RESUMEN
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.
Asunto(s)
Cirrosis Hepática , Vena Porta , Trombosis de la Vena , Humanos , Trombosis de la Vena/etiología , Trombosis de la Vena/prevención & control , Cirrosis Hepática/complicaciones , Transducción de Señal , Metilaminas/metabolismo , Microbioma Gastrointestinal , Factor de von Willebrand/metabolismo , Quinasas Janus/metabolismoRESUMEN
Objective: intrahepatic portocaval shunt (TIPS) in the treatment of hepatic sinusoidal obstruction syndrome (HSOS). Methods: A retrospective analysis was performed on 27 patients with HSOS who were treated with TIPS in our center from July 2018 to July 2020. The changes of portal vein pressure (PVP), portal vein pressure gradient (PPG) and liver function were observed, so as to evaluate the efficacy. Paired t test was adopted to evaluate the quantitative parameters, while χ (2) test was used to analyze qualitative parameters, with P < 0.05 as statistical difference. Results: PVP decreased from (4.41 ± 0.18) kPa before shunt to (2.69 ± 0.11) kPa after shunt (t = 82.41, P < 0.001), PPG decreased from (3.23 ± 0.18) kPa before shunt to (1.46 ± 0.23) kPa after shunt (t = 32.41, P < 0.001). The liver function improved significantly after operation. After 24 months of follow-up, 3 patients developed stent restenosis and recanalized after balloon dilation. Three patients developed hepatic encephalopathy, which was improved after drug treatment. One patient underwent liver transplantation due to liver failure. Conclusion: TIPS is effective in the treatment of HSOS in the short and medium term, and can provide time for liver transplantation patients to wait for liver source.
Asunto(s)
Encefalopatía Hepática , Enfermedad Veno-Oclusiva Hepática , Hepatopatías , Humanos , Estudios RetrospectivosRESUMEN
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Microvascular invasion (MVI) is considered the major risk factor for postoperative recurrence and metastasis in HCC. The diagnosis of MVI relies on the postoperative pathological assessment of the tumor tissues. Seeking non-invasive methods and biomarkers for evaluation of MVI before surgery has important clinical implications for guiding surgical treatment and improving patients' survival. Recent studies have reported the applications of radiomics technique in prediction of MVI in HCC and showed promising results. Herein we summarized the research progress in CT- or MRI-based radiomics models for prediction of MVI in HCC to provide helpful thinking for further research in this field.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética , Microvasos/patología , Invasividad Neoplásica/patología , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
Objective: The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China. Methods: This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems. Results: According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%). Conclusion: Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.
Asunto(s)
Hipertensión Portal , China/epidemiología , Venas Hepáticas , Humanos , Hipertensión Portal/diagnóstico , Cirrosis Hepática , Presión PortalRESUMEN
Biliary liver disease refers to intrahepatic and extrahepatic bile duct system lesions or bile duct epithelial cells damage, resulting in abnormal liver function, inflammation and fibrosis, which mainly manifests as chronic cholestatic liver disease. The common causes include primary biliary cholangitis, primary sclerosing cholangitis, progressive familial intrahepatic cholangitis, bile duct complications after liver transplantation, and vanishing bile duct syndrome caused by drugs or serious infections, and the most prominent symptoms affecting the patients quality life is pruritus and jaundice. Endoscopic retrograde duodenoscopic cholangiopancreatography and cholangiopancreatoscopy (SpyGlass) and other endoscopic examinations can significantly improve the accuracy of early differential diagnosis,cytology and biopsy of primary sclerosing cholangitis, immunoglobulin G4-related cholangitis and cholangiocarcinoma. Endoscopic nasobiliary drainage, balloon dilatation and intrabiliary stent implantation can significantly improve pruritus symptoms, liver biochemical indicators and prognosis. Therefore, gastrointestinal endoscopy has important value and application prospects in the diagnosis and treatment of biliary liver diseases.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangitis Esclerosante , Colangitis , Colestasis , Hepatopatías , Conductos Biliares Intrahepáticos/patología , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colangitis/complicaciones , Colangitis Esclerosante/diagnóstico , Colestasis/complicaciones , Colestasis/diagnóstico , Colestasis/terapia , Endoscopía Gastrointestinal/efectos adversos , Humanos , Hepatopatías/complicaciones , Prurito/complicacionesRESUMEN
Objective: To investigate the practicability and safety of transjugular liver biopsy (TJLB). Methods: Data of 53 cases with transjugular liver biopsy from June 2015 to June 2020 were collected. LABS-100 was used in all patients who underwent transjugular liver biopsy. Among them, 45 cases and eight were biopsied via hepatic vein and intrahepatic segment of the inferior vena cava. The surgical indications, related complications, and postoperative pathological diagnosis were analyzed and summarized. Results: TJLB was successful in all patients, with an average of 2.8 punctures per case. Satisfactory liver tissue and histopathological diagnosis was obtained in all patients. Two cases developed a cervical hematoma that was improved spontaneously, and one patient developed an intrahepatic hematoma that was improved after conservative treatment. Conclusion: TJLB is a practical and safe method for patients with contraindications to percutaneous liver biopsy.
Asunto(s)
Venas Yugulares , Hepatopatías , Biopsia/efectos adversos , Biopsia/métodos , Biopsia con Aguja/métodos , Humanos , Hepatopatías/patologíaRESUMEN
Objective: To verify Baveno VI criteria, Expanded-Baveno VI criteria, liver stiffness×spleen diameter-to-platelet ratio risk score (LSPS), and platelet count/spleen diameter ratio (PSR) in evaluating the severity value of esophageal varices (EV) in patients with non-cirrhotic portal hypertension (NCPH). Methods: 111 cases of NCPH and 204 cases of hepatitis B cirrhosis who met the diagnostic criteria were included in the study. NCPH included 70 cases of idiopathic non-cirrhotic portal hypertension (INCPH) and 41 cases of nontumoral portal vein thrombosis (PVT). According to the severity of EV on endoscopy, they were divided into the low-bleeding-risk group (no/mild EV) and the high-bleeding-risk group (moderate/severe EV). The diagnostic value of Baveno VI and Expanded-Baveno VI criteria was verified to evaluate the value of LSPS and PSR for EV bleeding risk severity in NCPH patients. The t-test or Mann-Whitney U test was used to compare the measurement data between groups. Comparisons between counting data groups were performed using either the χ2 test or the Fisher exact probability method. Results: Considering endoscopy was the gold standard for diagnosis, the missed diagnosis rates of low/high bleeding risk EVs in INCPH/PVT patients with Baveno VI and Expanded-Baveno VI criteria were 50.0%/30.0% and 53.8%/50.0%, respectively. There were no statistically significant differences in platelet count (PLT), spleen diameter, liver stiffness (LSM), LSPS, and PSR between low-bleeding-risk and high-bleeding-risk groups in INCPH patients, and the area under the receiver operating characteristic curve (AUC) of LSPS and PSR was 0.564 and 0.592, respectively (P=0.372 and 0.202, respectively). There were statistically significant differences in PLT, spleen diameter, LSPS, and PSR between the low and high-bleeding risk groups in PVT patients, and the AUCs of LSPS and PSR were 0.796 and 0.833 (P=0.003 and 0.001, respectively). In patients with hepatitis B cirrhosis, the Baveno VI and Expanded-Baveno VI criteria were used to verify the low bleeding risk EV, and the missed diagnosis rates were 0 and 5.4%, respectively. There were statistically significant differences in PLT, spleen diameter, LSM, LSPS and PSR between the low-bleeding-risk and high-bleeding-risk groups (P<0.001). LSPS and PSR AUC were 0.867 and 0.789, respectively (P<0.05). Conclusion: Baveno VI and Expanded-Baveno VI criteria have a high missed diagnosis rate for EVs with low bleeding risk in patients with INPCH and PVT, while LSPS and PSR have certain value in evaluating EV bleeding risk in PVT patients, which requires further clinical research.
Asunto(s)
Diagnóstico por Imagen de Elasticidad , Várices Esofágicas y Gástricas , Hepatitis B , Hipertensión Portal , Humanos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/diagnóstico , Hemorragia Gastrointestinal , Hipertensión Portal/complicaciones , Hipertensión Portal/diagnóstico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Diagnóstico por Imagen de Elasticidad/métodosRESUMEN
Portal hypertension-related esophagogastric variceal bleeding (EVB) is deadly. Therefore, multidisciplinary management involving hepatologists, digestive endoscopy, radiological intervention, and/or surgery is necessary. Digestive endoscopy is the core of the multidisciplinary approach to the overall management of portal hypertension. It plays an important role in the early warning, emergency treatment, and the prevention of the initial and re-bleeding of portal hypertension accompanied by esophagogastric varices. In addition, gastroscopy with endoscopic ultrasound scanning can enhance the management capabilities of ectopic varices.
Asunto(s)
Várices Esofágicas y Gástricas , Hipertensión Portal , Várices , Endoscopía , Endoscopía Gastrointestinal , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/terapia , Hemorragia Gastrointestinal/diagnóstico por imagen , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Humanos , Hipertensión Portal/complicacionesRESUMEN
OBJECTIVE: In recent years, studies have shown that noncoding RNA (circRNA) is an important regulatory molecule involved in cell physiology and pathology. Herein, we analyzed the role of circRNA-68566 in the regulation of myocardial ischemia-reperfusion (I/R) injury by regulating miR-6322/PARP2 signaling pathway. MATERIALS AND METHODS: Cell viability was checked by CCK-8; LDH concentration, ROS production, MDA, SOD and GSH-Px were measured by corresponding kits; QPCR was used to inspect the expression of circRNA-0068566 and miR-6322 in I/R injury and H9C2 cells; luciferase reporter assay confirmed the direct target effect of circRNA-0068566 and miR-6322; Western blot was used to investigate PARP2 protein expression in I/R injury and H9C2 cells. RESULTS: We analyzed the regulatory effect of circRNA-68566 on I/R injury and found that circRNA-68566 promoted the proliferation of injured cardiomyocytes in vitro and in vivo. circRNA-68566 and miR-6322 were directly combined to regulate the development of I/R injury. We also confirmed that PARP2 was the target of miR-6322 in I/R injury. CONCLUSIONS: We believed that circRNA-68566 participated in myocardial ischemia-reperfusion injury by regulating miR-6322/PARP2 signaling pathway, which provided a new possible strategy for the treatment of I/R injury.
Asunto(s)
MicroARNs/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , ARN Circular/metabolismo , Transducción de Señal , Animales , Línea Celular , Masculino , Ratones , RatasRESUMEN
The rare complications of cirrhosis, such as chylous ascites, hepatic hydrothorax, spontaneous bacterial peritonitis, cirrhotic cardiomyopathy, portopulmonary hypertension, cirrhotic nervous system damage, etc., have not yet been fully understood and/or promptly and effectively diagnosed and treated by clinicians. Therefore, this article aims to introduce the above-mentioned rare complications, clinical features, treatment and prognosis of liver cirrhosis in an attempt to improve the clinicians' understanding and level of diagnosis and treatment.
Asunto(s)
Infecciones Bacterianas , Hidrotórax , Cirrosis Hepática , Peritonitis , Ascitis/etiología , Infecciones Bacterianas/etiología , Humanos , Hidrotórax/etiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/terapia , Peritonitis/etiología , PronósticoRESUMEN
OBJECTIVE: Histidine-Rich Glycoprotein (HRG) has been reported to be associated with idiopathic pulmonary fibrosis, cancer, and sepsis as a novel biomarker. However, there is limited evidence regarding its value in diagnosing or prognosis evaluating of ventilator-associated pneumonia (VAP). PATIENTS AND METHODS: A total of 186 patients intubated in ICU and 65 healthy volunteers were enrolled in this study. Patients were divided into VAP group (n = 116), non-VAP group (n = 70) and control group (n = 65). The HRG, C reactive protein (CRP) and procalcitonin (PCT) levels were measured 72 hours after intubation, while blood sample was acquired from healthy controls for the test. RESULTS: HRG of VAP group was significantly lower than non-VAP group and control group (p < 0.001), while CRP and PCT were significantly higher (p < 0.001). The ROC analysis showed that the AUC of HRG was 0.777 95% CI (0.708-0.847) with a cut-off value of 38.55 µg/mL, which was lower than CRP [AUC = 0.912, 95% CI (0.847-0.950)] and PCT [AUC = 0.818, 95% CI (0.759-0.876)]. No linear correlation was found between HRG and CRP, as well as PCT (p > 0.05). However, the survival analysis showed that patients with higher level of HRG had a significantly higher survival rate (p < 0.001). The multivariate Cox regression analysis also demonstrated that the higher level of HRG was associated with better survival [HR 0.290, 95% CI (0.131-0.641), p = 0.002]. CONCLUSIONS: Serum HRG decreases when the patient develops VAP, which might be used as a biomarker for the diagnosis of VAP, with relatively less accuracy than PCT and CRP. However, HRG is valuable in predicting the clinical outcomes of mechanical ventilation patients.
Asunto(s)
Neumonía Asociada al Ventilador/diagnóstico , Proteínas/metabolismo , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Calcitonina/sangre , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Neumonía Asociada al Ventilador/sangre , Polipéptido alfa Relacionado con Calcitonina/sangre , Pronóstico , Estudios Prospectivos , Precursores de Proteínas/sangre , Curva ROC , Respiración Artificial/efectos adversos , Tasa de SupervivenciaRESUMEN
Objective: To investigate the clinical features and risk factors for acute kidney injury (AKI) in patients with cirrhosis. Methods: A total of 1 165 hospitalized patients with chronic liver diseases were enrolled. Among them, 94 patients had chronic hepatitis, while 1 071 patients were diagnosed as cirrhosis. The clinical data, renal and liver function were retrospectively analyzed. AKI was determined according to the criteria proposed by International Club of Ascites. Compared with chronic hepatitis group, the clinical features and risk factors for AKI in patients with cirrhosis were evaluated using logistic regression. Results: The prevalence of AKI in chronic hepatitis and cirrhosis were 4.26%(4/94) and 11.11% (119/1 071), respectively. The AKI rates in patients with liver function Child A, B and C were 3.77%(18/377), 10.88% (41/377) and 27.65%(60/217), respectively. The independent risk factors for AKI in cirrhotic patients included infections (OR=5.37, 95%CI 3.24-8.90, P=0.000), acute on chronic liver failure (ACLF, OR=4.55, 95%CI 2.60-7.98, P=0.000) and diabetes (OR=1.70, 95%CI 1.07-2.70, P=0.024). The mortality rate of cirrhotic patients with AKI was 36.97% within 2 months. Moreover, the mortality rates in stage â , â ¡ and â ¢ AKI were 20.31%, 36.00% and 73.33%, respectively. Conclusions: The mortality rate of cirrhotic patients with stage â ¢ AKI is extremely high. Infections, ACLF and diabetes are the independent risk factors for AKI in patients with cirrhosis.
Asunto(s)
Lesión Renal Aguda/epidemiología , Insuficiencia Hepática Crónica Agudizada/epidemiología , Cirrosis Hepática/epidemiología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/mortalidad , Insuficiencia Hepática Crónica Agudizada/complicaciones , Insuficiencia Hepática Crónica Agudizada/mortalidad , China/epidemiología , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/mortalidad , Prevalencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Liver fibrosis and cirrhosis, is a chronic, occult progression that is potentially reversible and complicated. The hepatic venous pressure gradient is a "gold standard" for risk stratification of liver cirrhosis and is superior to pathological examination of liver. This article briefly assesses the invasive and non-invasive measuring methods of the hepatic venous pressure gradient. With the hepatic venous pressure gradient-guided precise treatment for hepatic cirrhosis of portal hypertension, the incidence of clinical endpoints of hepatic portal hypertension can be significantly reduced. Establishing a long-term monitoring and management model similar to "high blood pressure" is a dream for the diagnosis and treatment of future cirrhosis and portal hypertension.
Asunto(s)
Hipertensión Portal/diagnóstico , Hipertensión Portal/tratamiento farmacológico , Cirrosis Hepática , Presión Portal , Presión Venosa , Fibrosis , Venas Hepáticas/fisiopatología , Humanos , Cirrosis Hepática/complicacionesRESUMEN
The activation of renin-angiotensin-aldosterone-vasopressin system is a key factor in the formation of ascites due to splanchnic vasodilation in cirrhosis. In theory, aldosterone antagonists, contraction of blood vessels, vasopressin V2 receptor, and angiotensin receptor antagonists are important targets for the prevention and treatment of cirrhotic ascites. The 15%-20% of patients with cirrhotic ascites that show no response to at least one week's treatment with potent diuretics (spironolactone 160 mg/d combined with furosemide 80 mg/d) are considered to have refractory ascites. At present, effective treatments for refractory ascites include tolvaptan, large-volume paracentesis (4000-6000 ml/time/day) combined with albumin (4 g/L ascites), ascites ultrafiltration and reinfusion, transjugular intrahepatic portosystemic shunt, and liver transplantation. In the future, with the development of vasoactive drugs, rifaximin, ascites drainage pump, and other new therapies, the treatment of refractory ascites may be more effective to reduce the need for liver transplantation.
Asunto(s)
Ascitis/diagnóstico , Ascitis/terapia , Diuréticos/uso terapéutico , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/terapia , Paracentesis , Derivación Portosistémica Intrahepática Transyugular , Albúminas/administración & dosificación , Ascitis/etiología , Fibrosis , Humanos , Cirrosis Hepática/complicaciones , Trasplante de Hígado , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Sistema Renina-Angiotensina , Rifamicinas , Rifaximina , Resultado del TratamientoRESUMEN
Objective: To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression. Methods: Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment. Results: A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness. Conclusion: This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.
Asunto(s)
Hepatitis B Crónica/patología , Cirrosis Hepática/patología , Hígado/patología , Alanina Transaminasa/sangre , Antivirales/uso terapéutico , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/tratamiento farmacológicoRESUMEN
There are two common types of hereditary polycystic kidney diseases, autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease. Congenital hepatic fibrosis is an autosomal recessive disorder and can occur in hereditary polycystic kidney disease. Therefore, hereditary polycystic kidney disease is one of the causes of unexplained liver fibrosis and liver cirrhosis.
Asunto(s)
Enfermedades Genéticas Congénitas , Cirrosis Hepática/etiología , Enfermedades Renales Poliquísticas , Riñón Poliquístico Autosómico Dominante , Humanos , Enfermedades del Sistema Nervioso PeriféricoRESUMEN
BACKGROUND: The prognosis of patients with hepatocellular carcinoma(HCC) is generally very poor with a 5-year survival rate of less than 15% since most of them are diagnosed clinically at their late stage. However, the differential diagnosis between alpha fetoprotein(AFP) negative HCC and cirrhotic nodules is still difficult. OBJECTIVES: To evaluate the diagnostic value of glypican-3(GPC3) in patients with AFP negative hepatitis B related HCC. METHODS: The liver tissue GPC3 (GPC3L) expression was tested from 426 for surgery and 179 of needle biopsies of hepatitis B related HCC patients using immunohistochemistry staining. Serum GPC3 (GPC3S) and AFP were also measured. RESULTS: Among surgical HCC samples, 80.0% of GPC3L expression was positive, however, in paracarcinomatous and cirrhotic nodules were negative. In needle biopsy tissues, GPC3L positively expression was in 74.9%. The sensitivity of AFP>400 µg/L was 25.4%. The GPC3S >3.5 µg/L was determined as a positive. The area of ROC curve of GPC3S was 0.68(95% CI 0.56-0.79,P<0.05) in all HCC patients,0.81 (95% CI 0.62 -0. 98, P<0.05) in AFP greater or equal to 400 µg/L and 0.64 (95% CI 0.51-0.77, P=0.051) in AFP negative patients. The GPC3S was positive in 48.8% of patients with AFP negative. No difference was observed between GPC3L/GPC3S and serum AFP. CONCLUSIONS: GPC3 may be helpful in improving diagnosis of HCC and in differentiating diagnosis between AFP negative HCC and cirrhotic nodules.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma Hepatocelular/diagnóstico , Glipicanos/sangre , Cirrosis Hepática , Neoplasias Hepáticas/diagnóstico , alfa-Fetoproteínas/análisis , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Carcinoma Hepatocelular/química , China , Diagnóstico Diferencial , Femenino , Hepatitis B/sangre , Humanos , Cirrosis Hepática/sangre , Neoplasias Hepáticas/química , Masculino , Persona de Mediana EdadRESUMEN
AIMS/HYPOTHESIS: The content of heparan sulphate is reduced in the endothelium under hyperglycaemic conditions and may contribute to the pathogenesis of atherosclerosis. Heparanase-1 (HPR1) specifically degrades heparan sulphate proteoglycans. We therefore sought to determine whether: (1) heparan sulphate reduction in endothelial cells is due to increased HPR1 production through increased reactive oxygen species (ROS) production; and (2) HPR1 production is increased in vivo in endothelial cells under hyperglycaemic and/or atherosclerotic conditions. METHODS: HPR1 mRNA and protein levels in endothelial cells were analysed by RT-PCR and Western blot or HPR1 enzymatic activity assay, respectively. Cell surface heparan sulphate levels were analysed by FACS. HPR1 in the artery from control rats and a rat model of diabetes, and from patients under hyperglycaemic and/or atherosclerotic conditions was immunohistochemically examined. RESULTS: High-glucose-induced HPR1 production and heparan sulphate degradation in three human endothelial cell lines, both of which were blocked by ROS scavengers, glutathione and N-acetylcysteine. Exogenous H(2)O(2) induced HPR1 production, subsequently leading to decreased cell surface heparan sulphate levels. HPR1 content was significantly increased in endothelial cells in the arterial walls of a rat model of diabetes. Clinical studies revealed that HPR1 production was increased in endothelial cells under hyperglycaemic conditions, and in endothelial cells and macrophages in atherosclerotic lesions. CONCLUSIONS/INTERPRETATION: Hyperglycaemia induces HPR1 production and heparan sulphate degradation in endothelial cells through ROS. HPR1 production is increased in endothelial cells from a rat model of diabetes, and in macrophages in the atherosclerotic lesions of diabetic and non-diabetic patients. Increased HPR1 production may contribute to the pathogenesis and progression of atherosclerosis.