Zhonghua Gan Zang Bing Za Zhi [JOURNAL]
Sun
200 papers
[Excerpt from the 2025 EASL practice guidelines for the diagnosis and treatment of extrahepatic cholangiocarcinoma].
Shang YW, Han GH
Zhonghua Gan Zang Bing Za Zhi · 2026 May · PMID 42209160 · Full text
In recent years, significant progress has been made in the imaging, molecular characterization, and systemic treatment of extrahepatic cholangiocarcinoma (CCA). However, early-stage detection, accurate classification, an...
In recent years, significant progress has been made in the imaging, molecular characterization, and systemic treatment of extrahepatic cholangiocarcinoma (CCA). However, early-stage detection, accurate classification, and effective management of CCA possess challenges. Therefore, the EASL commissioned an expert panel to draft evidence-based recommendations on account of recent research advances and significant differences in CCA subtypes for the management of extrahepatic CCA, including distal and perihilar CCA, with particular attention to the integration of emerging molecular concepts and practical strategies that reflect an accurate classification system needed in real-world clinical situations for the diagnosis and treatment.
[Expert recommendations on the management of adverse reactions in pegylated interferon alpha therapy for chronic hepatitis B].
Expert Group on the Management of Adverse Reactions in Pegylated Interferon Alpha Therapy for Chronic Hepatitis B
Zhonghua Gan Zang Bing Za Zhi · 2026 May · PMID 42209159 · Full text
To provide a usage reference for clinicians with the increasing use of pegylated interferon alpha (PEG-IFN-ɑ) in treating chronic hepatitis B (CHB), the expert panel retrospectively summarized previous clinical experienc...
To provide a usage reference for clinicians with the increasing use of pegylated interferon alpha (PEG-IFN-ɑ) in treating chronic hepatitis B (CHB), the expert panel retrospectively summarized previous clinical experience and formulated expert recommendations based on the latest research findings and evidence-based medical data of this field, focusing on pre-treatment assessment to better assist clinicians in managing adverse reactions, help patients complete treatment courses, and maximize patient benefits.
[Expert consensus on the clinical diagnosis and treatment of coagulation disorders related to liver disease].
National Clinical Research Center for Infectious Diseases, Society of Hepatology, Beijing Medical Association … +1 more , Translational Medicine Branch, Chinese Association of Gerontology and Geriatrics
Zhonghua Gan Zang Bing Za Zhi · 2026 May · PMID 42209158 · Full text
Coagulation disorders are a major contributing factor to bleeding and thrombotic diseases in patients with liver disease. Furthermore, it is one of the severe complications, which is closely related to disease progressio...
Coagulation disorders are a major contributing factor to bleeding and thrombotic diseases in patients with liver disease. Furthermore, it is one of the severe complications, which is closely related to disease progression and poor prognosis, affecting various diagnostic and therapeutic procedures in patients with liver disease. Therefore, accurately assessing the coagulation function, maintaining the balance of their coagulation status, and establishing clinical diagnostic and treatment standards for the prevention and treatment of bleeding and thrombosis are of great significance for the liver disease patients' clinical diagnosis and treatment. This consensus is formulated in discussion with experts from fields in hepatology, hematology, critical care medicine, laboratory medicine, and clinical pharmacy in reference to the latest evidence-based medicine with the aim of providing guidance for the clinical diagnosis and treatment of coagulation disorder in patients with liver disease.
[Key epidemiological data and recommended prevention and control measures for primary liver cancer].
Cao GW
Zhonghua Gan Zang Bing Za Zhi · 2026 May · PMID 42209157 · Full text
Primary liver cancer (PLC) accounted for 865,000 new cases worldwide in 2022, ranking sixth among all malignant tumors in terms of incidence, and 758,000 deaths, ranking third in mortality. The age-standardized 5-year su...
Primary liver cancer (PLC) accounted for 865,000 new cases worldwide in 2022, ranking sixth among all malignant tumors in terms of incidence, and 758,000 deaths, ranking third in mortality. The age-standardized 5-year survival rate for PLC in China has remained between 9.8% and 12.1%. Unlike other malignant tumors in China, the age-adjusted mortality rate of PLC in the middle-aged population (40-65 years) has consistently been higher than that in the elderly population aged 65 and above. Globally, hepatocellular carcinoma (HCC) accounted for 79.2% of PLC incidence and 78.8% of PLC mortality, with a male-to-female ratio of 3.3:1. The HCC incidence and mortality accounted for 45.2% and 44.6% of the world's totals, respectively, in China. There are three main categories of preventable risk factors for HCC: chronic persistent infections [hepatitis B virus (HBV), hepatitis C virus, and Clonorchis sinensis), metabolic factors (fatty liver disease, obesity, and type II diabetes), and behavioral/toxic factors (excessive alcohol consumption, smoking, and aflatoxin B1).The population attributable fraction (PAF) of these three categories of nine controllable risk factors for global HCC was 78.4%. Among them, HBV contributed the most to HCC etiology worldwide, with a PAF of 57.1%. HBV is the most important cause of all HCC in China, with HBV-positivity accounting for 84.4% and the PAF being 76.1%. Metabolic factors among the three major risk factors are growing steadily worldwide. Theoretically, functional cure of HBV, prevention and treatment of related chronic infections, reduction of metabolic diseases through aerobic exercise and dietary management, and control of tobacco, alcohol, and toxin exposure could prevent 78.4% of global HCC occurrence. Defining high-risk populations using indicators such as liver function and cirrhosis status, along with HCC screening and proactive prevention, offers a suitable input and output ratio for implementing primary prevention based on HBV replication and evolution. Models based on serum alpha-fetoprotein-3 and prothrombin can effectively enable secondary prevention through HCC screening, diagnosis, and treatment, improving patient survival rates at early stages. Targeted therapy and immunotherapy can downstage the disease, creating opportunities for surgical resection to achieve tertiary prevention for intermediate-to-advanced-stage HCC. Comprehensive management is required, with a focus on intervening and controlling the nine major risk factors to prevent PLC occurrence.
[Research advances on hepatocyte zonal changes in metabolic associated fatty liver disease].
Li Y, Huang ZW, Gan JT … +2 more , Zhang QF, Fu WW
Zhonghua Gan Zang Bing Za Zhi · 2026 Apr · PMID 42036238 · Full text
Hepatocyte zonation is a core feature of the spatial heterogeneity of liver function, which is driven by the process of gradients of oxygen and nutrients from the portal vein to the central vein and is precisely regulate...
Hepatocyte zonation is a core feature of the spatial heterogeneity of liver function, which is driven by the process of gradients of oxygen and nutrients from the portal vein to the central vein and is precisely regulated by signaling pathways such as Wnt/β-catenin, thereby forming distinct metabolic functional zones. This zonation mechanism is crucial to preserving hepatic metabolic homeostasis. However, zonation stability is disrupted in metabolic associated fatty liver disease (MAFLD). The pericentral venous zone (Zone 3) is the initial site of steatosis and oxidative stress due to lipid metabolism imbalance and hypoxic sensitivity, while the periportal venous zone (Zone 1) exhibits metabolic abnormalities associated with insulin resistance. Furthermore, the dissemination of inflammatory activation and fibrosis from Zone 3 to the entire lobule with zonation disruption facilitates disease progression. Therefore, an in-depth understanding of the hepatocyte zonation mechanism is of enormous significance for revealing the pathogenesis, pathological evolution, and treatment strategies of MAFLD. This article systematically explains that the homeostasis of hepatocyte zonation is fundamental to maintaining a healthy liver, whereas zonation disorders are a central factor driving MAFLD progression, providing a theoretical basis for understanding pathogenesis from a spatial metabolism perspective and exploring new therapeutic strategies based on recent research findings.
[Research progress on poor response, resistance mechanisms, and influencing factors of immunotherapy for hepatocellular carcinoma].
Huang M, Zhang FN, Gong H … +3 more , Liu CC, Zhao TT, He N
Zhonghua Gan Zang Bing Za Zhi · 2026 Apr · PMID 42036237 · Full text
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although immune checkpoint inhibitors offer hope for patients with advanced- stage HCC, the objective response rate remains...
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although immune checkpoint inhibitors offer hope for patients with advanced- stage HCC, the objective response rate remains only 15% to 30%, mainly due to primary or secondary drug resistance. This article systematically reviews the potential mechanisms and influencing factors of poor immunotherapy responses in HCC, aiming to provide theoretical reference for an in-depth understanding of primary non-response, secondary drug resistance, or immunotherapy resistance and the development of personalized treatment strategies.
[Advances in the application of exhaled breath analysis technology in the detection and diagnosis of liver failure].
Zhang ST, Liu YS, He YL
Zhonghua Gan Zang Bing Za Zhi · 2026 Apr · PMID 42036236 · Full text
In recent years, exhaled breath analysis technology has shown significant potential for the detection and diagnosis of liver diseases as an innovative noninvasive diagnostic method. This paper systematically reviews the...
In recent years, exhaled breath analysis technology has shown significant potential for the detection and diagnosis of liver diseases as an innovative noninvasive diagnostic method. This paper systematically reviews the recent relevant literature on the application progress of exhaled breath analysis in the field of liver failure at home and abroad, including the correlation between volatile organic compounds and liver pathology, the principles and advantages and disadvantages of present mainstream technologies (mass spectrometry, electronic nose, and spectroscopy analysis), the development and application in warning early-stage conditions and prognostic assessment following treatment, as well as the facing challenges and future application status.
[Research progress on the effects of time-restricted eating on metabolic associated fatty liver disease].
Jiang ZQ, Wei TJ, Li GX
Zhonghua Gan Zang Bing Za Zhi · 2026 Apr · PMID 42036235 · Full text
Metabolic-associated fatty liver disease (MAFLD) is a common chronic liver disease closely related to metabolic disorders. Currently, the effective pharmacological treatments are scarce. In recent years, time-restricted...
Metabolic-associated fatty liver disease (MAFLD) is a common chronic liver disease closely related to metabolic disorders. Currently, the effective pharmacological treatments are scarce. In recent years, time-restricted eating (TRE), as an emerging dietary intervention strategy, has been shown in studies to have significant preventive and therapeutic potential for diseases related to metabolic dysfunction. However, the effects of TRE on MAFLD and the underlying mechanisms remain not fully elucidated. This review briefly summarizes the present research progress of this field in terms of the effects, improvement, and mechanistic role of TRE on MAFLD.
[Research advances of magnetic resonance elastography for assessing the bioinvasiveness in hepatocellular carcinoma].
Ma MY, Li RK
Zhonghua Gan Zang Bing Za Zhi · 2026 Apr · PMID 42036234 · Full text
The invasiveness of hepatocellular carcinoma (HCC) is closely correlated with the dynamic changes in the biomechanical microenvironment. The solid (e.g., tissue sclerosis due to stromal fibrosis) and fluid mechanics proc...
The invasiveness of hepatocellular carcinoma (HCC) is closely correlated with the dynamic changes in the biomechanical microenvironment. The solid (e.g., tissue sclerosis due to stromal fibrosis) and fluid mechanics processes (e.g., disordered interstitial hydraulic gradient) of HCC are significantly aberrant in comparison to normal liver tissue. These mechanical characteristics synergistically promote tumor invasion and metastasis by regulating mechanosensitive pathways and forming an interaction network with key biochemical signals. Magnetic resonance elastography (MRE), as a non-invasive technique, enables quantitative assessment of the mechanical heterogeneity of HCC by accurately characterizing tissue viscoelastic indices (e.g., shear modulus and loss modulus). Several studies have confirmed that MRE parameters are strongly correlated with tumor differentiation grade, microvascular invasion status, and molecular phenotypes (e.g., high Ki-67 expression and phosphatidylinositol proteoglycan 3 targeting). Furthermore, MRE's quantitative assessment of tumor hardness can provide objective support for prognostic stratification by accurately predicting the likelihood of postoperative recurrence. The non-invasive, reproducible, and quantitative advantages of MRE, which are based on the invasive assessment of HCC, demonstrate its unique clinical value. Multidimensional information in support of conventional imaging and molecular marker evaluation facilitates the early-stage diagnosis, personalized treatment, and dynamic monitoring of HCC.
[Global differences and challenges in the definition of acute liver failure].
Ren Y, Kong M, Xu MM … +1 more , Chen Y
Zhonghua Gan Zang Bing Za Zhi · 2026 Apr · PMID 42036233 · Full text
Acute liver failure (ALF) is a critical syndrome characterized by sudden deterioration of liver function, coagulopathy, and hepatic encephalopathy, with a very high mortality rate. However, the global ALF diagnostic crit...
Acute liver failure (ALF) is a critical syndrome characterized by sudden deterioration of liver function, coagulopathy, and hepatic encephalopathy, with a very high mortality rate. However, the global ALF diagnostic criteria exhibit significant heterogeneity, with remarkable differences among countries in terms of disease course duration, grading requirements for hepatic encephalopathy, exclusion principles for basic liver disease, and accompanied symptoms. This inconsistency hinders accurate determination of liver transplantation timing, epidemiological comparisons, prognostic assessments, and cross-border research. This article systematically analyzes the core differences in ALF definitions among liver disease-related associations in China, Japan, Europe, and America; explores their impact on clinical practice and scientific research; and proposes strategies such as multicenter collaboration and molecular typing to promote global integration and research advancement for ALF definitions.
[A real-world study of clinical cure in children with HBeAg-positive chronic hepatitis B from the Guangxi region].
Lyu RY, Tian JH, Huang SM … +5 more , Meng ML, Xiang WY, Fan PY, Li J, Li SX
Zhonghua Gan Zang Bing Za Zhi · 2026 Apr · PMID 42036232 · Full text
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[Clinical characteristics and follow-up in children with Alagille syndrome].
Liu WW, Zhong XM, Wang P … +4 more , Wang MJ, Jin M, Zhang R, Mi MR
Zhonghua Gan Zang Bing Za Zhi · 2026 Apr · PMID 42036231 · Full text
To investigate the clinical and genetic features and follow-up outcomes in children with Alagille syndrome (ALGS). A retrospective cohort study was conducted. Clinical data from 24 children diagnosed with ALGS treated a...
To investigate the clinical and genetic features and follow-up outcomes in children with Alagille syndrome (ALGS). A retrospective cohort study was conducted. Clinical data from 24 children diagnosed with ALGS treated at Capital Children's Medical Center, Capital Medical University, from January 2015 to January 2025 were collected and analyzed. Genetic variation characteristics were collected by comparing biochemical indicator changes in children who were followed up for over six months before and after treatment. Independent samples -tests or rank-sum tests were used to compare continuous data between groups. The correlation between liver stiffness and bile acid levels was compared using Spearman correlation analysis. Out of the 24 enrolled cases, ten were male. The occurrence rate during the neonatal phase accounted for 62.5% (15/24), while the occurrence rate before six months of age was 87.5% (21/24). The median age at the time of confirmed diagnosis was 16 months (26 days, 11 years). The common clinical manifestations were cholestasis, accounting for 87.5% (21/24); hepatomegaly, 75.0% (18/24); distinctive facial features, 70.8% (17/24); and butterfly-shaped vertebrae, 45.8% (11/24). Cardiovascular involvement accounted for 45.8% (11/24). Growth and development retardation was observed in 37.5% (9/24). The pruritus incidence rate at the time of definite diagnosis in pediatric patients was 54.2% (13/24). Among the five pediatric patients who underwent liver biopsy, three had the typical pathology of intrahepatic bile duct insufficiency. Genetic examinations were performed in all 24 cases. The gene mutation was present in 22 cases, while the gene mutation was present in two. Exon deletion was detected in one case, splicing variants in eight, frameshift variations in six, nonsense variations in three, and missense variations in six. Among ALGS cases, 21 patients survived following autologous liver transplantation and were followed up for at least six months. Aspartate aminotransferase, total bilirubin, direct bilirubin, γ-glutamyl transferase, triglycerides, and low-density lipoprotein cholesterol were significantly declined (<0.05). Serum cholesterol levels were increased during follow-up compared to the disease onset phase and showed a progressive trend with prolonged disease duration. Liver stiffness values exhibited an annual upward trend and correlated positively with bile acid levels. Cholestasis, hepatomegaly, distinctive facial features, and the presentation of early-stage liver fibrosis are common clinical manifestations during the ALGS diagnosis in pediatric patients. Certain liver disease indicators may improve following treatment, resulting in a substantial reduction in bilirubin levels; however, hypercholesterolemia may develop.
[Exploring the protective effects and mechanisms of HYX1-derived exosomes on acute liver failure based on disulfidptosis signaling].
Yang Q, Tang HX, Liu XX … +2 more , Chen Y, Bai L
Zhonghua Gan Zang Bing Za Zhi · 2026 Apr · PMID 42036230 · Full text
To explore the protective effect and molecular mechanism of human liver stem cell line HYX1-derived exosomes (HYX1-Exos) on acute liver failure (ALF) based on disulfidptosis signaling. Healthy male BALB/c mice were intr...
To explore the protective effect and molecular mechanism of human liver stem cell line HYX1-derived exosomes (HYX1-Exos) on acute liver failure (ALF) based on disulfidptosis signaling. Healthy male BALB/c mice were intraperitoneally injected with D-galactosamine/lipopolysaccharide (D-GalN/LPS) to induce ALF. Mice were divided into a normal control group, an acute liver failure group (ALF group), a disulfidptosis inhibitor tris (2-carboxyethyl) phosphine (TCEP) intervention group (TCEP+ALF group), a HYX1-Exos intervention group (HYX1-Exos+ALF group), and a SLC7A11-IN-1 intervention group (SLC7A11-IN-1+ALF group), with five mice per group. Blood and liver tissue samples were collected. The degree of liver tissue damage was assessed based on serum transaminase levels and hematoxylin-eosin staining results. Quantitative PCR was used to analyze the gene expression levels of disulfidptosis markers SLC7A11, GLUT1, and WAVE2 in liver tissues of each group. Cell Counting Kit-8 (CCK-8) was used to evaluate hepatocyte viability. Statistical analysis was performed using the independent samples -test and one-way ANOVA. TCEP treatment had significantly alleviated liver damage in ALF mice, as indicated by a marked reduction in transaminase levels [alanine aminotransferase: (312.01±19.46) U/L . (1 512.09±229.34) U/L, =10.38, <0.001; aspartate aminotransferase: (76.30±39.63) U/L . (324.17±78.27) U/L, =5.75, <0.001] and a notable improvement in liver histology. HYX1-Exos treatment had significantly reduced liver injury and disulfidptosis levels in ALF mice. Liver injury and disulfidptosis levels were significantly reduced with inhibition of SLC7A11 in ALF mice. experiments showed that HYX1-Exos protected hepatocytes from disulfidptosis induced by high SLC7A11 under glucose starvation. Disulfidptosis plays an important role in the development of ALF, and HYX1-Exos likely have a hepatoprotective effect on ALF by inhibiting SLC7A11-mediated disulfidptosis.
[Study on the establishment, assessment, and drug sensitivity testing for intrahepatic cholangiocarcinoma organoid models based on the suspension culture method].
Su YH, Huang W, Yu C … +6 more , Liu YR, Wu PR, Chai CP, Li L, Xu H, Zhou WC
Zhonghua Gan Zang Bing Za Zhi · 2026 Apr · PMID 42036229 · Full text
To investigate the feasibility of establishing intrahepatic cholangiocarcinoma (ICC) organoid models based on the suspension culture method. Fresh tumor tissue specimens were prepared from six patients with intrahepatic...
To investigate the feasibility of establishing intrahepatic cholangiocarcinoma (ICC) organoid models based on the suspension culture method. Fresh tumor tissue specimens were prepared from six patients with intrahepatic cholangiocarcinoma using digestive enzymes for a cell suspension. The cells were cultured as organoids in ultra-low attachment plates. Passaging and cryopreservation were used once the organoids reached an appropriate size. The formation of the organoids was monitored and recorded using an inverted microscope during the culture process. The organoids were collected and detected by hematoxylin-eosin staining and immunohistochemistry. The protein expressional conditions were examined. Stable passaged and cryopreserved organoids from three tumor tissue samples were successfully constructed. Hematoxylin-eosin staining results showed that the organoids were structurally similar to the primary tissue. Immunohistochemical staining results demonstrated that CK7, CK19, E-cadherin, and vimentin were all positively expressed, with Ki67 positivity rates of approximately 50%, 30%, and 80%, respectively. The suspension culture method can construct organoid models in terms of tissue structure and protein expression that exhibit tumor characteristics of intrahepatic cholangiocarcinoma.
[Diagnostic value and clinical significance of matrix metalloproteinase-7, gamma-glutamate transferase, and liver stiffness measurement with ultrasound elastography in children with biliary atresia].
Zhang JM, Sun YL, Li QZ … +6 more , Peng YY, Qin D, Liu QJ, Fan C, Wang YM, Zhu L
Zhonghua Gan Zang Bing Za Zhi · 2026 Apr · PMID 42036228 · Full text
To investigate the diagnostic value and clinical significance of matrix metalloproteinase-7 (MMP-7), gamma-glutamyl transferase (GGT), and liver stiffness measurement (LSM) with ultrasound elastography in children with b...
To investigate the diagnostic value and clinical significance of matrix metalloproteinase-7 (MMP-7), gamma-glutamyl transferase (GGT), and liver stiffness measurement (LSM) with ultrasound elastography in children with biliary atresia (BA). A retrospective study was conducted. Forty-five children diagnosed with cholestasis at the Guiyang Maternal and Child Health Hospital between January 2022 and February 2025 were selected as the study subjects. All subjects underwent clinical examination. Pre-enrollment diagnoses were thoroughly documented. The children were divided into a BA group (=20) and a non-BA group (=25) based on intraoperative cholangiography and follow-up results. The levels of MMP-7, GGT, direct bilirubin (DBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, total bile acids, and LSM were compared between the two groups. Indicators with statistically significant differences were used to plot and calculate receiver operating characteristic (ROC) curves. The model's stability was internally validated by the bootstrap method. Continuous variables were compared using -tests or rank-sum tests. Categorical variables were analyzed using tests. The highest observed effect size among all indicators, matrix metalloproteinase-7 (effect size ≈2.5), with an α error probability set at 0.05 was determined using the G*Power 3.1 software. The statistical reliability of the present sample size (BA group =20, non-BA group =25) was analyzed using the efficacy calculation model of the Mann-Whitney U test (two independent samples). The levels of MMP-7 [38.95 (17.50, 58.75) μg/L . 6.00 (6.00, 7.00) μg/L], GGT [492.04 (237.92, 611.25) U/L . 166.00 (86.95, 220.00) U/L], DBil [139.16 (122.62, 164.45) µmol/L . 100.90 (62.90, 149.90) µmol/L], and LSM [12.0 (10.0, 17.5) kPa . 7.0 (6.0, 8.0) kPa] were significantly higher in the BA group than those in the non-BA group, and the differences were statistically significant (<0.05). MMP-7 as a single indicator demonstrated extremely high diagnostic efficacy in BA diagnosis, with an area under the ROC curve of 0.987. Combining MMP-7 with DBil and LSM further enhanced diagnostic efficacy, achieving a combined AUC of 0.990. The bootstrap method had validated the model as stable and reliable. The statistical power analysis indicated that with the present study sample size, key diagnostic indicators, such as MMP-7, were >0.99. MMP-7, GGT, DBil, and LSM have significant value in the diagnosis of BA. Among them, MMP-7 serves as an independent biomarker with the highest diagnostic efficacy, while combining it with LSM and DBil further improves diagnostic efficacy.
[ATPase H transporter expression with prognosis in hepatocellular carcinoma].
Yuan Q, Jin YQ, Cao YX … +4 more , Cheng LJ, Fan HM, Liu Y, Yang L
Zhonghua Gan Zang Bing Za Zhi · 2026 Apr · PMID 42036227 · Full text
To investigate the expression level of ATPase H transporting accessory protein 1 (ATP6AP1) in hepatocellular carcinoma (HCC) lines and its effect on cell proliferation and migration, providing a new target for the treatm...
To investigate the expression level of ATPase H transporting accessory protein 1 (ATP6AP1) in hepatocellular carcinoma (HCC) lines and its effect on cell proliferation and migration, providing a new target for the treatment of HCC. Real-time quantitative polymerase chain reaction (RT-PCR) was used to detect the differential expression of ATP6AP1 in normal hepatocyte line L02 and hepatocellular carcinoma line HepG2. An ATP6AP1 knockdown group (KD group) and a negative control group (NC group) were constructed by lentiviral infection. The proliferation and migration abilities were detected by CCK8 cell proliferation and cell scratch assay between the two groups. Independent samples -test was used to analyze the differences between groups. Bioinformatics analysis was performed on the Cancer Genome Atlas (TCGA) databases using Kaplan-Meier Plotter, UALCAN, and GEPIA to explore the differential expression of ATP6AP1 in HCC patients and its impact on prognosis. Bioinformatics results showed that the expression level of ATP6AP1 was significantly higher in HCC tissues than that in normal liver tissues (<0.05). Functional enrichment analysis indicated that ATP6AP1 regulated lysosomal function, intracellular acidification, and the immune microenvironment in HCC progression. RT-PCR results showed that ATP6AP1 mRNA expression was significantly higher in HepG2 liver cancer cells than that in normal hepatocytes L02 (<0.05). The relative expression level of ATP6AP1 mRNA was significantly lower in the KD group (0.18±0.01) than that in the NC group (1.00±0.08) (<0.001). CCK assays showed that the profileration capacity was significantly higher in KD group than that in the NC group from day 3 to day 5 (<0.05), with a significant time-effect relationship (<0.001). Cell scratch assay results showed that the migration rate was significantly higher in the NC group than that of the KD group over time, with a slower scratch repair rate. High expression of ATP6AP1 plays a pro-cancerous role in HCC progression and may serve as a potential biomarker for predicting prognosis and a potential therapeutic target.Therefore, further validation of its mechanism of action in animal models and clinical samples is needed in the future.
[Interferon-α induces disulfidptosis occurrence in human liver cancer cells].
Bi XY, Zhang J, Xu LH … +3 more , Chu XR, Liu SS, Xin YN
Zhonghua Gan Zang Bing Za Zhi · 2026 Apr · PMID 42036226 · Full text
To investigate the potential molecular regulatory mechanism of interferon-α (IFN-α)-induced disulfidptosis occurrence in human liver cancer cells. Glucose starvation and IFN-α treatment models were constructed using hum...
To investigate the potential molecular regulatory mechanism of interferon-α (IFN-α)-induced disulfidptosis occurrence in human liver cancer cells. Glucose starvation and IFN-α treatment models were constructed using human hepatocellular carcinoma cell lines HepG2 and Huh7, respectively. Western blotting (WB), NADPH content measurement, and immunofluorescence staining were employed to evaluate disulfidptosis-related phenotypes, such as intracellular disulfide bond accumulation, NADPH depletion, and filamentous actin (F-actin) skeleton collapse. The reversibility of the phenotypes was validated by combining the disulfidptosis inhibitor D-penicillamine (D-Pen). The expression of solute carrier family 7 member 11 (SLC7A11) was downregulated using siRNA interference to evaluate the dependence of IFN-α-induced disulfidptosis on the SLC7A11 pathway. Furthermore, the GEO transcriptome dataset was employed to conduct differential gene analysis for screening candidate molecules involved in the regulation of IFN-α-induced disulfidptosis. Quantitative data are presented as mean ± standard deviation (SD). Comparisons between two groups were performed using the independent-samples test, while comparisons among multiple groups were analyzed by one-way analysis of variance (ANOVA), followed by Dunnett's t test for pairwise comparisons. Compared with the control group, glucose starvation and IFN-α treatment both induced disulfidptosis-related phenotypes in HepG2 and Huh7 cells, characterized by increased intracellular disulfide bond levels, decreased NADPH content, and F-actin cytoskeleton collapse. Following IFN-α treatment, the accumulation of high-molecular-weight protein aggregates increased in a time- and dose-dependent manner. Compared with IFN-α treatment alone, combined D-Pen intervention partially alleviated intracellular disulfide accumulation, NADPH depletion, and F-actin cytoskeletal collapse. Under conditions of SLC7A11 knockdown, IFN-α-induced high-molecular-weight protein aggregation was further aggravated, suggesting that regulatory mechanisms independent of SLC7A11 may also be involved in this process. Transcriptomic differential expression analysis revealed that β2-microglobulin (B2M), ubiquitin-specific peptidase 18 (USP18) and proteasome activator subunit 1 (PSME1) were upregulated following IFN-α stimulation, among which PSME1 also showed increased protein expression after IFN-α treatment. IFN-α can induce disulfidptosis-related phenotypic changes in HepG2 and Huh7 human hepatocellular carcinoma cells. The upregulation of B2M, USP18, and PSME1 suggests that these molecules may be involved in this process; however, the specific underlying mechanisms require further investigation.
[Precise clinical classification of metabolic associated fatty liver disease].
Su WR, Ding JJ, Pan Q … +1 more , Chai J
Zhonghua Gan Zang Bing Za Zhi · 2026 Apr · PMID 42036225 · Full text
Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide, and its significant clinical and pathophysiological heterogeneity poses a serious challenge to traditional "one-size-fi...
Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide, and its significant clinical and pathophysiological heterogeneity poses a serious challenge to traditional "one-size-fits-all" diagnostic and therapeutic approaches. Therefore, constructing a precise clinical classification system to identify patient subgroups with varying risks and treatment responses has become a core frontier in this field. This article systematically summarizes the main current MAFLD classification methods, covering content from simple classification based on clinical phenotypes (e.g., body mass index) to non-invasive risk stratification via serology and imaging markers, and further extending to deep molecular subtyping driven by cutting-edge multi-omics technologies and artificial intelligence. In addition, it analyzes and points out the limitations of single-dimensional classification approaches. The future development trend is to construct a multi-dimensional, dynamic assessment system that integrates clinical, non-invasive biomarkers and deep molecular features, providing a comprehensive framework for laying a scientific foundation for elucidating the origins of disease heterogeneity, achieving personalized risk assessment, precision-targeted interventions, and innovative clinical trial designs, ultimately propelling MAFLD into the era of precision medicine.
[Research progress on the mechanisms and optimization strategies of mesenchymal stem cell-derived exosomes in the treatment of liver diseases].
Li XR, Niu B, Zhang LY
Zhonghua Gan Zang Bing Za Zhi · 2026 Mar · PMID 41956794 · Full text
As an emergent acellular therapeutic tool, mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated good application prospects in the prevention and treatment of liver diseases. MSC-Exos exhibit a lower immuno...
As an emergent acellular therapeutic tool, mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated good application prospects in the prevention and treatment of liver diseases. MSC-Exos exhibit a lower immunogenicity and tumorigenic risk in comparison to traditional stem cell therapy and can also exert multiple therapeutic effects in liver diseases by carrying various active factors, including miRNAs and proteins, which play anti-inflammatory, anti-cell death, anti-fibrosis roles among others. In recent years, MSC-Exos have demonstrated effective therapeutic outcomes in different liver disease models, particularly receiving widespread attention in the field of acute and chronic liver injury and liver fibrosis. This article systematically reviews the mechanistic research of MSC-Exos and key variables influencing their efficacy in liver disease treatment, including exosome preparation techniques, tissue sources, drug administration plans, and delivery routes. Additionally, it focuses on discussing its functional optimization strategies, such as pretreatment, engineering modifications, and intelligent delivery systems, and explores the synergistic advantages of combined intervention with MSC-Exos and traditional Chinese and Western medicine. MSC-Exos is still considered a hot direction for achieving precise treatment of liver disease, although current research still faces challenges such as inconsistent standards and insufficient clinical evidence. In the future, it will be necessary to strengthen standardized production and clinical translation research to promote its clinical application in individualized interventions.
[Advances in the construction and application of a novel liver organoid model for hepatitis B virus infection].
Li H, Xiang KH
Zhonghua Gan Zang Bing Za Zhi · 2026 Mar · PMID 41956793 · Full text
Hepatitis B virus (HBV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma, posing a threat to human health, yet its specific pathogenic mechanisms have not been fully elucidated. Orga...
Hepatitis B virus (HBV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma, posing a threat to human health, yet its specific pathogenic mechanisms have not been fully elucidated. Organoid models have shown great potential in recent years due to significant limitations in existing cellular and animal models for HBV research. The construction of in vitro liver organoid models is important for better exploring HBV pathogenic mechanisms and achieving early-stage prevention and treatment. Currently, human liver organoid (HLO) models have been explored using various differentiation and culture protocols and have been confirmed to hold enormous potential in tissue development, disease model construction, personalized medicine, drug screening, and other aspects. This article briefly outlines the characteristics, differentiations, culture strategies, and applications of the emerging HLO model, thus providing a reference value for better understanding and optimizing support to HBV research.
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