中华肝脏病杂志最新文献

Objective: To evaluate the efficacy of the Baveno VI criteria in the diagnosis of clinically significant portal hypertension (CSPH) under two conditions: non-etiological control and complete etiological control. Methods: A cross-sectional study was conducted. Clinical data were collected from 232 cases with compensated advanced chronic liver disease who underwent hepatic venous pressure gradient measurement and had liver stiffness measurement (LSM) ≥10 kPa at Nanfang Hospital, Southern Medical University, between July 2019 and December 2024. Patients were categorized into the etiological control group (78 cases) and the non-etiological control group (154 cases) according to the definition of etiological control. Patients meeting the criteria for etiological control or near-control, with alanine transaminase≤upper limit of normal (ULN) were further defined into the near-etiological control group (110 cases). Intergroup comparisons of normally distributed and skewed quantitative data were performed using the independent sample t-test and the Mann-Whitney U test, respectively. Categorical variables were compared using χ² tests. The diagnostic performance of LSM in predicting CSPH under controlled and uncontrolled conditions was evaluated based on sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: The PPVs of LSM≥25 kPa for diagnosing CSPH in the overall population, the subgroups of the etiological-control, non-control, and nearly control were 82.8%, 93.3%, 79.6%, and 92.0%, respectively, with specificities of 89.3%, 96.3%, 86.8%, and 95.3%. The PPVs of LSM≥25 kPa for diagnosing CSPH were 90.0% and 76.9%, respectively, with the specificities of 93.8% and 85.0% in the non-control group with ALT≤ULN and ALT>ULN. LSM≥25 kPa demonstrated PPVs of 90.0% and 76.9% for diagnosing CSPH in populations with ALT≤ULN and ALT>ULN, respectively, with specificities of 93.8% and 85.0% in the non-etiological control group. The sensitivity and NPV for excluding CSPH using LSM≤15 kPa combined with platelet count (PLT)≥150×10⁹/L in the etiological-control group, the non-control group, and the near-control group were 100% in the overall population. The combined model of LSM≥25 kPa and LSM≤15 kPa+PLT ≥150×10⁹/L for diagnosing and excluding CSPH yielded gray zone rates of 60.3%, 67.9%, 56.5%, and 64.6% in the overall population and subgroups, respectively. The combined model of LSM≥25 kPa and LSM≤15 kPa+PLT≥110×10⁹/L yielded gray zone rates of 50.8%, 59.0%, 46.8%, and 58.2% in the overall population and subgroups, respectively. Conclusion: The Baveno VI criteria reliably and effectively identify CSPH in patients with cACLD with well-controlled etiologies but remain to be validated in the non-controlled etiology group.

Objective: To analyze the antiviral efficacy and its influencing factors in pediatric patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). Methods: Thirty-eight initially treated pediatric patients with HBeAg-negative CHB who visited the Department of Hepatology of the Fifth Medical Center of the General Hospital of the People's Liberation Army (PLA) from June 2010 to June 2019 were retrospectively enrolled, and the clinical medications included interferon alpha (IFN-α) and nucleos(t)ide analogs (NAs). The antiviral efficacy and safety profile were assessed at 96 weeks. Pediatric patients were categorized into a cure group [quantitative HBsAg (qHBsAg)<0.05 IU/mL], a low HBsAg group (0.05 IU/mL≤qHBsAg ≤ 1 500.00 IU/mL), and a high HBsAg group (qHBsAg>1 500.00 IU/ mL) according to different levels of hepatitis B surface antigen (HBsAg). The antiviral efficacy and its influencing factors were analyzed using the Kaplan-Meier method and generalized estimating equations in pediatric patients. Results: Clinical cure was achieved in 13% (5/38) at 96 weeks in pediatric patients. Young age at baseline and high B-lymphocyte count levels were the characteristics of pediatric patients who achieved clinical cure. Further analysis indicated that the HBsAg-negative conversion rate was significantly higher in children aged 1-<3 years than that in children aged 3-<7 and 7-12 years [33% (4/12), 5% (1/20), and 0 (0/6) in the three groups, respectively, P=0.025]. No serious adverse reactions were observed during treatment and follow-up. Conclusion: Antiviral therapy efficacy and safety profile are superior for HBeAg-negative CHB children, and some children can achieve clinical cure.Younger age at baseline and higher B-lymphocyte count level might be important factors favoring the clinical cure in children.

Objective: This study systematically assessed the latest epidemiological model and changing trends of metabolic-associated fatty liver disease (MAFLD)-associated cirrhosis at the global and regional levels based on the updated 2021 Global Burden of Disease (GBD2021) database, with the aim to provide important reference to make decisions in patients. Methods: Global and regional data on MAFLD-associated cirrhosis were extracted from the GBD 2021 database. Prevalence, incidence rate, and total years lived with disability (YLD), as well as age-standardized rates per 100 000 population, were analyzed according to year, age, and gender. Estimated results were presented with uncertainty intervals (UIs) to ensure the robustness of the statistical findings. Results: The global age-standardized prevalence of MAFLD-associated cirrhosis was 15,017.5 (95% UI 13 755.8-16 360.8) per 100 000 population, the incidence rate was 876.5 (95% UI 862.2-890.0) per 100 000 population, and the YLD rate was 0.4 (95% UI 0.2-0.6) per 100 000 population in 2021. The highest age-standardized prevalence was observed in North Africa and the Middle East, Central Latin America, and Tropical Latin America among the regions. The lowest age-standardized prevalence was observed in high-income North America, Australia, and high-income Asia-Pacific. The highest age-standardized prevalence was observed in Kuwait, Egypt, and Qatar, while the lowest was observed in Japan, Finland, and Canada among 204 countries. Gender analysis revealed that the prevalence rate was significantly higher in males than females, with a peaked prevalence rate in the 45-49 age group for males and the 50-54 age group for females. The incidence rates peaked in the 15-19 and 20-24 age groups, respectively. Conclusion: MAFLD-associated cirrhosis is a global health problem. The highest incidence rates are found in North Africa and the Middle East, central Latin America, and southern sub-Saharan Africa, while the lowest rates are found in high-income North America, Australia, and the Asia-Pacific region. The prevalence, incidence, and YLD and their corresponding age-standardized rates were higher in males than in females between 2010 and 2021. Therefore, understanding the epidemiological characteristics and evolving trends will aid in formulating preventive and treatment strategies to reduce the global burden of MAFLD-associated cirrhosis.

Artificial intelligence (AI) has shown great potential in the field of hepatology, and it is gradually revolutionizing novel research for liver diseases. However, its full integration into real-world diagnostic and treatment processes still faces significant challenges. This article analyzed the application progress of AI in key areas such as big data analysis, translational research, and imaging and pathological interpretation. Physicians need to integrate massive amounts of multimodal data (medical history, physical signs, laboratory data, imaging, and pathology) to make informed decisions in clinical practice. Although AI has gradually shown a preliminary auxiliary application role in certain liver disease diagnosis and treatment scenarios, current machine learning and deep learning technologies are far from being able to effectively support clinical decision-making in real-world settings. The core pain points are as follows: firstly, AI tools are not yet mature enough to truly independently and reliably assist in complex clinical evaluation; secondly, even if assistance is provided, the ultimate responsibility for medical decisions still clearly belongs to the physician, failing to reduce their workload effectively; finally, due to the different specialties and data characteristics of various medical centers, individually trained AI models are often relatively independent and personalized, fragmented, and difficult to integrate into a widely applicable and scalable multi-center general model, limiting their universal value. In the future, enhancing clinicians' understanding of AI and building multidisciplinary collaborative networks will be crucial to accelerating the development of AI-driven decision support tools for specific liver diseases. At the same time, ethical, legal, and talent development challenges, and others must be carefully addressed to bridge the gap and safely and eppectively apply AI in clinical practice.

Objective: To investigate the effect of Kupffer cells on liver regeneration with metabolic associated fatty liver disease (MAFLD) induced by a methionine-choline-deficient (MCD) diet in mice. Methods: Eight-week-old C57BL/6J male mice were randomly divided into three groups: control (normal diet), MAFLD model (MCD feeding), and MAFLD remission (MCD feeding followed by a normal diet after 5 weeks). Liver biochemical indices were detected. Liver tissue pathological morphology was analyzed. Kupffer cells infiltration and hepatocyte proliferation conditions were detected by immunofluorescence staining. Statistical analyses were performed using the t-test, one-way ANOVA, Tukey test, Dunnett test, or Two-way ANOVA test according to different data. Results: The MAFLD model group mice had severe liver lipid accumulation and delayed hepatocyte proliferation. The serum alanine aminotransferase, aspartate aminotransferase, and triglyceride content in the MAFLD model group were increased by 8.10 times, 4.69 times, and 7.32 times, respectively, in comparison to the control group, as indicated by the results of biochemical index detection following five weeks, and this phenomenon was accompanied by a decrease in Kupffer cells. The MAFLD model group had an approximate reduction of 50% in Kupffer cells count compared to the control group. The addition of Kupffer cells had restored the normalized hepatocyte proliferation capacity and alleviated liver steatosis in vitro or through dietary change. Conclusion: The proliferation of hepatocytes has a certain stimulating effect with the supplementation of Kupffer cells in MCD-induced MAFLD mice.

Objective: To construct Slc27a5 gene knockout mice and investigate changed conditions in the serum lipidomics. Methods: Liver tissues and serum samples were collected from wild-type and Slc27a5 gene knockout mice at different time points. Hematoxylin-eosin staining was used to observe hepatic pathological changes. Immunofluorescence staining was used to detect the expression of α-smooth muscle actin and F4/80 proteins. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze changes in serum lipid composition. The comparison of quantitative data was performed using the t-test between groups. Results: The percentage area of α-smooth muscle actin staining (7.33% ± 3.08% vs. 1.14% ± 0.30%, t=3.996, P<0.01) and F4/80 staining area (2.48% ± 0.71% vs. 0.76% ± 0.19%, t=4.683, P<0.01) was significantly higher in Slc27a5 gene-deficient mice than in wild-type mice in liver tissue at 24 months of age. The results of the serum lipidomics analysis indicated significant alterations in lipid composition of Slc27a5 gene-deficient mice. Compared with wild-type mice, the serum of Slc27a5 gene-deficient mice had increased levels of 19 types of phosphatidylinositols and 14 types of phosphatidylcholines and decreased levels of 17 types of phosphatidylethanolamines. Conclusion: Spontaneous liver fibrosis induced by Slc27a5 deficiency in a mouse model is accompanied by significant remodeling of the serum lipid profiles.

The continuous advancement of artificial intelligence (AI)-related technologies is promoting a diagnosis and treatment model for fatty liver disease toward precision medicine. AI assistance reduces human error and enhances the accuracy of non-invasive diagnostics in the field of imaging. Additionally, AI can automatically identify and quantify key histological features when combined with multi-omics data in the field of pathology and can also build more efficient diagnostic and risk assessment models; meanwhile, it aids in personalized treatment decisions and outcome prediction. However, problems such as data heterogeneity, insufficient algorithm interpretability, and lack of multi-center validation remain to be solved, thus necessitating interdisciplinary and multi-center collaboration to promote the in-depth application of AI in the clinical practice of fatty liver disease. This review summarized the current research progress of AI in the diagnosis and treatment of fatty liver disease and discusses the existing issues and challenges.

Objective: To construct a lentiviral plasmid expressing neuropilin-1 (NRP1) and a HepG2-sodium taurocholate cotransporting polypeptide (NTCP) capable of overexpressing stable cell line NRP1 so as to study the susceptibility of this cell line to hepatitis B virus (HBV). Methods: The plasmids pcDNA3.1-NRP1/Myc His B and pCDH-CMV-MCS-EF1-GFP-BSD were used as templates for amplification. The recombinant plasmid pCDH-NRP1-GFP-BSD was obtained using seamless cloning technology. HepG2-NTCP cells were transduced with the recombinant plasmid into lentivirus following packaging. Stable overexpression of NRP1 was obtained following screening of blasticidin S deaminase (BSD) and monoclonal antibody in HepG2-NTCP cell lines. The susceptibility of the resulting cell line to HBV was analyzed by detecting HBV-related markers post-infection. Data between groups were compared using the t-test. Results: The restriction enzyme digestion and sequencing analysis confirmed the successful construction and identification of the recombinant plasmid containing NRP1. Western blot, RT-qPCR, and fluorescence microscopy results showed that the stable overexpression of the targeted NRP1gene had capability in HepG2-NTCP cells. Compared to the control group, NRP1-expressed stable cell lines showed approximately a two-fold increase in efficiency rate in HBV infection. Intracellular HBV covalently closed circular DNA (cccDNA), mRNA, DNA, and viral proteins, including HBsAg, HBeAg, and HBc, were significantly elevated, nearly two-fold, following HBV infection. Conclusion: A stable monoclonal cell line overexpressing NRP1 was successfully constructed, which supports highly efficient HBV infection in vitro and provides a new tool for studying the mechanisms of chronic hepatitis B infection.

Liver failure is severe liver damage caused by multiple factors, with a very high mortality rate. Artificial liver support systems have become a core strategy for alternative or bridging therapy in the context of the rapid progression of liver failure and high mortality rates with comprehensive internal medicine therapy. Non-bioartificial livers mainly serve as partial substitutes for liver function improvement through procedures such as perfusion, dialysis, and filtration methods. Bioartificial livers provide liver support therapy for patients by integrating detoxification, synthesis, and metabolic functions to simulate hepatic biosynthesis, filling the gap that non-bioartificial livers cannot perform and addressing the difficulties of non-bioartificial livers' heavy reliance on blood products. This paper focuses on reviewing the basic and clinical research progress of bioartificial livers, providing a multidimensional perspective to accelerate their clinical translation.

Liver fibrosis is a pathological change caused by hepatocyte inflammation and necrosis due to various etiologies, leading to excessive deposition of the extracellular matrix. Furthermore, it can progress to liver cirrhosis or even cancer if not detected and treated in a timely manner. Therefore, early-stage diagnosis and timely intervention are of great significance for the prevention of liver cirrhosis and cancer. In recent years, the non-invasive diagnosis of liver fibrosis still has certain limitations, hence an ideal non-invasive diagnostic method for early-stage remains a research hotspot. Chitinase-3-like protein 1 (CHI3L1) is a member of the chitinase family, encoded by the human CHI3L1 gene, which is highly expressed in the liver, playing an important role in various inflammatory and fibrotic disease processes with its secretion as a glycoprotein with cytokine and growth factor properties. Recent studies have shown that serum CHI3L1, as an emerging biomarker, has been widely used in the screening and diagnosis of liver-related diseases. This paper reviews the role of serum CHI3L1 in the diagnosis of liver fibrosis non-invasively and its relationship with the staging of liver fibrosis, cirrhosis, and primary liver cancer, providing references for clinical treatment.