Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 85.676
Filtrar
1.
Zhonghua Gan Zang Bing Za Zhi ; 32(6): 489-492, 2024 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-38964889

RESUMO

Thrombocytopenia is one of the common complications of cirrhotic patients, which can induce an increasing bleeding risk and closely correlate with bleeding following invasive procedures. Consequently, how to respond to thrombocytopenia is crucial for improving the prognosis of patients with cirrhosis. This article reviews the main mechanisms of cirrhosis concurrent with thrombocytopenia, as well as the corresponding clinical management strategies.


Assuntos
Cirrose Hepática , Trombocitopenia , Humanos , Trombocitopenia/terapia , Trombocitopenia/etiologia , Cirrose Hepática/complicações , Cirrose Hepática/terapia
2.
Zhonghua Gan Zang Bing Za Zhi ; 32(6): 493-496, 2024 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-38964890

RESUMO

Hypoalbuminemia is one of the important clinical features of decompensated cirrhosis. As the disease progresses, not only does the total albumin concentration decrease, but so does the proportion of albumin that remains structurally and functionally intact. The structural and functional integrity of albumin is essential for its normal physiological role in the body. This led to the concept of "effective albumin concentration," which may be much lower than the total albumin concentration routinely measured clinically in patients with advanced cirrhosis. Liquid chromatography-tandem mass spectrometry, and electron paramagnetic resonance (EMR) are emerging technologies for effective albumin concentration detection, showing promising clinical application prospects, but research in patients with cirrhosis is still in the preliminary stage. Therefore, this article will comprehensively summarize the latest research on the aspects of effective albumin detection methods, liquid chromatography-tandem mass spectrometry, and electron paramagnetic resonance, as well as their applications.


Assuntos
Espectrometria de Massas em Tandem , Humanos , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Albumina Sérica/análise , Cirrose Hepática/diagnóstico , Cirrose Hepática/sangue , Hipoalbuminemia/diagnóstico , Hipoalbuminemia/sangue
3.
Zhonghua Gan Zang Bing Za Zhi ; 32(6): 504-507, 2024 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-38964892

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a common concomitant disease in adults with type 2 diabetes mellitus (T2DM) and prediabetes. Therefore, T2DM/NAFLD patient populations are at high risk for cardiovascular disease. The occurrence and progression of non-alcoholic fatty liver disease-related liver fibrosis and cardiovascular disease have a severe impact on the patient's prognosis and mortality rate. The American Diabetes Association's 2024 "Guidelines for the Standardized Management of Diabetes" put forward recommendations relevant to the screening, evaluation, treatment, and management of NAFLD in T2DM and prediabetic populations, as well as liver fibrosis. The important measures for decelerating liver inflammation and fibrosis progression and the risk of cardiovascular disease are based on improvements in lifestyle methods, weight loss, and blood sugar control.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Estados Unidos , Estado Pré-Diabético/terapia , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/complicações , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/terapia , Cirrose Hepática/complicações , Cirrose Hepática/terapia , Cirrose Hepática/diagnóstico
4.
Zhonghua Gan Zang Bing Za Zhi ; 32(6): 481-483, 2024 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-38964887

RESUMO

Managing cirrhosis complications is an important measure for improving patients' clinical outcomes. Therefore, in order to provide a complete disease assessment and comprehensive treatment, improve quality of life, and improve the prognosis for patients with cirrhosis, it is necessary to pay attention to complications such as thrombocytopenia and portal vein thrombosis in addition to common or severe complications such as ascites, esophagogastric variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome. The relevant concept that an effective albumin concentration is more helpful in predicting the cirrhosis outcome is gradually being accepted; however, the detection method still needs further standardization and commercialization.


Assuntos
Encefalopatia Hepática , Cirrose Hepática , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/terapia , Síndrome Hepatorrenal/etiologia , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/terapia , Ascite/etiologia , Ascite/terapia , Ascite/diagnóstico , Trombocitopenia/etiologia , Trombocitopenia/diagnóstico , Trombocitopenia/terapia , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia
5.
Zhonghua Gan Zang Bing Za Zhi ; 32(6): 508-516, 2024 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-38964893

RESUMO

Objective: To explore the related factors of thrombocytopenia (TCP) occurrence in patients with cirrhosis. Methods: A cross-sectional study was conducted. Inpatients with an initial diagnosis of cirrhosis at Peking University First Hospital from January 1, 2010 to December 31, 2020 were included. Clinical data such as demographic characteristics, etiology of cirrhosis, complications of cirrhosis, laboratory indicators, Child-Pugh grade, invasive procedures, and mortality during hospitalization were collected. A logistic regression model was used to explore the related factors of TCP occurrence in patients with cirrhosis. Categorical variables were compared by the χ(2) test. The inter-group comparison was performed using continuous variables, a t-test, one-way analysis of variance (ANOVA), or a nonparametric test. Results: There were a total of 2 592 cases of cirrhosis. 75 cases with incomplete clinical data were excluded. 2 517 cases were included for analysis. The median age was 58 (50, 67) years. Males accounted for 64%. 1 435 cases (57.0%) developed TCP, and 434 cases (17.2%) had grade 3-4 TCP. Gender, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and concomitant esophagogastric varices (EGV) were the major factors associated with TCP. Females were more prone to combine with TCP (OR=1.32, 95%CI: 1.12-1.56, P=0.001). Patients combined with EGV (OR=3.09, 95%CI: 2.63-3.65, P<0.001) were more prone to develop TCP, which was associated with the increased incidence of hypersplenism (P<0.001). Patients with PBC (OR=0.64, 95%CI: 0.50-0.82, P<0.001) and PSC (OR=0.23, 95%CI: 0.06-0.65, P=0.010) were less prone to develop TCP, which was due to the shorter prothrombin time and better coagulation function of PBC patients (P<0.001), and the lower proportion of hypersplenism in combined PSC patients (P=0.004). Patients with TCP and grade 3-4 TCP had a higher rate of hemostatic procedures (P<0.05), but a lower rate of liver biopsy (P<0.05). Patients with grade 3-4 TCP had a higher nosocomial mortality rate compared to those without (P=0.004). Conclusion: TCP is common in patients with cirrhosis. However, TCP occurrence is higher in female patients with EGV and lower in patients combined with PBC and PSC. TCP affects invasive procedures and is associated with adverse outcomes.


Assuntos
Cirrose Hepática , Trombocitopenia , Humanos , Estudos Transversais , Trombocitopenia/etiologia , Masculino , Pessoa de Meia-Idade , Feminino , Cirrose Hepática/complicações , Idoso , Fatores de Risco , Modelos Logísticos , Cirrose Hepática Biliar/complicações , Adulto
6.
Zhonghua Gan Zang Bing Za Zhi ; 32(6): 517-524, 2024 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-38964894

RESUMO

Objective: To measure the overall and lobulated volume of the liver with different degrees of liver fibrosis and to further observe pathological changes such as liver microvasculature, hepatocyte apoptosis, and regeneration in order to understand the macroscopic volume changes of the liver during liver fibrosis and its relationship with liver tissue microscopic pathology in patients with chronic liver disease. Methods: 53 patients with chronic hepatitis B, alcoholic fatty liver disease, autoimmune liver disease, nonalcoholic fatty liver disease, and drug-induced chronic liver disease who underwent both liver biopsy tissue and abdominal magnetic resonance imaging were collected. Patients were divided into early (F1-2), middle (F3-4), and late (F5-6) in accordance with the Ishak fibrosis stage and Masson stain. The liver and spleen volumes were measured using ITK-SNAP software. CD31 immunohistochemical staining was used to reflect intrahepatic angiogenesis. Ki67 and HNF-4α multiplex immunohistochemical staining were used to reflect hepatocyte regeneration. GS staining was used to determine parenchymal extinction lesions. TUNEL staining was used to observe hepatocyte apoptosis. Spearman correlation analysis was used to analyze the relationship between liver volume changes and liver histopathological changes. Results: As liver fibrosis progressed, the total liver volume and right lobe liver volume gradually decreased (P<0.05), while the spleen volume gradually increased (P<0.05). The expression of CD31 and GS gradually increased (P<0.05), and the expression of Ki67 first increased and then decreased (P<0.05). The positivity rate of CD31 was negatively correlated with the right lobe liver volume (r=-0.609, P<0.001) and the total liver volume (r=-0.363, P=0.017). The positivity rate of Ki67 was positively correlated with the right lobe liver volume (r=0.423, P=0.018), while the positivity rate of apoptotic cells was significantly negatively correlated with the total liver volume (r=-0.860, P<0.001). The positivity rate of GS was negatively correlated with the right lobe liver volume (r=-0.440, P=0.002), and the number of PELs was negatively correlated with RV (r=-0.476, P=0.013). The CD31 positive staining area was negatively correlated with the Ki67 positive staining area(r=-0.511, P=0.009). Conclusion: As liver fibrosis progresses, patients with chronic liver disease have a depletion in total liver volume and right lobe liver volume, and this is mainly in correlation with fewer liver cells and liver tissue microvasculature disorders.


Assuntos
Cirrose Hepática , Fígado , Humanos , Cirrose Hepática/patologia , Fígado/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Regeneração Hepática , Doença Crônica , Hepatócitos/patologia , Hepatócitos/metabolismo , Tamanho do Órgão , Apoptose , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia
7.
Clin Exp Pharmacol Physiol ; 51(8): e13907, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38965675

RESUMO

OBJECTIVE: Most cases of hepatocellular carcinoma (HCC) arise as a consequence of cirrhosis. In this study, our objective is to construct a comprehensive diagnostic model that investigates the diagnostic markers distinguishing between cirrhosis and HCC. METHODS: Based on multiple GEO datasets containing cirrhosis and HCC samples, we used lasso regression, random forest (RF)-recursive feature elimination (RFE) and receiver operator characteristic analysis to screen for characteristic genes. Subsequently, we integrated these genes into a multivariable logistic regression model and validated the linear prediction scores in both training and validation cohorts. The ssGSEA algorithm was used to estimate the fraction of infiltrating immune cells in the samples. Finally, molecular typing for patients with cirrhosis was performed using the CCP algorithm. RESULTS: The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model. In both the training and validation cohorts, the model exhibited an area under the curve (AUC) greater than 0.9 and a kappa value of approximately 0.9. Additionally, the calibration curve demonstrated excellent concordance between observed and predicted incidence rates. Comparatively, HCC displayed overall downregulation of infiltrating immune cells compared to cirrhosis. Notably, CCBE1 showed strong correlations with the tumour immune microenvironment as well as genes associated with cell death and cellular ageing processes. Furthermore, cirrhosis subtypes with high linear predictive scores were enriched in multiple cancer-related pathways. CONCLUSION: In conclusion, we successfully identified diagnostic markers distinguishing between cirrhosis and hepatocellular carcinoma and developed a novel diagnostic model for discriminating the two conditions. CCBE1 might exert a pivotal role in regulating the tumour microenvironment, cell death and senescence.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular , Cirrose Hepática , Neoplasias Hepáticas , Aprendizado de Máquina , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Cirrose Hepática/diagnóstico , Cirrose Hepática/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Diagnóstico Diferencial , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos
8.
Sci Rep ; 14(1): 15349, 2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961190

RESUMO

Precision-cut liver slices (PCLS) are increasingly used as a model to investigate anti-fibrotic therapies. However, many studies use PCLS from healthy animals treated with pro-fibrotic stimuli in culture, which reflects only the early stages of fibrosis. The effects of different culture conditions on PCLS from cirrhotic animals has not been well characterized and there is no consensus on optimal methods. In this study, we report a method for the collection and culture of cirrhotic PCLS and compare the effect of common culture conditions on viability, function, and gene expression. Additionally, we compared three methods of RNA isolation and identified a protocol with high yield and purity. We observed significantly increased albumin production when cultured with insulin-transferrin-selenium and dexamethasone, and when incubated on a rocking platform. Culturing with insulin-transferrin-selenium and dexamethasone maintained gene expression closer to the levels in fresh slices. However, despite stable viability and function up to 4 days, we found significant changes in expression of key genes by day 2. Interestingly, we also observed that cirrhotic PCLS maintain viability in culture longer than slices from healthy animals. Due to the influence of matrix stiffness on fibrosis and hepatocellular function, it is important to evaluate prospective anti-fibrotic therapies in a platform that preserves tissue biomechanics. PCLS from cirrhotic animals represent a promising tool for the development of treatments for chronic liver disease.


Assuntos
Dexametasona , Cirrose Hepática , Fígado , Animais , Ratos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Cirrose Hepática/genética , Dexametasona/farmacologia , Masculino , RNA/isolamento & purificação , RNA/genética , RNA/metabolismo , Insulina/metabolismo , Insulina/farmacologia , Ratos Sprague-Dawley , Selênio/farmacologia , Técnicas de Cultura de Tecidos/métodos
9.
Sci Rep ; 14(1): 15343, 2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961222

RESUMO

This study aimed to construct a non-invasive diagnostic nomogram based on high-frequency ultrasound and magnetic resonance imaging results for early liver cirrhosis patients with chronic hepatitis B (CHB) which cannot be detected by conventional non-invasive examination methods but can only be diagnosed through invasive liver puncture for pathological examination. 72 patients with CHB were enrolled in this prospective study, and divided into S4 stage of liver cirrhosis and S0-S3 stage of non-liver cirrhosis according to pathological findings. Binary logistic regression analysis was performed to identify independent predictors, and a diagnostic nomogram was constructed for CHB-related early cirrhosis. It was validated and calibrated by bootstrap self-extraction. Binary logistic regression analysis showed that age (OR 1.14, 95% CI (1.04-1.27)), right hepatic vein diameter (OR 0.43, 95% CI 0.23-0.82), presence or absence of nodules (OR 31.98, 95% CI 3.84-266.08), and hepatic parenchymal echogenicity grading (OR 12.82, 95% CI 2.12-77.51) were identified as independent predictive indicators. The nomogram based on the 4 factors above showed good performance, with a sensitivity and specificity of 90.70% and 89.66%, respectively. The area under the curve (AUC) of the prediction model was 0.96, and the predictive model showed better predictive performance than APRI score (AUC 0.57), FIB-4 score (AUC 0.64), INPR score (AUC 0.63), and LSM score (AUC 0.67). The calibration curve of the prediction model fit well with the ideal curve, and the decision curve analysis showed that the net benefit of the model was significant. The nomogram in this study can detect liver cirrhosis in most CHB patients without liver biopsy, providing a direct, fast, and accurate practical diagnostic tool for clinical doctors.


Assuntos
Hepatite B Crônica , Cirrose Hepática , Nomogramas , Ultrassonografia , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Cirrose Hepática/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Adulto , Imageamento por Ressonância Magnética/métodos , Fígado/patologia , Fígado/diagnóstico por imagem
10.
Physiol Rep ; 12(13): e16133, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38961593

RESUMO

Decompensated liver disease is complicated by multi-organ failure and poor prognosis. The prognosis of patients with liver failure often dictates clinical management. Current prognostic models have focused on biomarkers considered as individual isolated units. Network physiology assesses the interactions among multiple physiological systems in health and disease irrespective of anatomical connectivity and defines the influence or dependence of one organ system on another. Indeed, recent applications of network mapping methods to patient data have shown improved prediction of response to therapy or prognosis in cirrhosis. Initially, different physical markers have been used to assess physiological coupling in cirrhosis including heart rate variability, heart rate turbulence, and skin temperature variability measures. Further, the parenclitic network analysis was recently applied showing that organ systems connectivity is impaired in patients with decompensated cirrhosis and can predict mortality in cirrhosis independent of current prognostic models while also providing valuable insights into the associated pathological pathways. Moreover, network mapping also predicts response to intravenous albumin in patients hospitalized with decompensated cirrhosis. Thus, this review highlights the importance of evaluating decompensated cirrhosis through the network physiologic prism. It emphasizes the limitations of current prognostic models and the values of network physiologic techniques in cirrhosis.


Assuntos
Cirrose Hepática , Humanos , Cirrose Hepática/fisiopatologia , Cirrose Hepática/diagnóstico , Prognóstico
11.
Zhonghua Gan Zang Bing Za Zhi ; 32(6): 484-488, 2024 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-38964888

RESUMO

Portal vein thrombosis (PVT) is divided into cirrhotic and non-cirrhotic PVTs. The incidence rate of PVT varies greatly among different clinical stages of cirrhosis, with an overall incidence rate of about 13.92%, and the prevalence of cirrhotic PVT following splenectomy is as high as 60%. The pathogenesis of cirrhotic PVT is still unclear. However, the activation of Janus kinase/signal transduction and activator transcription signaling pathways, the rise in the expression of von Willebrand factor, and the gut microbiota along with its metabolite trimethylamine-N-oxide play an important role in the injury of vascular endothelial cells and the formation of PVT in cirrhosis. Therefore, these could be a new target for cirrhotic PVT prevention and treatment.


Assuntos
Cirrose Hepática , Veia Porta , Trombose Venosa , Humanos , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controle , Cirrose Hepática/complicações , Transdução de Sinais , Metilaminas/metabolismo , Microbioma Gastrointestinal , Fator de von Willebrand/metabolismo , Janus Quinases/metabolismo
12.
Anal Chim Acta ; 1316: 342802, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-38969400

RESUMO

BACKGROUND: Cirrhosis represents the terminal stage of liver disease progression and timely intervention in a diseased liver can enhance the likelihood of recovery. Viscosity, a crucial parameter of the cellular microenvironment, is intricately linked to the advancement of cirrhosis. However, viscosity monitoring still faces significant challenges in achieving non-invasive and rapid early diagnosis of cirrhosis. Near-infrared (NIR) fluorescence imaging has the advantages of high sensitivity, non-destructive detection, and ignoring background fluorescence interference, plays an important role in diagnosing and treating various biological diseases. Hence, monitoring cellular viscosity changes with NIR fluorescence probe holds great significance in the early diagnosis of cirrhosis. RESULTS: In this study, the NIR fluorescence probe based on the intramolecular charge transfer (TICT) mechanism was developed for imaging applications in mouse model of liver cirrhosis. A molecular rotor-type viscosity-responsive probe was synthesized by linking dioxanthracene groups via carbon-carbon double bonds. The probe demonstrated remarkable sensitivity, high selectivity and photostability, with its responsiveness to viscosity largely unaffected by factors such as polarity, pH, and interfering ions. The probe could effectively detect various drug-induced changes in cellular viscosity, enabling the differentiation between normal cells and cancerous cells. Furthermore, the enhanced tissue penetration capabilities of probe facilitated its successful application in mouse model of liver cirrhosis, allowing for the assessment of liver disease severity based on fluorescence intensity and providing a powerful tool for early diagnosis of cirrhosis. SIGNIFICANCE: A NIR viscosity-sensitive fluorescent probe was specifically designed to effectively monitor alterations in cellular and organ viscosity, which could advance the understanding of the biological characteristics of cancer and provide theoretical support for the early diagnosis of cirrhosis. Overall, this probe held immense potential in monitoring viscosity-related conditions, expanding the range of biomedical tools available.


Assuntos
Corantes Fluorescentes , Cirrose Hepática , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Animais , Humanos , Camundongos , Imagem Óptica , Viscosidade , Raios Infravermelhos , Estrutura Molecular
13.
BMJ Case Rep ; 17(7)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38960420

RESUMO

A woman in her mid-20s, a known case of congenital afibrinogenaemia, presented with abdominal pain and distension. She was diagnosed with decompensated liver cirrhosis due to Budd-Chiari syndrome. She underwent deceased donor liver transplantation. Preoperatively, her serum fibrinogen level was undetectable and prothrombin time and international normalised ratio (INR) were unrecordable. Intraoperatively, she was given thromboelastography-guided human fibrinogen concentrate. Postoperatively, her fibrinogen, prothrombin time and INR normalised rapidly. This report summarises the rare occurrence of a complication of hypercoagulability (Budd-Chiari syndrome) in the setting of congenital hypocoagulability (congenital afibrinogenaemia). In this report, we discuss the simultaneous management of these two clinical problems and the curative role of liver transplantation.


Assuntos
Afibrinogenemia , Síndrome de Budd-Chiari , Transplante de Fígado , Humanos , Síndrome de Budd-Chiari/etiologia , Afibrinogenemia/complicações , Feminino , Adulto , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Fibrinogênio/uso terapêutico , Coeficiente Internacional Normatizado
14.
Nat Commun ; 15(1): 5506, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951527

RESUMO

Obesity is a major cause of metabolic dysfunction-associated steatohepatitis (MASH) and is characterized by inflammation and insulin resistance. Interferon-γ (IFNγ) is a pro-inflammatory cytokine elevated in obesity and modulating macrophage functions. Here, we show that male mice with loss of IFNγ signaling in myeloid cells (Lyz-IFNγR2-/-) are protected from diet-induced insulin resistance despite fatty liver. Obesity-mediated liver inflammation is also attenuated with reduced interleukin (IL)-12, a cytokine primarily released by macrophages, and IL-12 treatment in vivo causes insulin resistance by impairing hepatic insulin signaling. Following MASH diets, Lyz-IFNγR2-/- mice are rescued from developing liver fibrosis, which is associated with reduced fibroblast growth factor (FGF) 21 levels. These results indicate critical roles for IFNγ signaling in macrophages and their release of IL-12 in modulating obesity-mediated insulin resistance and fatty liver progression to MASH. In this work, we identify the IFNγ-IL12 axis in regulating intercellular crosstalk in the liver and as potential therapeutic targets to treat MASH.


Assuntos
Fígado Gorduroso , Resistência à Insulina , Interferon gama , Interleucina-12 , Fígado , Macrófagos , Camundongos Knockout , Obesidade , Transdução de Sinais , Animais , Interferon gama/metabolismo , Interleucina-12/metabolismo , Masculino , Obesidade/metabolismo , Camundongos , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Macrófagos/metabolismo , Fígado/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos , Receptores de Interferon/metabolismo , Receptores de Interferon/genética , Receptor de Interferon gama , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Cirrose Hepática/genética
15.
Sci Rep ; 14(1): 15099, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956264

RESUMO

Liver fibrosis is a hallmark of chronic liver disease which could lead to liver cirrhosis or liver cancer. However, there is currently lack of a direct treatment for liver fibrosis. Boiling histotripsy (BH) is an emerging non-invasive high-intensity focused ultrasound technique that can be employed to mechanically destruct solid tumour at the focus via acoustic cavitation without significant adverse effect on surrounding tissue. Here, we investigated whether BH can mechanically fractionate liver fibrotic tissue thereby exhibiting an anti-fibrotic effect in an animal model of liver fibrosis. BH-treated penumbra and its identical lobe showed reduced liver fibrosis, accompanied by increased hepatocyte specific marker expression, compared to the BH-untreated lobe. Furthermore, BH treatment improved serological liver function markers without notable adverse effects. The ability of BH to reduce fibrosis and promote liver regeneration in liver fibrotic tissue suggests that BH could potentially be an effective and reliable therapeutic approach against liver fibrosis.


Assuntos
Modelos Animais de Doenças , Ablação por Ultrassom Focalizado de Alta Intensidade , Cirrose Hepática , Animais , Cirrose Hepática/terapia , Cirrose Hepática/patologia , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Masculino , Regeneração Hepática , Fígado/patologia , Fígado/metabolismo , Camundongos , Ratos
16.
BMC Med ; 22(1): 278, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956533

RESUMO

BACKGROUND: APRI and FIB-4 scores are used to exclude clinically significant fibrosis (defined as stage ≥ F2) in patients with chronic viral hepatitis. However, the cut-offs for these scores (generated by Youden indices) vary between different patient cohorts. This study aimed to evaluate whether serum dithiothreitol-oxidizing capacity (DOC), i.e., a surrogate test of quiescin sulfhydryl oxidase-1, which is a matrix remodeling enzyme, could be used to non-invasively identify significant fibrosis in patients with various chronic liver diseases (CLDs). METHODS: Diagnostic performance of DOC was compared with APRI and FIB-4 for identifying significant fibrosis. ROC curve analyses were undertaken in: a) two chronic hepatitis B (CHB) cohorts, independently established from hospitals in Wenzhou (n = 208) and Hefei (n = 120); b) a MASLD cohort from Wenzhou hospital (n = 122); and c) a cohort with multiple CLD etiologies (except CHB and MASLD; n = 102), which was identified from patients in both hospitals. Cut-offs were calculated using the Youden index. All CLD patients (n = 552) were then stratified by age for ROC curve analyses and cut-off calculations. RESULTS: Stratified by CLD etiology or age, ROC curve analyses consistently showed that the DOC test was superior to APRI and FIB-4 for discriminating between clinically significant fibrosis and no fibrosis, when APRI and FIB-4 showed poor/modest diagnostic performance (P < 0.05, P < 0.01 and P < 0.001 in 3, 1 and 3 cohort comparisons, respectively). Conversely, the DOC test was equivalent to APRI and FIB-4 when all tests showed moderate/adequate diagnostic performances (P > 0.05 in 11 cohort comparisons). DOC had a significant advantage over APRI or FIB-4 scores for establishing a uniform cut-off independently of age and CLD etiology (coefficients of variation of DOC, APRI and FIB-4 cut-offs were 1.7%, 22.9% and 47.6% in cohorts stratified by CLD etiology, 2.0%, 26.7% and 29.5% in cohorts stratified by age, respectively). The uniform cut-off was 2.13, yielded from all patients examined. Surprisingly, the uniform cut-off was the same as the DOC upper limit of normal with a specificity of 99%, estimated from 275 healthy control individuals. Hence, the uniform cut-off should possess a high negative predictive value for excluding significant fibrosis in primary care settings. A high DOC cut-off with 97.5% specificity could be used for detecting significant fibrosis (≥ F2) with an acceptable positive predictive value (87.1%). CONCLUSIONS: This proof-of-concept study suggests that the DOC test may efficiently rule out and rule in significant liver fibrosis, thereby reducing the numbers of unnecessary liver biopsies. Moreover, the DOC test may be helpful for clinicians to exclude significant liver fibrosis in the general population.


Assuntos
Biomarcadores , Ditiotreitol , Cirrose Hepática , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Feminino , Adulto , Idoso , Oxirredução , Curva ROC , Estudos de Coortes , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/sangue , Estudo de Prova de Conceito
17.
Front Public Health ; 12: 1383065, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38989121

RESUMO

Objectives: The study aimed to estimate the role of liver fibrosis in the association between occupational physical activity (OPA) and blood pressure (BP), which is modified by lifestyle factors. Methods: The questionnaire survey and physical examination were completed among 992 construction workers in Wuhan, China. Associations between OPA or lifestyle factors and liver fibrosis indices and blood pressure were assessed using generalized additive models. The mediation analysis was used to evaluate the role of liver fibrosis in the association between OPA and lifestyle factors and BP. Results: Moderate/high OPA group workers had an increased risk of liver fibrosis [odds ratio (OR) = 1.69, 95% confidence intervals (CI): 1.16-2.47, P < 0.05] compared with low OPA group workers. Smoking or drinking alcohol was related to liver fibrosis (aspartate aminotransferase to platelet ratio index: OR = 2.22, 95% CI: 1.07-4.62 or OR = 2.04, 95% CI: 1.00-4.15; P < 0.05). Compared with non-drinkers, drinkers were related to a 2.35-mmHg increase in systolic blood pressure (95% CI: 0.09-4.61), and a 1.60-mmHg increase in diastolic blood pressure (95% CI: 0.08-3.13; P < 0.05). We found a significant pathway, "OPA → liver fibrosis → blood pressure elevation," and lifestyle factors played a regulatory role in the pathway. Conclusion: OPA or lifestyle factors were associated with liver fibrosis indices or BP in construction workers. Furthermore, the association between OPA and BP may be partially mediated by liver fibrosis; lifestyle factors strengthen the relationship between OPA and BP and the mediation role of liver fibrosis in the relationship.


Assuntos
Pressão Sanguínea , Exercício Físico , Estilo de Vida , Cirrose Hepática , Humanos , Masculino , Adulto , China/epidemiologia , Pressão Sanguínea/fisiologia , Pessoa de Meia-Idade , Inquéritos e Questionários , Feminino , Consumo de Bebidas Alcoólicas , Fatores de Risco , Fumar , Hipertensão/epidemiologia , Estudos Transversais
18.
Nihon Shokakibyo Gakkai Zasshi ; 121(7): 580-588, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38987168

RESUMO

Improvement and worsening of portal hypertension after direct acting antiviral agent (DAA) treatment for hepatitis C virus-related cirrhosis have been reported, and a consensus remains elusive. In this study, we underscored on the intraperitoneal shunt formed via portal hypertension and examined how the shunt system confirmed by computed tomography (CT) changes before and after treatment in cases in which sustained virological response (SVR) was attained with DAAs. Of the cases in which we achieved an SVR of 24 with DAA treatment for hepatitis C virus-related cirrhosis at our hospital, 83 cases in which CT images were taken before and after treatment were investigated. If the intraperitoneal shunt diameter changed by 20% or more, it was analyzed as an increase or decrease. In 29 patients, intraperitoneal shunt enlargement was noted. When examining factors related to the increase, multivariate analysis detected the FIB4 index at the end of the DAA treatment. Conversely, only four cases were observed in which the size decreased. At the end of treatment, the FIB4 index was the most important factor in increasing the intraperitoneal shunt after DAA treatment for hepatitis C virus-related cirrhosis, and fibrosis was believed to be an influencing factor.


Assuntos
Antivirais , Hepatite C , Humanos , Antivirais/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Hepatite C/tratamento farmacológico , Hepatite C/complicações , Tomografia Computadorizada por Raios X , Hipertensão Portal , Cirrose Hepática/cirurgia
19.
Mol Med Rep ; 30(3)2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-38963032

RESUMO

Cirrhosis impairs macrophage function and disrupts bile acid homeostasis. Although bile acids affect macrophage function in patients with sepsis, whether and how the bile acid profile is changed by infection in patients with cirrhosis to modulate macrophage function remains unclear. The present study aimed to investigate the changes in the bile acid profile of patients with cirrhosis and infection and their effects on macrophage function. Serum was collected from 20 healthy subjects, 18 patients with cirrhosis and 39 patients with cirrhosis and infection. Bile acid profiles were detected using high­performance liquid chromatography­triple time­of­flight mass spectrometer. The association between bile acid changes and infection was analysed using receiver operating characteristic (ROC) curves. Infection­altered bile acids were used in combination with lipopolysaccharides (LPS) to stimulate RAW264.7/THP­1 cells in vitro. The migratory capacity was evaluated using wound healing and Transwell migration assays. The expression of Arg­1, iNOS, IκBα, phosphorylated (p­)IκBα and p65 was examined with western blotting and immunofluorescence, Tnfα, Il1b and Il6 mRNA was examined with RT­qPCR, and CD86, CD163 and phagocytosis was measured with flow cytometry. The ROC curves showed that decreased hyodeoxycholic acid (HDCA) and deoxycholic acid (DCA) levels were associated with infection. HDCA or DCA combined with LPS enhanced the phagocytic and migratory ability of macrophages, accompanied by upregulation of iNOS and CD86 protein expression as well as Tnfα, Il1b, and Il6 mRNA expression. However, neither HDCA nor DCA alone showed an effect on these phenotypes. In addition, DCA and HDCA acted synergistically with LPS to increase the expression of p­IκBα and the intranuclear migration of p65. Infection changed the bile acid profile in patients with cirrhosis, among which the reduction of DCA and HDCA associated most strongly with infection. HDCA and DCA enhanced the sensitivity of macrophage function loss to LPS stimulation. These findings suggested a potential role for monitoring the bile acid profile that could help manage patients with cirrhosis and infection.


Assuntos
Ácidos e Sais Biliares , Cirrose Hepática , Ativação de Macrófagos , Macrófagos , Humanos , Cirrose Hepática/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Ácidos e Sais Biliares/metabolismo , Ácidos e Sais Biliares/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Camundongos , Células RAW 264.7 , Animais , Macrófagos/metabolismo , Macrófagos/imunologia , Lipopolissacarídeos , Células THP-1 , Adulto , Idoso , Fagocitose/efeitos dos fármacos , Citocinas/metabolismo , Movimento Celular/efeitos dos fármacos
20.
Sci Rep ; 14(1): 15827, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982109

RESUMO

The influence of liver fibrosis on the rate of liver regeneration and complications following ALPPS has yet to be fully understood. This study aimed to scrutinize the effects of liver fibrosis on the postoperative complications, and prognosis subsequent to ALPPS. Clinical data were collected from patients with primary liver cancer who underwent ALPPS at Peking Union Medical College Hospital between May 2014 and October 2022. The degree of liver fibrosis was assessed using haematoxylin-eosin staining and Sirius red staining. This study encompassed thirty patients who underwent ALPPS for primary liver cancer, and there were 23 patients with hepatocellular carcinoma, 5 with cholangiocarcinoma, and 2 with combined hepatocellular-cholangiocarcinoma. The impact of severe liver fibrosis on the rate of liver regeneration was not statistically significant (P = 0.892). All patients with severe complications belonged to the severe liver fibrosis group. Severe liver fibrosis exhibited a significant association with 90 days mortality (P = 0.014) and overall survival (P = 0.012). Severe liver fibrosis emerges as a crucial risk factor for liver failure and perioperative mortality following the second step of ALPPS. Preoperative liver function impairment is an important predictive factor for postoperative liver failure.


Assuntos
Hepatectomia , Cirrose Hepática , Falência Hepática , Neoplasias Hepáticas , Humanos , Masculino , Feminino , Cirrose Hepática/cirurgia , Cirrose Hepática/patologia , Cirrose Hepática/complicações , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Pessoa de Meia-Idade , Falência Hepática/etiologia , Falência Hepática/patologia , Hepatectomia/efeitos adversos , Idoso , Prognóstico , Complicações Pós-Operatórias/etiologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Veia Porta/patologia , Veia Porta/cirurgia , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Colangiocarcinoma/mortalidade , Adulto , Regeneração Hepática , Fatores de Risco , Estudos Retrospectivos , Resultado do Tratamento , Ligadura
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...