Betacoronavirus ; isolation & purification ; pathogenicity ; Bile Acids and Salts ; metabolism ; Bile Ducts, Intrahepatic ; pathology ; virology ; Cell Culture Techniques ; Coronavirus Infections ; complications ; pathology ; Cytokine Release Syndrome ; etiology ; physiopathology ; Cytopathogenic Effect, Viral ; Epithelial Cells ; enzymology ; pathology ; virology ; Humans ; Hyperbilirubinemia ; etiology ; Liver ; pathology ; Organoids ; pathology ; virology ; Pandemics ; Peptidyl-Dipeptidase A ; analysis ; Pneumonia, Viral ; complications ; pathology ; Receptors, Virus ; analysis ; Serine Endopeptidases ; analysis ; Viral Load

BACKGROUND/AIMS: Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL). METHODS: The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E) staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs) treated with lithocholic acid (LCA) and siRNA-CRP. RESULTS: The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP. CONCLUSION: CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.
Angiogenic Proteins/genetics/metabolism ; Animals ; Bile Ducts/surgery ; C-Reactive Protein/*analysis/genetics/metabolism ; Cells, Cultured ; Disease Models, Animal ; Hepatic Veins/abnormalities ; Hepatocytes/cytology/metabolism ; Human Umbilical Vein Endothelial Cells ; Humans ; Lithocholic Acid/pharmacology ; Liver/metabolism/pathology ; Liver Cirrhosis/etiology ; Liver Diseases/metabolism/*pathology ; Male ; Microscopy, Fluorescence ; Mitochondria/drug effects/metabolism ; RNA Interference ; RNA, Small Interfering/metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Serum Albumin/genetics/metabolism

No abstract available.
Bile Ducts, Intrahepatic ; Cell Differentiation ; Cholangiocarcinoma/*pathology ; Humans ; Immunohistochemistry ; Keratin-19/metabolism ; Liver Neoplasms/*pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Tomography, X-Ray Computed

No abstract available.
Adenoma, Liver Cell/*diagnosis/diagnostic imaging/pathology ; Aged ; Antigens, CD34/metabolism ; Bile Ducts, Intrahepatic/pathology ; C-Reactive Protein/metabolism ; Female ; Humans ; Liver Neoplasms/*diagnosis/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Serum Amyloid A Protein/metabolism ; Tomography, X-Ray Computed

A 51-year-old male patient with chronic hepatitis B was referred to our hospital due to a 1-cm liver nodule on ultrasonography. Alpha-fetoprotein (AFP) was slightly elevated. The nodule showed prolonged enhancement on dynamic liver magnetic resonance imaging and appeared as a hyperintensity on both diffusion-weighted and T2-weighted imaging. The nodule was followed up because it was small and typical findings of hepatocellular carcinoma (HCC) were not observed in the dynamic imaging investigations. However, liver contrast-enhanced ultrasonography performed 1 month later showed enhancement during the arterial phase and definite washout during the delayed phase. Also, AFP had increased to over 200 ng/mL even though AST and ALT were decreased after administering an antiviral agent. He was presumptively diagnosed as HCC and underwent liver segmentectomy. Microscopy findings of the specimen indicated bile duct adenoma. After resection, the follow-up AFP had decreased to within the normal range. This patient represents a case of bile duct adenoma with AFP elevation mimicking HCC on contrast-enhanced ultrasonography.
Bile Duct Neoplasms/*complications/*diagnosis/pathology ; *Bile Ducts, Intrahepatic ; Hepatitis B, Chronic/*complications/*diagnosis/pathology ; Humans ; Liver/pathology/ultrasonography ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Tomography, X-Ray Computed ; alpha-Fetoproteins/*metabolism

BACKGROUND/AIMS: To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing. METHODS: An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay. RESULTS: The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA led to significantly decreased NI (p<0.05) and slightly decreased cell proliferation. CONCLUSIONS: CXCR4 is likely correlated with clinical recurrence of hilar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA.
Aged ; Bile Duct Neoplasms/metabolism/*pathology ; Bile Ducts, Intrahepatic/metabolism/*pathology ; Case-Control Studies ; Cell Line, Tumor ; Cell Proliferation ; Cholangiocarcinoma/metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/metabolism/pathology ; RNA Interference/*physiology ; RNA, Small Interfering/metabolism ; Receptors, CXCR4/antagonists & inhibitors/*metabolism ; Tumor Cells, Cultured

No abstract available.
Aged ; Bile Duct Neoplasms/metabolism/*pathology ; Bile Ducts, Intrahepatic/metabolism/*pathology ; Cholangiocarcinoma/metabolism/*pathology ; Humans ; Immunohistochemistry ; Keratin-19/metabolism ; Male ; Positron-Emission Tomography ; Tomography, X-Ray Computed

OBJECTIVETo study the correlation between clinicopathological features and serum carbohydrate antigen 19-9 (CA19-9)/carcinoembryonic antigen (CEA) in patients with extrahepatic cholangiocarcinoma (ECC).

METHODSThe clinicopathological data of 126 cases of extrahepatic cholangiocarcinoma treated in our department from Jan. 1999 to Dec. 2012 were collected and analyzed in this study. The correlation between clinicopathological features and sensitivity of CA19-9/CEA was analyzed by chi-square test. The correlation of clinicopathological features and value of serum CA19-9/CEA was analyzed by t test and F test.

RESULTSThe average value of CA19-9 before surgery in the 126 patients was 595.3 U/ml. The values of CA19-9 in 91 patients were abnormal and the sensitivity of CA19-9 was 72.2%. The average value of CEA before surgery was 12.6 U/ml. The value of CEA in 26 patients were abnormal and the sensitivity of CEA was 20.6%. The values of combined detection of serum CA19-9 and CEA before surgery were abnormal in a total of 97 cases with a sensitivity of 77.0%. There was no significant correlation between clinicopathological features and sensitivity of CA19-9 (P > 0.05). The location of tumor was significantly correlated to the diagnostic sensitivity of CEA. The sensitivity of CEA to distal ECC was only 15.4%. The value of CA19-9 was relatively high in patients >60-year old or with neural invasion, while CEA was higher when tumor was located in the middle of bile duct (P < 0.05). There was no significant difference of serum CA19-9 before and after jaundice reduction (P > 0.05).

CONCLUSIONSThe diagnostic sensitivity of CA19-9 is not affected by gender, age, blood type, tumor location, degree of differentiation, tumor size, T stage, vascular tumor thrombus, lymph node metastasis, perineural invasion, and preoperative jaundice. However, the diagnostic sensitivity of CEA is affected by tumor location. The value of CA19-9 is correlated with tumor invasion and is relatively high in patients above 60 years old.

Bile Duct Neoplasms ; metabolism ; pathology ; Bile Ducts, Intrahepatic ; metabolism ; pathology ; Biomarkers, Tumor ; metabolism ; CA-19-9 Antigen ; metabolism ; Carcinoembryonic Antigen ; metabolism ; Cholangiocarcinoma ; metabolism ; pathology ; Humans ; Lymphatic Metastasis

OBJECTIVETo investigate the role of absent ductular reaction (DR) at hepatocellular-stromal boundaries in early stage hepatocellular carcinoma (HCC) with cirrhosis in patients with chronic hepatitis B.

METHODSCytokeratin (CK)7 and CK19 expression was detected by the SP immunohistochemistry method in 112 hepatic nodules taken from 20 cases of early HCC, 26 cases of HCC with nodules more than 3 cm, 20 cases of high-grade dysplastic nodule (HGDN), 26 cases of low-grade dysplastic nodule (LGDN), and 20 cases of cirrhosis (CIR). DR/CK7 and DR/CK19 were assessed separately on a semi-quantitative scale and statistically analyzed.

RESULTSThe mean age of the patients in the study was 53.71 years-old, and the study population consisted of 73 males and 39 females. The follow-up time ranged from 3 to 90 months. Positive CK7 and CK19 staining was detected in the cytoplasm of DR-positive hepatobiliary cells, interlobular bile duct, and a portion of hepatic cells. All of the DR/CK7- and DR/CK19-positive cells were localized around the non-invasive nodules. Specimens with focal or diffuse DR/CK7- and DR/CK19-loss had more robust stromal invasion. Specimens from early HCC cases showed greater DR/CK19 loss than specimens from HGDN cases, LGDN cases and CIR cases (all P less than 0.01). DR/CK7 loss of early HCC was less than HCC with nodules more than 3 cm (P less than 0.05), and more than LGDN cases and CIR cases (both P less than 0.01).The area under the receiver operating characteristic curve of DR/CK7 was very similar to that of DR/CK19 (P more than 0.05). Pearson's correlation analysis indicated that DR/CK7 and DR/CK19 were positively correlated with tumor-free time (P less than 0.01) and negatively correlated with early recurrence time as well as death rate (both P less than 0.01). Furthermore, cases showing DR/CK7 or DR/CK19 loss had lower overall survival rate and tumor-free survival rate (P less than 0.01) and higher early recurrence rate (P less than 0.01).

CONCLUSIONDR/CK7 and DR/CK19 immunostaining may help to distinguish non-invasive HGDNs from both minimally-invasive and overtly-invasive HCCs by identifying small foci of invasion and predicting increased risk of invasiveness.

Adult ; Aged ; Aged, 80 and over ; Bile Ducts, Intrahepatic ; pathology ; Carcinoma, Hepatocellular ; diagnosis ; pathology ; virology ; Early Diagnosis ; Female ; Hepatitis B, Chronic ; pathology ; Humans ; Immunohistochemistry ; Keratin-19 ; metabolism ; Keratin-7 ; metabolism ; Liver Neoplasms ; diagnosis ; pathology ; virology ; Male ; Middle Aged

OBJECTIVETo explore the inhibitory effect of angiotensin (1-7) on hepatic sinusoid angiogenesis using a rat model of hepatic fibrosis.

METHODSEighteen male Wistar rats were randomly divided into three equal groups for sham operation (untreated/uninduced control group), bile duct ligation (BDL) (untreated model group), or BDL with angiotensin (1-7) treatment (treated model group). Histological analysis was used to assess the liver fibrosis score, by hematoxylin-eosin staining, and the level of fibrosis, by Masson's trichrome staining. Immunohistochemistry, western blotting, and immunofluorescence were used to assess the expression of the angiogenesis markers vWF, VEGFA, and CD31.

RESULTSCompared with the untreated/uninduced control group, the untreated BDL model group showed remarkably higher fibrosis score, area of the type I collagen expression, and expression levels of vWF, VEGFA, and CD31. However, the angiotensin (1-7)-treatment protected against the BLD-related changes, as evidenced by decreased robustness and down-regulation of the corresponding indicators. Moreover, the expression level of VEGFA was highly correlated to the expression level of vWF (r = 0.956, P = 0.000).

CONCLUSIONBDL-induced hepatic fibrosis is accompanied by significant increases in angiogenesis-related factors, but angiotensin (1-7) treatment may inhibit hepatic sinusoid angiogenesis during the liver fibrosis process.

Angiotensin I ; therapeutic use ; Animals ; Bile Ducts ; surgery ; Hepatic Veins ; pathology ; Ligation ; Liver Cirrhosis, Experimental ; drug therapy ; pathology ; Male ; Neovascularization, Pathologic ; drug therapy ; Peptide Fragments ; therapeutic use ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Rats ; Rats, Wistar ; Vascular Endothelial Growth Factor A ; metabolism ; von Willebrand Factor ; metabolism