.002）， internal retention of dampness turbidity （OR=2.944， P=0.024）， and damp-heat accumulation （OR=5.651， P=0.001）； clinical stage Ⅳ was an independent risk factor for deficiency of liver and kidney （OR=6.746， P=0.003） and deficiency of spleen and kidney （OR=10.074， P=0.001）； presence of liver metastasis was an independent risk factor for intermingled phlegm and blood stasis （OR=5.145， P=0.001）； severe fatty liver disease was an independent risk factor for intermingled phlegm and blood stasis （OR=5.201， P=0.007） and internal retention of dampness turbidity （OR=7.412， P=0.001）， and moderate fatty liver disease was an independent risk factor for intermingled phlegm and blood stasis （OR=2.643， P=0.045）， internal retention of dampness turbidity （OR=3.182， P=0.029）， and damp-heat accumulation （OR=3.073， P=0.036）； diabetes was an independent risk factor for internal retention of dampness turbidity （OR=5.133， P=0.003） and damp-heat accumulation （OR=3.716， P=0.031）. As for continuous variables， elevated FPG was an independent risk factor for internal retention of dampness turbidity （OR=2.375， P=0.003） and damp-heat accumulation （OR=2.701， P=0.005）； elevated HbA1c was an independent risk factor for intermingled phlegm and blood stasis （OR=2.029， P=0.032） and deficiency of liver and kidney （OR=3.308， P=0.010）； elevated ALP was an independent risk factor for damp-heat accumulation （OR=1.053， P=0.019）； elevated GGT was an independent risk factor for intermingled phlegm and blood stasis （OR=1.029， P=0.026） and damp-heat accumulation （OR=1.030， P=0.047）； elevated TG was an independent risk factor for intermingled phlegm and blood stasis （OR=2.931， P=0.006） and internal retention of dampness turbidity （OR=2.449， P=0.019）； elevated Alb was a protective factor against deficiency of spleen and kidney （OR=0.756， P=0.005）. Conclusion Body mass index， the clinical stage of colorectal cancer， liver metastasis， degree of hepatic steatosis， diabetes， chemotherapy， FPG， HbA1c， Alb， ALP， GGT， and TG are the main influencing factors for TCM syndromes in CRC-MAFLD.
2026, 42(9): 2116-2125.
DOI: 10.12449/JCH260916
Abstract:
Objective To investigate the effect of trophoblast-derived mesenchymal stem cell （T-MSC） on concanavalin A （Con A）-induced immune-mediated liver injury in mice， as well as its association with the changes in inflammatory response. Methods Morphological assessment， flow cytometry， and tri-lineage differentiation assay were used to observe the biological characteristics of T-MSC. In the pilot experiment， mice were divided into PBS group， T-MSC monotherapy group， and Con A groups at a concentration of 10， 15， or 20 mg/kg to evaluate the safety of T-MSC monotherapy on liver function and determine the appropriate dose for modeling. In the formal experiment， mice were divided into healthy control group （HC group）， Con A group， and Con A+T-MSC group， with 5 mice in each group. The mice were given injection of Con A （15 mg/kg） via the caudal vein to establish a mouse model of immune-mediated liver injury， while the mice in the T-MSC monotherapy group were given transfusion of 1×106 T-MSCs via the caudal vein at 3 hours after modeling， and samples were collected 12 hours later. The serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and lactate dehydrogenase （LDH） were measured； liver histopathological changes were observed， and Ishak inflammatory activity score and inflammatory necrosis area were assessed； the serum levels of inflammatory cytokines were measured； transcriptome sequencing， immunofluorescence assay， and Western blot were used to measure the changes in inflammation-related molecules in liver tissue. The Shapiro-Wilk test was used to assess the normality of continuous data， and the homogeneity of variance test was also performed； a one-way analysis of variance was used for comparison of normally distributed data with homogeneity of variance between multiple groups， and the Tukey’s post-hoc test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed data with heterogeneity of variance between multiple groups， and the Wilcoxon test was used for further comparison between two groups. Results T-MSC had a long spindle shape， showed the characteristics of fibroblast-like morphology and adherent growth， and possessed the osteogenic， chondrogenic， and adipogenic differentiation abilities. Flow cytometry showed high expression levels of CD90， CD105， and CD73 in T-MSC， with a positive rate of 96.8%， 99.0%， and 99.9%， respectively， while there was low or no expression of CD31， human leukocyte antigen DR， CD45， and CD34， with a positive rate of 0.120%， 0， 0.061%， and 0， respectively. Administration of T-MSC alone did not cause obvious abnormalities in ALT， AST， or LDH. Con A at the concentrations of 10， 15， and 20 mg/kg all increased the serum levels of biochemical parameters for liver injury in a dose-dependent manner， with mortality observed in the 20 mg/kg group. In the formal experiment， compared with the HC group， the Con A group had significant increases in the serum levels of ALT， AST， and LDH （P<0.01）， and after T-MSC treatment， there were significant reductions in these markers compared with the Con A group （P<0.01）. HE staining showed that the Con A group had disordered structure of the liver， accompanied by marked inflammatory cell infiltration and focal/patchy necrosis， and these pathological changes were alleviated after T-MSC treatment. Compared with the HC group， the Con A group had significant increases in Ishak score and the percentage of inflammatory necrosis area （P<0.001）， while there were significant reductions in these indicators after T-MSC treatment compared with the Con A group （P<0.01）. ELISA showed that compared with the HC group， the Con A group had significant increases in the serum levels of interleukin-21 （IL-21）， interleukin-1β （IL-1β）， interleukin-2 （IL-2）， interleukin-17A （IL-17A）， and tumor necrosis factor-α （TNF-α） （P<0.05）， and there were significant reductions in these markers after T-MSC treatment compared with the Con A group （P<0.05）， with no significant differences in IL-21， IL-1β， IL-17A， and TNF-α compared with the HC group （P>0.05）； although there was a significant reduction in the level of IL-2， the Con A+T-MSC group still had a significantly higher level of IL-2 than the HC group （P=0.001）. In contrast， compared with the HC group， the Con A group had a significant increase in IL-10 （P<0.05）， with a further increase after T-MSC treatment （P<0.05）. The transcriptome analysis showed that T-MSC treatment downregulated the expression of the inflammation- and chemokine-related genes including Ccl2， Cxcl10， Il-21， and Il-6 and inhibited the inflammation-related pathways such as TNF， IL-17， nuclear factor-κB， and JAK-STAT. Immunofluorescence assay showed that compared with the HC group， the Con A group had a significant increase in the expression of IL-21 in the liver （P<0.001）， and there was a significant reduction in IL-21 after T-MSC treatment compared with the Con A group （P<0.001）； the results of Western blot showed the same trend. Conclusion T-MSC can alleviate Con A-induced immune-mediated liver injury in mice， as evidenced by the improvement in liver biochemical parameters， the alleviation of histopathological damage， and the overall downregulation of inflammation-related molecules. T-MSC exerts marked anti-inflammatory and immunomodulatory effects in this model， and IL-21 shows a significant change in inflammatory response and can be used as a candidate molecule for further investigation.
2026, 42(9): 2126-2134.
DOI: 10.12449/JCH260917
Abstract:
Objective To investigate the value of albumin-bilirubin （ALBI） score combined with platelet count-to-spleen thickness ratio （PC/ST） in predicting rebleeding within one year after endoscopic variceal ligation in liver cirrhosis patients with esophagogastric variceal bleeding （EVB）， to evaluate the risk assessment ability of this model， and to provide a reference for clinical prevention of rebleeding. Methods A retrospective analysis was performed on the clinical data of liver cirrhosis patients with EVB who were hospitalized in Gansu Provincial Hospital from January 1， 2020 to December 31， 2024. All patients achieved successful hemostasis after endoscopic variceal ligation， and according to whether rebleeding occurred within one year after surgery， they were divided into rebleeding group and non-rebleeding group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The univariate and multivariate Cox regression analyses were used to identify independent influencing factors for rebleeding. A prediction model was constructed based on the factors identified， and a nomogram was plotted for model visualization. The receiver operating characteristic （ROC） curve was used to assess the discriminatory ability of the model， and the area under the ROC curve （AUC） was calculated； calibration curve was used to assess calibration； decision curve analysis was used to assess the net clinical benefit of the model. Results A total of 258 patients were enrolled， among whom 70 patients experienced rebleeding within one year， resulting in a rebleeding rate of 27.1%. The multivariate Cox regression analysis showed that ALBI score （hazard ratio ［HR］=4.679， 95% confidence interval ［CI］： 2.952 — 7.417， P<0.001） and PC/ST （HR=0.461， 95%CI： 0.318 — 0.668， P<0.001） were independent influencing factors for rebleeding in liver cirrhosis patients with EVB. The model constructed based on these two factors yielded an AUC of 0.766 （95%CI： 0.667 — 0.866）， 0.775 （95%CI： 0.699 — 0.851）， and 0.809 （95%CI： 0.752 — 0.866）， respectively， for predicting the risk of rebleeding at 6 weeks， 6 months， and 1 year. The calibration curve showed that the model systematically underestimated the probability of rebleeding at 6 weeks and 6 months， but its prediction for the probability of rebleeding at 1 year aligned well with the ideal curve. The decision curve analysis showed that the model provided a clear net clinical benefit for predicting rebleeding within 1 year. Conclusion The model constructed based on ALBI score and PC/ST had good performance in predicting the risk of rebleeding within 1 year after endoscopic variceal ligation in liver cirrhosis patients with EVB.
2026, 42(9): 2135-2142.
DOI: 10.12449/JCH260918
Abstract:
Objective To compare the application value of two endoscopic ultrasound （EUS）-guided targeted vascular embolization techniques in secondary prevention of esophagogastric variceal bleeding （EGVB）， and to clarify the clinical advantages of targeted main trunk embolization. Methods A retrospective analysis was performed for 59 patients who were admitted to Beijing Ditan Hospital， Capital Medical University， from April 2023 to July 2024 and received secondary prevention of gastroesophageal varices （GOV）-type EGVB， and according to the surgical procedure， they were divided into EUS-PCSS targeting the distal segment of the source vessel or perforating branch vessels （EUS-PCSS-D/P） group with 29 patients and EUS-PCSS targeting the source vascular trunk （EUS-PCSS-T） group with 30 patients. The two groups were observed in terms of rebleeding rate， variceal eradication efficiency， and the incidence rate of adverse events. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups； the Mann-Whitney U test was used for subgroup analysis， and ordinal Logistic regression was used for multivariate analysis. Results There were no significant differences in baseline data between the two groups （all P>0.05）. Compared with the EUS-PCSS-D/P group， the EUS-PCSS-T group had a significantly smaller diameter of punctured vessels （5.39±2.03 mm vs 7.00±2.21 mm， t=3.012， P=0.005）， a significantly lower treatment rate of supplementary endoscopic injection sclerotherapy （EIS） （40.00% vs 79.31%， χ2=7.521， P=0.006）， and a significantly lower amount of lauromacrogol used （16.08±7.25 mL vs 22.17±6.83 mL， t=2.518， P=0.015）， and there were no significant differences between the two groups in the amount of tissue adhesive used， the number of puncture sites， and treatment costs （all P>0.05）. There were no significant differences between the two groups in rates of GOV-related and all-cause gastrointestinal rebleeding （all P>0.05）. Compared with the EUS-PCSS-D/P group， the EUS-PCSS-T group had a significantly lower number of treatment sessions required for GOV eradication （2.00 ［1.25 — 2.00］ vs 3.00 ［2.00 — 4.00］， Z=3.872， P<0.001）， with a higher two-session eradication rate （50.00% vs 17.86%， χ2=7.102， P=0.008） and a lower eradication rate for three or more sessions （23.33% vs 71.43%， χ2=15.326， P<0.001）. The subgroup analysis showed that history of endoscopic treatment and supplementary EIS did not affect the number of treatment sessions required for GOV regression （all P>0.05）， and the ordinal Logistic regression analysis showed that treatment grouping was an independent influencing factor for the number of treatment sessions required for GOV regression （odds ratio=0.32， 95% confidence interval： 0.15 — 0.68， P=0.007）. There was no significant difference in the incidence rate of adverse events between the two groups （P>0.05）， and no ectopic embolism was observed in the EUS-PCSS-T group. Conclusion The EUS-PCSS-T procedure can significantly improve the eradication efficiency of GOV and reduce the number of treatment sessions； its efficacy is not affected by history of endoscopic treatment or supplementary EIS therapy， and it has a favorable safety profile.
2026, 42(9): 2143-2153.
DOI: 10.12449/JCH260919
Abstract:
Objective To investigate the independent risk factors for concurrent myocardial injury before intervention in patients with primary hepatic carcinoma （PHC）， to construct and validate a nomogram prediction model for the early identification of such patients， and to provide a basis for early clinical prevention and management. Methods A retrospective analysis was performed for the clinical data of 1 822 patients with PHC in two medical institutions from January 2019 to June 2025， among whom the 1 518 patients from The Third People’s Hospital of Kunming were used as the training set to construct the nomogram prediction model， and the 304 patients from The Second People’s Hospital of Baoshan were used as the validation set. According to the result of high-sensitivity cardiac troponin T measurement before intervention， the patients with PHC were divided into myocardial injury group and non-myocardial injury group. The univariate analysis， the LASSO regression analysis， and the multivariate Logistic regression analysis were used to identify the risk factors of concurrent myocardial injury in PHC patients before intervention， and then a nomogram prediction model was constructed based on these findings. The independent data of the 304 patients in the validation set were used for external validation， and the area under the receiver operating characteristic curve （AUC）， the Hosmer-Lemeshow test， the calibration curve， decision curve analysis， and clinical impact curve were used to assess model performance. Results In the training set， there were 346 patients in the myocardial injury group and 1 172 patients in the non-myocardial injury group， and the prevalence rate of concurrent myocardial injury was 22.79%. The mean age was 56.44±9.45 years， and the male patients accounted for 81.49%. The patients with drinking， smoking， chronic hepatitis B， chronic hepatitis C， hypertension， diabetes， Child-Pugh class A liver disease， BCLC stage B liver disease， or abnormal electrocardiographic findings accounted for 49.34%， 57.44%， 61.73%， 32.48%， 22.66%， 17.19%， 50.53%， 33.86%， and 62.12%， respectively. The univariate analysis， the LASSO regression analysis， and the multivariate Logistic regression analysis showed that age （odds ratio ［OR］=1.051， 95% confidence interval ［CI］： 1.036 — 1.067， P<0.001）， history of diabetes （OR=1.862， 95%CI： 1.346 — 2.574， P<0.001）， electrocardiographic findings （OR=1.446， 95%CI： 1.077 — 1.940， P=0.014）， hemoglobin （HGB） （OR=0.993， 95%CI： 0.988 — 0.998， P=0.003）， albumin （Alb） （OR=0.951， 95%CI： 0.930 — 0.972， P<0.001）， and creatinine （Cr） （OR=1.021， 95%CI： 1.016 — 1.026， P<0.001） were independent influencing factors for myocardial injury in PHC patients. A regression equation was established as Logit（Y）=-3.406+0.050×age+0.621×history of diabetes+0.369×electrocardiogram－0.007×HGB－0.051×Alb+0.021×Cr， and a nomogram prediction model was constructed based on these factors. The Bootstrap internal validation of the model yielded an AUC of 0.743 （95%CI： 0.707 — 0.778）， and the model had an AUC of 0.766 （95%CI： 0.738 — 0.794） in the training set and 0.730 （95%CI： 0.688 — 0.793） in the validation set. The Hosmer-Lemeshow goodness-of-fit test yielded a P value of 0.716 for the training set and 0.408 for the validation set， suggesting that the model had a good degree of fitting. Calibration curves， decision curve analysis， and clinical impact curves in both the training set and the validation set showed that the model had a good clinical application value. Conclusion Age， history of diabetes， electrocardiographic findings， HGB， Alb， and Cr are independent influencing factors for myocardial injury in patients with PHC， and the nomogram prediction model constructed based on these factors has good discriminatory ability， accuracy， and clinical practicability.
2026, 42(9): 2154-2161.
DOI: 10.12449/JCH260920
Abstract:
Objective To investigate the association between sarcopenia and short-term prognosis in patients with acute-on-chronic liver failure （ACLF）， to assess the value of Model for End-Stage Liver Disease （MELD）， MELD combined with serum sodium concentration （MELD-Na）， MELD 3.0， and Chinese Group on the Study of Severe Hepatitis B （COSSH）-ACLF Ⅱ score in predicting the 90-day prognosis of ACLF patients， and to analyze the predictive gain of sarcopenia over traditional prognostic scoring models. Methods A retrospective study was conducted among 219 patients with ACLF who were hospitalized in The Affiliated Hospital of Inner Mongolia Medical University， No. 2 Hospital of Hohhot， Hohhot First Hospital， and Inner Mongolia People’s Hospital from July 2018 to July 2024. L3 skeletal muscle index （L3-SMI） was measured and calculated based on abdominal computed tomography images， and sarcopenia was diagnosed based on L3-SMI. According to 90-day prognosis， the patients with ACLF were divided into survival group with 124 patients and death group with 95 patients. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups； the independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The multivariate Cox regression analysis （stepwise backward approach） was used to identify independent risk factors for 90-day mortality in ACLF patients. The Kaplan-Meier method was used for survival analysis， and the Log-rank test was used for comparison between groups. The receiver operating characteristic curve was plotted to evaluate the predictive performance of each model， and the DeLong test， bootstrap internal validation， net reclassification improvement （NRI）， and integrated discrimination improvement （IDI） were used to assess the predictive gain of sarcopenia. Results The multivariate Cox regression analysis showed that presence of sarcopenia （hazard ratio ［HR］=3.385， 95% confidence interval ［CI］： 1.722 — 6.657， P<0.05）， older age （HR=1.036， 95%CI： 1.017 — 1.056， P<0.05）， elevated alkaline phosphatase （HR=1.006， 95%CI： 1.004 — 1.009， P<0.05）， elevated total bilirubin （HR=1.003， 95%CI： 1.001 — 1.005， P<0.05）， elevated potassium （HR=1.581， 95%CI： 1.160 — 2.155， P<0.05）， elevated serum creatinine （HR=1.015， 95%CI： 1.007 — 1.024， P<0.05）， and prolonged prothrombin time （HR=1.035， 95%CI： 1.015 — 1.055， P<0.05） were independent risk factors for 90-day mortality in ACLF patients， while elevated albumin （HR=0.885， 95%CI： 0.837 — 0.935， P<0.05） was an independent protective factor against 90-day mortality. MELD， MELD-Na， MELD 3.0， and COSSH-ACLF Ⅱ scores had an area under the ROC curve （AUC） of 0.569， 0.570， 0.632， and 0.659， respectively， for predicting the 90-day prognosis of ACLF patients， suggesting that these scores had unsatisfactory performance； after they were respectively combined with sarcopenia， the AUC was increased to 0.702， 0.687， 0.723， and 0.728， respectively. The DeLong test， NRI， and IDI analyses showed the combined models had significantly better predictive performance （all P<0.05）. Conclusion Sarcopenia is an independent risk factor for 90-day mortality in patients with ACLF. Traditional scoring models have limited predictive performance for 90-day prognosis in ACLF patients， and the combination with sarcopenia significantly improves predictive value， suggesting that sarcopenia can be used as an important supplementary indicator for prognostic evaluation of ACLF in clinical practice.
2026, 42(9): 2162-2170.
DOI: 10.12449/JCH260921
Abstract:
Objective To investigate the regulatory effect of miR-21-5p in bone marrow mesenchymal stem cell-derived exosome （BMSC-Exo） on angiogenesis through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. Methods Bone marrow mesenchymal stem cells （BMSCs） were isolated from rats， cultured， and divided into negative control group （NC group） and inhibitor group， which were transfected with miR-21-5p negative control and miR-21-5p inhibitor， respectively， and then exosomes were extracted and identified. Exosomes were co-cultured with human umbilical vein endothelial cells （HUVECs）. MTT assay was used to measure cell proliferation （24， 48， and 72 hours）， tube formation assay was used to assess angiogenesis ability， and Western blot was used to measure the protein expression levels of phosphorylated Akt （p-Akt）， total Akt， and vascular endothelial growth factor （VEGF）. The change in the angiogenesis ability of HUVECs was observed after treatment with the PI3K inhibitor LY294002. The independent samples t-test was used for comparison of continuous data between two groups， and a one-way analysis of variance was used for comparison between multiple groups， while the least significant difference t-test was used for further comparison between two groups. Results Flow cytometry showed that the third-generation BMSCs showed high expression levels of CD29 （98.18%） and CD90 （97.85%） and a low expression level of CD45 （0.22%）. Quantitative real-time reverse transcription-polymerase chain reaction showed that compared with the NC group， there was a significant reduction in the relative expression level of miR-21-5p in BMSCs after transfection with miR-21-5p inhibitor （0.38±0.05 vs 1.00±0.08， t=11.38， P<0.01）. MTT assay showed that compared with the control group， the 25， 50， 100， and 200 μg/mL exosome treatment groups had a significant increase in the proliferative activity of HUVECs （all P<0.05）， among which 100 μg/mL exosome treatment for 72 hours showed the most significant pro-proliferative effect， while the 400 μg/mL exosome treatment group showed a significant reduction in the proliferative activity of HUVECs （P<0.01）. Tube formation assay showed that compared with the control group and the NC-Exo group， the inhibitor-Exo group showed a significant reduction in angiogenesis ability （both P<0.05）， and compared with the inhibitor-Exo group， there was a further significant reduction in angiogenesis ability after addition of the PI3K inhibitor LY294002 （P<0.01）. Western blot showed that compared with the control group and the NC-Exo group， the inhibitor-Exo group had significant reduction in the protein expression levels of p-Akt and VEGF （all P<0.05）， and compared with the inhibitor-Exo group， the protein expression levels of p-Akt and VEGF further decreased significantly after the addition of LY294002 （both P<0.01）. Conclusion BMSC-Exo targets and activates the PI3K/Akt signaling pathway through miR-21-5p， upregulates the expression of VEGF， and promotes vascular endothelial cell proliferation and angiogenesis.
2026, 42(9): 2171-2175.
DOI: 10.12449/JCH260922
Abstract:
Hereditary hemochromatosis （HH） is a hereditary disease characterized by iron overload resulting from mutations in genes involved in iron metabolism. Type ⅣA HH， also known as classical ferroportin disease， is caused by loss-of-function mutations in the SLC40A1 gene and has the clinical manifestations of a significant increase in serum ferritin， normal or low transferrin saturation， and marked iron deposition in the spleen. This article reports a case of type ⅣA HH with a significant asymptomatic increase in serum ferritin. Magnetic resonance imaging showed that the severity of iron overload in the spleen was significantly higher than that in the liver； liver biopsy showed mild fatty liver disease and iron deposition in Kupffer cells； gene variation analysis identified a heterozygous mutation in SLC40A1 c.485_487del （p.Val162del）. Screening of family members showed that the proband’s mother carried the same variation and had the manifestation of iron overload in the liver and spleen， which further confirmed the pathogenicity of this variation. This case highlights that type ⅣA HH often has an insidious onset and is frequently misdiagnosed. For patients with an unexplained persistent increase in serum ferritin， active genetic testing for HH should be considered， even in the presence of concurrent liver diseases， in order to realize early diagnosis and intervention.
Hereditary hemochromatosis （HH） is a hereditary disease characterized by iron overload resulting from mutations in genes involved in iron metabolism. Type ⅣA HH， also known as classical ferroportin disease， is caused by loss-of-function mutations in the SLC40A1 gene and has the clinical manifestations of a significant increase in serum ferritin， normal or low transferrin saturation， and marked iron deposition in the spleen. This article reports a case of type ⅣA HH with a significant asymptomatic increase in serum ferritin. Magnetic resonance imaging showed that the severity of iron overload in the spleen was significantly higher than that in the liver； liver biopsy showed mild fatty liver disease and iron deposition in Kupffer cells； gene variation analysis identified a heterozygous mutation in SLC40A1 c.485_487del （p.Val162del）. Screening of family members showed that the proband’s mother carried the same variation and had the manifestation of iron overload in the liver and spleen， which further confirmed the pathogenicity of this variation. This case highlights that type ⅣA HH often has an insidious onset and is frequently misdiagnosed. For patients with an unexplained persistent increase in serum ferritin， active genetic testing for HH should be considered， even in the presence of concurrent liver diseases， in order to realize early diagnosis and intervention.
2026, 42(9): 2176-2182.
DOI: 10.12449/JCH260923
Abstract:
Metabolic dysfunction-associated fatty liver disease （MAFLD） is the chronic liver disease with the highest prevalence rate globally， and its disease spectrum encompasses a progressive continuum from hepatic steatosis to metabolic dysfunction-associated steatohepatitis， liver fibrosis， liver cirrhosis， and eventually hepatocellular carcinoma. In recent years， the research paradigm of MAFLD has shifted from “lipid accumulation” to “lipid metabolic reprogramming”， which， as a critical link in disease development and progression， is regulated by multidimensional molecular networks. This article systematically reviews the molecular mechanisms of lipid metabolic reprogramming in MAFLD from the following aspects： it analyzes the core role of lipid metabolism disorders， with a focus on how dysregulation of membranous organelle interactions， such as endoplasmic reticulum-mitochondria contacts， mediates metabolic imbalance； it concentrates on novel programmed cell death pathways induced by lipotoxicity， especially ferroptosis， and reveals the pathways through which they exacerbate liver injury； furthermore， it comprehensively analyzes the multi-layered regulatory network of the key signaling pathways such as adenosine monophosphate-activated protein kinase and nuclear factor-erythroid 2-related factor 2 and explores the emerging mechanisms such as liquid-liquid phase separation and microprotein regulation； finally， it provides an outlook on the potential therapeutic strategies targeting critical nodes of lipid metabolic reprogramming， so as to provide a theoretical basis for investigating the pathological mechanisms of MAFLD and developing precise interventions.
Metabolic dysfunction-associated fatty liver disease （MAFLD） is the chronic liver disease with the highest prevalence rate globally， and its disease spectrum encompasses a progressive continuum from hepatic steatosis to metabolic dysfunction-associated steatohepatitis， liver fibrosis， liver cirrhosis， and eventually hepatocellular carcinoma. In recent years， the research paradigm of MAFLD has shifted from “lipid accumulation” to “lipid metabolic reprogramming”， which， as a critical link in disease development and progression， is regulated by multidimensional molecular networks. This article systematically reviews the molecular mechanisms of lipid metabolic reprogramming in MAFLD from the following aspects： it analyzes the core role of lipid metabolism disorders， with a focus on how dysregulation of membranous organelle interactions， such as endoplasmic reticulum-mitochondria contacts， mediates metabolic imbalance； it concentrates on novel programmed cell death pathways induced by lipotoxicity， especially ferroptosis， and reveals the pathways through which they exacerbate liver injury； furthermore， it comprehensively analyzes the multi-layered regulatory network of the key signaling pathways such as adenosine monophosphate-activated protein kinase and nuclear factor-erythroid 2-related factor 2 and explores the emerging mechanisms such as liquid-liquid phase separation and microprotein regulation； finally， it provides an outlook on the potential therapeutic strategies targeting critical nodes of lipid metabolic reprogramming， so as to provide a theoretical basis for investigating the pathological mechanisms of MAFLD and developing precise interventions.
2026, 42(9): 2183-2190.
DOI: 10.12449/JCH260924
Abstract:
Metabolic dysfunction-associated fatty liver disease （MAFLD） is currently the most prevalent chronic liver disease worldwide， and its disease spectrum encompasses simple steatosis， metabolic-associated steatohepatitis， hepatic fibrosis， liver cirrhosis， and hepatocellular carcinoma. Recent studies have shown that hepatic macrophages play an important regulatory role in the development and progression of MAFLD. Hepatic macrophages mainly consist of resident Kupffer cells and monocyte-derived macrophages， which participate in the pathophysiological processes of the disease by regulating inflammatory response， lipid metabolism， fibrogenic process， and cell death pathways. This article summarizes the diversity and functional plasticity of hepatic macrophages in MAFLD， reviews their interactions with hepatocytes and gut microbiota， elaborates on the core mechanism of hepatic macrophages and related signaling pathways in the progression of MAFLD， and further discusses novel therapeutic strategies targeting hepatic macrophages. An in-depth understanding of the mechanism of action of hepatic macrophages in MAFLD may provide a crucial theoretical basis for developing precise therapeutic approaches for this disease.
Metabolic dysfunction-associated fatty liver disease （MAFLD） is currently the most prevalent chronic liver disease worldwide， and its disease spectrum encompasses simple steatosis， metabolic-associated steatohepatitis， hepatic fibrosis， liver cirrhosis， and hepatocellular carcinoma. Recent studies have shown that hepatic macrophages play an important regulatory role in the development and progression of MAFLD. Hepatic macrophages mainly consist of resident Kupffer cells and monocyte-derived macrophages， which participate in the pathophysiological processes of the disease by regulating inflammatory response， lipid metabolism， fibrogenic process， and cell death pathways. This article summarizes the diversity and functional plasticity of hepatic macrophages in MAFLD， reviews their interactions with hepatocytes and gut microbiota， elaborates on the core mechanism of hepatic macrophages and related signaling pathways in the progression of MAFLD， and further discusses novel therapeutic strategies targeting hepatic macrophages. An in-depth understanding of the mechanism of action of hepatic macrophages in MAFLD may provide a crucial theoretical basis for developing precise therapeutic approaches for this disease.
2026, 42(9): 2191-2196.
DOI: 10.12449/JCH260925
Abstract:
Metabolic dysfunction-associated fatty liver disease is a common chronic liver disease worldwide， and its incidence rate continues to rise. The traditional “two-hit” theory has gradually been replaced by the “multiple-hit” hypothesis， which emphasizes the synergistic effect of multiple pathogenic factors. Necroptosis is an inflammatory form of death with both the morphological characteristics of necrosis and the signaling mechanism of apoptosis， and the core of necroptosis lies in the receptor-interacting protein kinase 1-receptor-interacting protein kinase 3-mixed lineage kinase domain-like pseudokinase signaling axis. This pathway directly leads to the death of hepatocytes， and it triggers an inflammatory response and promotes the fibrosis process by releasing damage-associated molecular patterns； the pathway is also closely associated with the metabolic reprogramming of the liver. This review summarizes the activation mechanism of necroptosis in metabolic dysfunction-associated fatty liver disease， analyzes its effect on liver inflammation， fibrosis， and metabolism， and explores its therapeutic strategies and application prospects.
Metabolic dysfunction-associated fatty liver disease is a common chronic liver disease worldwide， and its incidence rate continues to rise. The traditional “two-hit” theory has gradually been replaced by the “multiple-hit” hypothesis， which emphasizes the synergistic effect of multiple pathogenic factors. Necroptosis is an inflammatory form of death with both the morphological characteristics of necrosis and the signaling mechanism of apoptosis， and the core of necroptosis lies in the receptor-interacting protein kinase 1-receptor-interacting protein kinase 3-mixed lineage kinase domain-like pseudokinase signaling axis. This pathway directly leads to the death of hepatocytes， and it triggers an inflammatory response and promotes the fibrosis process by releasing damage-associated molecular patterns； the pathway is also closely associated with the metabolic reprogramming of the liver. This review summarizes the activation mechanism of necroptosis in metabolic dysfunction-associated fatty liver disease， analyzes its effect on liver inflammation， fibrosis， and metabolism， and explores its therapeutic strategies and application prospects.
2026, 42(9): 2197-2202.
DOI: 10.12449/JCH260926
Abstract:
Metabolic dysfunction-associated fatty liver disease （MAFLD） is a chronic liver condition worldwide mainly caused by overnutrition and insulin resistance （IR）. It encompasses a broad disease spectrum with a high incidence rate and may further progress to hepatitis， liver cirrhosis， and hepatocellular carcinoma. The pathogenesis of MAFLD involves multiple factors， but the specific mechanism of action has not yet been fully elucidated. This article reviews the cutting-edge theory of “gut-liver axis dysfunction-hepatic iron overload”， summarizes the molecular mechanisms by which these two factors regulate intrahepatic lipotoxicity， oxidative stress， IR， and ferroptosis， reveals the pathophysiological process by which they synergistically promote the progression of MAFLD， and elaborates on the therapeutic strategies for MAFLD on this basis， so as to provide a reference for clinical diagnosis and treatment.
Metabolic dysfunction-associated fatty liver disease （MAFLD） is a chronic liver condition worldwide mainly caused by overnutrition and insulin resistance （IR）. It encompasses a broad disease spectrum with a high incidence rate and may further progress to hepatitis， liver cirrhosis， and hepatocellular carcinoma. The pathogenesis of MAFLD involves multiple factors， but the specific mechanism of action has not yet been fully elucidated. This article reviews the cutting-edge theory of “gut-liver axis dysfunction-hepatic iron overload”， summarizes the molecular mechanisms by which these two factors regulate intrahepatic lipotoxicity， oxidative stress， IR， and ferroptosis， reveals the pathophysiological process by which they synergistically promote the progression of MAFLD， and elaborates on the therapeutic strategies for MAFLD on this basis， so as to provide a reference for clinical diagnosis and treatment.
2026, 42(9): 2203-2208.
DOI: 10.12449/JCH260927
Abstract:
Metabolic dysfunction-associated fatty liver disease （MAFLD） has become the leading chronic liver disease worldwide. As a classic food-medicine homologous Chinese herb， hawthorn fruit has the functions of promoting digestion to resolve food stagnation and activating blood circulation to resolve blood stasis. Modern pharmacological studies have shown that hawthorn fruit and its active components exert diverse pharmacological activities in regulating lipid metabolism， improving insulin resistance， inhibiting inflammatory response， delaying hepatic fibrosis， and protecting hepatocytes. These effects precisely match the “multiple-hit” pathological features of MAFLD， and thus hawthorn fruit shows significant advantages in the prevention and treatment of MAFLD. Drug pair combination is a key strategy in traditional Chinese medicine to enhance efficacy and reduce toxicity. In clinical practice， hawthorn fruit is often combined with Salvia miltiorrhiza， Alisma orientalis， cassia seed， and Poria cocos， and such combination adheres to the principle of “mutual reinforcement and assistance” to enhance efficacy and expand their application in different syndromes of MAFLD. This article systematically reviews the core pharmacological mechanisms of hawthorn fruit in intervening against MAFLD and the research advances in its classic drug combinations， in order to provide a scientific reference for the in-depth development of hawthorn fruit and its combinations and the precise clinical intervention of MAFLD.
Metabolic dysfunction-associated fatty liver disease （MAFLD） has become the leading chronic liver disease worldwide. As a classic food-medicine homologous Chinese herb， hawthorn fruit has the functions of promoting digestion to resolve food stagnation and activating blood circulation to resolve blood stasis. Modern pharmacological studies have shown that hawthorn fruit and its active components exert diverse pharmacological activities in regulating lipid metabolism， improving insulin resistance， inhibiting inflammatory response， delaying hepatic fibrosis， and protecting hepatocytes. These effects precisely match the “multiple-hit” pathological features of MAFLD， and thus hawthorn fruit shows significant advantages in the prevention and treatment of MAFLD. Drug pair combination is a key strategy in traditional Chinese medicine to enhance efficacy and reduce toxicity. In clinical practice， hawthorn fruit is often combined with Salvia miltiorrhiza， Alisma orientalis， cassia seed， and Poria cocos， and such combination adheres to the principle of “mutual reinforcement and assistance” to enhance efficacy and expand their application in different syndromes of MAFLD. This article systematically reviews the core pharmacological mechanisms of hawthorn fruit in intervening against MAFLD and the research advances in its classic drug combinations， in order to provide a scientific reference for the in-depth development of hawthorn fruit and its combinations and the precise clinical intervention of MAFLD.
2026, 42(9): 2209-2216.
DOI: 10.12449/JCH260928
Abstract:
Autoimmune hepatitis （AIH） is a type of liver parenchymal inflammation mediated by an autoimmune response targeting hepatocytes， and autoantibodies are one of the key biomarkers for the clinical diagnosis of AIH. With reference to the new guidelines for AIH released by the European Association for the Study of the Liver and the British Society of Gastroenterology in 2025， this article introduces the recommendations for AIH subtyping， anti-nuclear antibody detection methods， and applicability of simplified scoring criteria and systematically reviews the characteristics of target antigens of autoantibodies associated with AIH and their roles in the diagnosis， treatment， and disease assessment of AIH. It also points out that identifying new specific biomarkers is an urgent issue in AIH research.
Autoimmune hepatitis （AIH） is a type of liver parenchymal inflammation mediated by an autoimmune response targeting hepatocytes， and autoantibodies are one of the key biomarkers for the clinical diagnosis of AIH. With reference to the new guidelines for AIH released by the European Association for the Study of the Liver and the British Society of Gastroenterology in 2025， this article introduces the recommendations for AIH subtyping， anti-nuclear antibody detection methods， and applicability of simplified scoring criteria and systematically reviews the characteristics of target antigens of autoantibodies associated with AIH and their roles in the diagnosis， treatment， and disease assessment of AIH. It also points out that identifying new specific biomarkers is an urgent issue in AIH research.
2026, 42(9): 2217-2223.
DOI: 10.12449/JCH260929
Abstract:
Primary biliary cholangitis （PBC） is an autoimmune-mediated chronic cholestatic liver disease. Ursodeoxycholic acid （UDCA） is the first-line treatment drug for PBC， yet some patients with suboptimal biochemical response to UDCA face a significant increase in the risk of disease progression and often have a poor prognosis. This article systematically summarizes the currently established criteria for biochemical response and analyzes the factors and underlying mechanisms associated with suboptimal UDCA response from multiple perspectives including genetic background， demographic factors， immunological features， and the gut-liver axis. Furthermore， it outlines the available second-line treatment drugs and emerging therapies， in order to provide a basis for early identification of high-risk patients and optimization of treatment strategies， as well as a reference for future research directions.
Primary biliary cholangitis （PBC） is an autoimmune-mediated chronic cholestatic liver disease. Ursodeoxycholic acid （UDCA） is the first-line treatment drug for PBC， yet some patients with suboptimal biochemical response to UDCA face a significant increase in the risk of disease progression and often have a poor prognosis. This article systematically summarizes the currently established criteria for biochemical response and analyzes the factors and underlying mechanisms associated with suboptimal UDCA response from multiple perspectives including genetic background， demographic factors， immunological features， and the gut-liver axis. Furthermore， it outlines the available second-line treatment drugs and emerging therapies， in order to provide a basis for early identification of high-risk patients and optimization of treatment strategies， as well as a reference for future research directions.
2026, 42(9): 2224-2228.
DOI: 10.12449/JCH260930
Abstract:
Liver fibrosis is a critical pathological stage in the progression of chronic liver diseases， involving the interaction between multiple mechanisms such as abnormal activation of hepatic stellate cells and extracellular matrix deposition. Since traditional animal models and two-dimensional cell culture systems cannot faithfully recapitulate the complex multicellular interactions and metabolic microenvironment of human liver fibrosis， three-dimensional liver organoid technologies have gradually been used in the construction of liver fibrosis models， providing novel research methods for mechanistic studies and therapeutic evaluation. Focusing on the construction of liver fibrosis-related organoid models， this article elaborates on the association of abnormal activation of hepatic stellate cells， chronic inflammatory response， gut-liver axis signaling， and lipid metabolic dysregulation with the progression of liver fibrosis and summarizes the current research advances in the application of organoid models for anti-fibrotic drug screening and targeted therapeutic assessment. Finally， this article briefly discusses the limitations of existing organoid models for liver fibrosis and future research directions， in order to provide a theoretical reference for both basic research and clinical application in liver fibrosis.
Liver fibrosis is a critical pathological stage in the progression of chronic liver diseases， involving the interaction between multiple mechanisms such as abnormal activation of hepatic stellate cells and extracellular matrix deposition. Since traditional animal models and two-dimensional cell culture systems cannot faithfully recapitulate the complex multicellular interactions and metabolic microenvironment of human liver fibrosis， three-dimensional liver organoid technologies have gradually been used in the construction of liver fibrosis models， providing novel research methods for mechanistic studies and therapeutic evaluation. Focusing on the construction of liver fibrosis-related organoid models， this article elaborates on the association of abnormal activation of hepatic stellate cells， chronic inflammatory response， gut-liver axis signaling， and lipid metabolic dysregulation with the progression of liver fibrosis and summarizes the current research advances in the application of organoid models for anti-fibrotic drug screening and targeted therapeutic assessment. Finally， this article briefly discusses the limitations of existing organoid models for liver fibrosis and future research directions， in order to provide a theoretical reference for both basic research and clinical application in liver fibrosis.
2026, 42(9): 2229-2235.
DOI: 10.12449/JCH260931
Abstract:
Metabolic reprogramming is a key characteristic of hepatocellular carcinoma， and abnormal fatty acid metabolism is closely associated with tumor immune escape. This article systematically reviews the molecular mechanisms of fatty acid metabolic reprogramming in hepatocellular carcinoma， focusing on key enzymes and their transcriptional regulatory networks within de novo lipogenesis and fatty acid oxidation pathways. This article also analyzes the metabolic heterogeneity between β-catenin-mutant hepatocellular carcinoma and AXIN1-mutant hepatocellular carcinoma and their therapeutic implications， summarizes the multidimensional mechanisms by which the lipid microenvironment regulates immune cell function， and reviews the targeted therapeutic strategies for different molecular subtypes of hepatocellular carcinoma.
Metabolic reprogramming is a key characteristic of hepatocellular carcinoma， and abnormal fatty acid metabolism is closely associated with tumor immune escape. This article systematically reviews the molecular mechanisms of fatty acid metabolic reprogramming in hepatocellular carcinoma， focusing on key enzymes and their transcriptional regulatory networks within de novo lipogenesis and fatty acid oxidation pathways. This article also analyzes the metabolic heterogeneity between β-catenin-mutant hepatocellular carcinoma and AXIN1-mutant hepatocellular carcinoma and their therapeutic implications， summarizes the multidimensional mechanisms by which the lipid microenvironment regulates immune cell function， and reviews the targeted therapeutic strategies for different molecular subtypes of hepatocellular carcinoma.
2026, 42(9): 2236-2241.
DOI: 10.12449/JCH260932
Abstract:
Liver transplantation is currently one of the most effective treatment methods for end-stage liver disease， and early postoperative mortality （typically defined as within 30 or 90 days after surgery） remains a key issue affecting the prognosis of patients. This article systematically reviews the research advances in early mortality following liver transplantation， elaborates on the definition， incidence rate， and clinical significance of early mortality， and discusses related risk factors from multiple dimensions， including donor factors， the preoperative status of the recipient， surgical techniques， postoperative complications， and immunosuppressive management. Furthermore， it analyzes the development and application of risk prediction models based on machine learning and big data in recent years and compares the predictive efficacy of different models. Meanwhile， this article summarizes the limitations of existing studies and explores future research directions， so as to provide a theoretical basis for the early identification of high-risk patients and the optimization of intervention strategies to reduce early mortality rates in clinical practice.
Liver transplantation is currently one of the most effective treatment methods for end-stage liver disease， and early postoperative mortality （typically defined as within 30 or 90 days after surgery） remains a key issue affecting the prognosis of patients. This article systematically reviews the research advances in early mortality following liver transplantation， elaborates on the definition， incidence rate， and clinical significance of early mortality， and discusses related risk factors from multiple dimensions， including donor factors， the preoperative status of the recipient， surgical techniques， postoperative complications， and immunosuppressive management. Furthermore， it analyzes the development and application of risk prediction models based on machine learning and big data in recent years and compares the predictive efficacy of different models. Meanwhile， this article summarizes the limitations of existing studies and explores future research directions， so as to provide a theoretical basis for the early identification of high-risk patients and the optimization of intervention strategies to reduce early mortality rates in clinical practice.
2026, 42(9): 2242-2250.
DOI: 10.12449/JCH260933
Abstract:
Immune rejection following liver transplantation is a critical factor affecting long-term graft survival. While traditional immunosuppressive regimens based on calcineurin inhibitors are effective， they are often accompanied by long-term side effects， making the induction of immune tolerance an important goal. This article systematically reviews the mechanisms of immune rejection following liver transplantation and the limitations of current drugs， with a focus on the potential of mesenchymal stem cells （MSCs） as a novel strategy for inducing immune tolerance. Preliminary clinical trials have confirmed that MSC infusion has a favorable safety profile and shows an immunomodulatory effect； however， there are still multiple challenges regarding the timing of infusion， cell source， dosage， and synergy with conventional regimens. Large-scale clinical trials are needed in the future to further validate their long-term efficacy and safety， and MSC therapy is expected to become a new direction for immune management in liver transplantation.
Immune rejection following liver transplantation is a critical factor affecting long-term graft survival. While traditional immunosuppressive regimens based on calcineurin inhibitors are effective， they are often accompanied by long-term side effects， making the induction of immune tolerance an important goal. This article systematically reviews the mechanisms of immune rejection following liver transplantation and the limitations of current drugs， with a focus on the potential of mesenchymal stem cells （MSCs） as a novel strategy for inducing immune tolerance. Preliminary clinical trials have confirmed that MSC infusion has a favorable safety profile and shows an immunomodulatory effect； however， there are still multiple challenges regarding the timing of infusion， cell source， dosage， and synergy with conventional regimens. Large-scale clinical trials are needed in the future to further validate their long-term efficacy and safety， and MSC therapy is expected to become a new direction for immune management in liver transplantation.
2026, 42(9): 2251-2256.
DOI: 10.12449/JCH260934
Abstract:
Pancreatic ductal adenocarcinoma （PDAC） has an extremely poor prognosis， and resistance to gemcitabine is one of the key reasons for treatment failure， with an underlying mechanism closely associated with lipid metabolic reprogramming in tumor cells. This article aims to systematically elaborate on the multidimensional drug resistance network constructed by such reprogramming and the feasibility of targeted intervention. Lipid metabolic reprogramming comprehensively remodels the metabolic homeostasis of PDAC cells by enhancing lipid uptake， de novo synthesis， storage， and oxidative catabolism in a synergistic manner. This process alters membrane lipid composition to impede drug influx and promote efflux， thereby reducing intracellular drug concentration. Meanwhile， it activates pathways involving sterol regulatory element-binding protein and peroxisome proliferator-activated receptor δ， couples lipid synthesis with cell survival， stemness， and anti-apoptotic capacity， and synergizes with autophagy to provide survival support through “lipophagy”. In addition， it reshapes the tumor microenvironment through “lipid hijacking” and the secretion of immunosuppressive mediators. Based on the above mechanisms， targeting key lipid metabolic enzymes （such as fatty acid synthase， stearoyl-CoA desaturase， carnitine palmitoyltransferase 1） or their upstream regulators has shown certain potential in reversing such drug resistance in preclinical studies. Although clinical translation faces the challenges such as systemic toxicity， metabolic redundancy in tumors， and patient heterogeneity， the development of biomarkers， intelligent drug delivery systems， and combined therapies may provide new ideas for overcoming drug resistance.
Pancreatic ductal adenocarcinoma （PDAC） has an extremely poor prognosis， and resistance to gemcitabine is one of the key reasons for treatment failure， with an underlying mechanism closely associated with lipid metabolic reprogramming in tumor cells. This article aims to systematically elaborate on the multidimensional drug resistance network constructed by such reprogramming and the feasibility of targeted intervention. Lipid metabolic reprogramming comprehensively remodels the metabolic homeostasis of PDAC cells by enhancing lipid uptake， de novo synthesis， storage， and oxidative catabolism in a synergistic manner. This process alters membrane lipid composition to impede drug influx and promote efflux， thereby reducing intracellular drug concentration. Meanwhile， it activates pathways involving sterol regulatory element-binding protein and peroxisome proliferator-activated receptor δ， couples lipid synthesis with cell survival， stemness， and anti-apoptotic capacity， and synergizes with autophagy to provide survival support through “lipophagy”. In addition， it reshapes the tumor microenvironment through “lipid hijacking” and the secretion of immunosuppressive mediators. Based on the above mechanisms， targeting key lipid metabolic enzymes （such as fatty acid synthase， stearoyl-CoA desaturase， carnitine palmitoyltransferase 1） or their upstream regulators has shown certain potential in reversing such drug resistance in preclinical studies. Although clinical translation faces the challenges such as systemic toxicity， metabolic redundancy in tumors， and patient heterogeneity， the development of biomarkers， intelligent drug delivery systems， and combined therapies may provide new ideas for overcoming drug resistance.
2026, 42(9): 2005-2005.
DOI: 10.12449/JCH2609.gwqkjpwzjj1
Abstract:
Hepatology｜Hepatocyte hnRNPK preserves mitochondrial integrity to restrain liver injury and fibrosis
2026, 42(9): 2021-2021.
DOI: 10.12449/JCH2609.gwqkjpwzjj2
Abstract:
2026, 42(9): 2175-2175.
DOI: 10.12449/JCH2609.gwqkjpwzjj3
Abstract:
2026, 42(9): 2066-2066.
DOI: 10.12449/JCH2609.zhixie
Abstract:
2015, 31(12): 1941-1960.
doi: 10.3969/j.issn.1001-5256.2015.12.002
Abstract:
2019, 35(12): 2706-2711.
doi: 10.3969/j.issn.1001-5256.2019.12.013
Abstract:
2011, 27(1): 113-128.
Abstract:
2011, 27(1): 110-112.
Abstract:
2018, 34(10): 2109-2120.
doi: 10.3969/j.issn.1001-5256.2018.10.011
Abstract:
2015, 31(12): 1980-1988.
doi: 10.3969/j.issn.1001-5256.2015.12.004
Abstract:
2017, 33(8): 1419-1431.
doi: 10.3969/j.issn.1001-5256.2017.08.003
Abstract:
2016, 32(1): 9-22.
doi: 10.3969/j.issn.1001-5256.2016.01.002
Abstract:
2019, 35(12): 2648-2669.
doi: 10.3969/j.issn.1001-5256.2019.12.007
Abstract:
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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
- 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)
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