Degeneration Of Liver Cells Research Articles

The Effect of Ethanol Extract Mymercodia pendans on Paracetamol-Induced Hepatotoxicity in White Rats

The present study was investigate the hepatoprotective effect of ethanol extract Mymercodia pendans(EEMP) in white rats. Hepatotoxicity was induced in rats by oral administration of Paracetamol (PCM) 250 mg/kg/d for ten days. Effect of concurrent administration of EEMP at a dose of 250 mg/kg/d given by oral route was determined using aspartate transaminase (AST), alanine transaminase (ALT) and histological paramater as indicators of hepar damage. The results showed that ethanol extract of M. pendans resulted in significant (p<0.05) decrease in paracetamol-induced by increasing levels of liver enzymes. Histopathologic examination revealed that PCM administration produced liver cell necrosis, degeneration, hemorrhage and congestion, but the degree of induced hepatotoxicity-paracetamol was reduce by treatment with EEMP. This can be concluded that ethanolic extract of M. pendans possess hepatoprotective activity.

Protective effects of rutin on liver injury in type 2 diabetic db/db mice

The aim of this study was to evaluate the protective effect of rutin on the liver of type 2 diabetic mice and explore the correlation mechanism. The db/db mice, selected as the type 2 diabetes mellitus (T2DM) models, have random blood glucose (RBG) and glucose level after 2 h of oral glucose loading of more than 16.7 mmol/L. After administration of 120 mg/kg or 60 mg/kg rutin, to T2DM mice, RBG, oral glucose tolerance, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, and advanced glycation end products (AGEs) in vivo and vitro of different groups were detected. The liver pathological changes were observed under light and electron microscopy. Western blotting was used to detect the protein expression of insulin receptor substrate 2 (IRS-2) and phosphorylation of phosphatidylinositol 3 kinase (PI3K) on p85, Akt on Ser473, glycogen synthase kinase 3β (GSK-3β) on Ser9, real-time quantitative PCR was used to detect IRS-2 mRNA expression. Moreover, dynamically observing the effect of rutin on the generation of AGEs in non-enzymatic protein glycosylated system, Cell Counting Kit-8 (CCK-8) method was used to detect the effect of rutin on proliferation activity of HepG2 liver cells. The results showed that RBG and glucose levels of oral glucose tolerance test (OGTT) of mice in model group were significantly higher than that of normal group, which were significantly reduced after the rutin treatment. Rutin could reduce the ALT, AST activities and AGEs level in serum and potentiate the expression of IRS-2, P-PI3K (p85), P-Akt (Ser473), P-GSK-3β (Ser9) protein and IRS-2 mRNA in the liver tissue of db/db mice. Moreover, rutin could significantly alleviate the structure disorder of liver, reduce the degeneration and necrosis of liver cells and formation of collagen fibers of db/db mice. The results in vitro also showed that rutin could obviously inhibit the generation of AGEs, and promoted the proliferation activity of high glucose-stimulating HepG2 cells. In general, the protective effect of rutin on the liver of T2DM may be mediated by facilitating signal transduction and activated state of insulin IRS-2/PI3K/Akt/GSK-3β signal pathway, promoting hepatocyte proliferation, reducing blood glucose level and generation of AGEs.

Progress in non-invasive detection of liver fibrosis.

Liver fibrosis is an important pathological precondition for hepatocellular carcinoma. The degree of hepatic fibrosis is positively correlated with liver cancer. Liver fibrosis is a series of pathological and physiological process related to liver cell necrosis and degeneration after chronic liver injury, which finally leads to extracellular matrix and collagen deposition. The early detection and precise staging of fibrosis and cirrhosis are very important for early diagnosis and timely initiation of appropriate therapeutic regimens. The risk of severe liver fibrosis finally progressing to liver carcinoma is >50%. It is known that biopsy is the gold standard for the diagnosis and staging of liver fibrosis. However, this method has some limitations, such as the potential for pain, sampling variability, and low patient acceptance. Furthermore, the necessity of obtaining a tissue diagnosis of liver fibrosis still remains controversial. An increasing number of reliable non-invasive approaches are now available that are widely applied in clinical practice, mostly in cases of viral hepatitis, resulting in a significantly decreased need for liver biopsy. In fact, the non-invasive detection and evaluation of liver cirrhosis now has good accuracy due to current serum markers, ultrasound imaging, and magnetic resonance imaging quantification techniques. A prominent advantage of the non-invasive detection and assessment of liver fibrosis is that liver fibrosis can be monitored repeatedly and easily in the same patient. Serum biomarkers have the advantages of high applicability (>95%) and good reproducibility. However, their results can be influenced by different patient conditions because none of these markers are liver-specific. The most promising techniques appear to be transient elastography and magnetic resonance elastography because they provide reliable results for the detection of fibrosis in the advanced stages, and future developments promise to increase the reliability and accuracy of the staging of hepatic fibrosis. This article aims to describe the recent progress in the development of non-invasive assessment methods for the staging of liver fibrosis, with a special emphasize on computer-aided quantitative and deep learning methods.

The hepatoprotective role of reduced glutathione and its underlying mechanism in oxaliplatin-induced acute liver injury

Currently, the underlying mechanism of oxaliplatin (OXA) induced live injury is unclear. In addition, there is no standard clinical treatment for OXA-induced acute liver injury (ALI). In this study, we established an animal model of OXA-induced ALI, and studied the role of oxidative stress in OXA-induced ALI and the impacts of reduced glutathione (GSH) treatment on OXA-induced ALI. To establish an OXA-induced ALI model, KM mice received intraperitoneal injection of OXA (8 mg/kg) for 4 days. Serum alanine aminotransferase (ALT), aspartate aminotransferase levels (AST), hepatic pathology and oxidative stress indicators in liver tissues were analyzed. To study the impact of GSH treatment on OXA-induced ALI, mice were treated with GSH (400 mg/kg, i.p). In this ALI mouse model, ALT and AST levels were significantly increased (P<0.01). Liver pathological examination revealed varying degrees of liver cell turbidity and degeneration, even balloon-like changes and focal necrosis, and sinusoidal hemorrhage in some cells. Compared with control group, the malondialdehyde (MDA) and GSH levels were significantly increased in OXA-treated group (P<0.01), while the superoxide dismutase SOD and GSH-peroxidase levels were decreased after OXA withdrawal (P<0.01). When GSH was used to treat OXA-induced ALI mice, the pathological injury of liver tissues was alleviated, and serum ALT and AST were significantly decreased. In addition, GSH treatment could reduce the OXA-induced increase of MDA level (P<0.05) in liver tissues, but had no impact on SOD level (P>0.05). We have successfully established an OXA-induced ALI model. Using this model, we discover that oxidative stress plays an important role in OXA-induced ALI. GSH-based hepatoprotective therapy can partially inhibit oxidative stress and alleviate OXA-induced ALI.

Acute Toxicity Tests of Alkaloid Pare (Momordica Charanthia) Fruit on The Histopathology of Liver

Pare fruit (Momordica charanthia) potential as an antidiabetic. In preliminary research has proven that alkaloid of the Pare fruit (Momordica charanthia) can lower blood sugar levels of mice suffering from diabetes mellitus. Alkaloid Pare can improve pancreatic β-cell function by improving the preparation phase for the cell dividing (interphase) and repair the mitotic stages and increase the CDK expression in mice with diabetes mellitus. The purpose of this research was to determine the dose that causes the death of 50% (LD50) and to determine the toxicity effect of alkaloid Pare (Momordica charanthia) against damage in the form of congestion, degeneration, and necrosis of liver cells. Acute toxicity test with a 24-hour long treatment using 60 female mice, divided into six groups, each group consisted of 10 animals. The group is as follows: P0 only given distilled water, the group P1, P2, P3, P4 and P5 respectively treated 0.3 g/kg bw, 1 g/kg bw, 3 g/kg bw, 10 g/kg bw and 15 g/kg bw. Furthermore, all the mice were necropsied to take the liver for histopathology preparations to observe the occurrence of congestion, degeneration, and necrosis. The parameters observed through histopathological examination of the liver include congestion, degeneration, and necrosis. The results of the research tested by Kruskal-Wallis test with data obtained based on the value of scoring was not significantly different (α&lt;0.05) in the liver histopathological changes in the form of congestion, degeneration, and necrosis between control and treatment groups orally in time 24 hours. The dose can cause 50% of deaths more than 15 g in mice are included in the category of medicinal substances which are not harmful. Keywords: Alkaloid Pare fruit, LD50, congestion, degeneration, necrosis, liver.

A Comparative Study of Pseudocholinesterase Activities in Relation to Transaminases, GGT and ALP in Liver Disorder in Hospital Based Study

Objective: To compare pseudocholinesterase activities in relation to transaminases, GGT and ALP in liver diseases. Method: A prospective study was conducted at College of Medical Sciences –Teaching Hospital (CMS-TH), from May 2011 to May 2013 with 25 healthy (controls) and 25 diagnosed cases each of carcinoma of liver, cirrhosis of liver, infective hepatitis and obstructive jaundice among both sexes of same age group attending medical outpatient and inpatient departments. Serum pseudocholinesterase and other liver function test parameters were performed with semi - autoanalyzer and Roche Hitachi 902 respectively. Result: Pseudocholinesterase level was significantly decrease in the order of control (mean ± SD = 6865.12 ± 928.41) > obstructive jaundice (mean ± SD = 5539 ± 791.05) > infective hepatitis (mean ± SD = 3800.69 ± 764.17) > cirrhosis of liver (mean ± SD = 1735.16 ± 433.82) > carcinoma of liver (mean ± SD = 1369.48 ± 276.64). The difference in the means was statistically significant (p<0.001). Similarly aspartate transaminase (AST) (Mean ± SD= 311.48 ± 177.15) and alanine transaminase (ALT) (Mean ± SD = 491.36 ± 308.92) were higher in hepatitis but in carcinoma of liver the AST (Mean ± SD = 292.55 ± 92.85) level was higher than ALT (Mean ± SD = 179.24 ± 70.25). The difference in the means was statistically significant (p<0.001). AST level was 1.6 time higher than ALT. alkaline phosphatase (ALP) (Mean ± SD = 419.39 ± 90.49) and gamma glutamyl transaminase (GGT) (Mean ± SD = 257.81 ± 68.29) level were higher in obstructive jaundice and GGT (Mean ± SD = 195.54 ± 107.75) level was found to be higher in carcinoma of liver. The difference in the means was statistically significant (p<0.001) Conclusion: There was significant decrease in pseudocholinesterase level in carcinoma of liver followed by cirrhosis of liver and less so in infective hepatitis. AST and ALT level were higher in hepatitis cases. The level of AST was found higher in carcinoma of liver than ALT. In obstructive jaundice ALP and GGT was raised and statistically significant. GGT level was raised in carcinoma of liver. Pseudocholinesterase level was found to be normal in obstructive jaundice. The study results indicated that with more severe liver cell destruction or cell degeneration, there was corresponding significant decrease in the level of pseudocholinesterase, which could be used as diagnostic marker of liver disease.

Role of complement regulatory protein CD55 in the liver immune injury of trichloroethylene-sensitized mice

Objective: To explore the expression of CD55 in liver tissue of trichloroethylene-sensitized mice and discuss the role of CD55 in the liver immune injury of trichloroethylene-sensitized mice. Methods: 6-8 weeks specific pathogen free female BALB/c were randomly divided into blank control group, solvent control group and TCE treatment group to establish BALB/c mice sensitized model. According to mouse skin sensitization reaction score, TCE treatment mice were divided into sensitized and non-sensitized group at 24 h after the last challenge. At 48 h after the last challenge, the blood and aseptic livers were collected. The level of serum ALT was tested by automatic biochemical analyzer and pathology of the liver was observed. C5b-9 deposition was studied by immunohistochemistry (IHC) . CD55 protein expression level in liver tissue was studied by immunohistochemistry and Western blotting. The expression of CD55 mRNA in liver tissue was detected by qRT-PCR. Results: Liver function test result showed level of serum ALT in TCE sensitized group was significantly higher than solvent control group and TCE non-sensitized group (P<0.05) . There was ballooning degeneration and necrosis of liver cells in TCE sensitized group. IHC demonstrated that TCE sensitized group had obviously increased content of C5b-9 but had reduced content of CD55 compared with solvent control group and TCE non-sensitized group (P<0.05) . Western blotting also showed that TCE sensitized group had lower expression of CD55 than solvent control group and TCE non-sensitized group (P<0.05) . qRT-PCR showed that CD55 mRNA expression level in liver tissue of TCE sensitized group was apparently lower than solvent control group and TCE non-sensitized group (P<0.05) . Conclusion: Complement activation may be involved in TCE-induced liver injury, and the expression change of complement regulatory protein CD55 may play essential role in the process.

Chapter 7 - Wilson disease – liver pathology

The liver in Wilson disease may demonstrate a wide range of damage patterns. Some patients may present almost no detectable microscopic pathology, while others display lesions consistent with fulminant hepatitis or acute liver failure. Most liver biopsy specimens show moderate to severe steatosis, variable degree of portal and/or lobular inflammation, and fibrosis eventually progressing to cirrhosis. Additional findings include liver cell degeneration and ballooning, Mallory hyaline bodies, liver cell necrosis, and glycogenation of periportal hepatocytic nuclei. None of the above lesions are specific for Wilson disease and should be interpreted in a wider medical context and particular clinical setting. The main message concerning liver pathology is that Wilson disease may be microscopically misinterpreted as many other liver diseases, including viral or autoimmune hepatitis, alcoholic/nonalcoholic steatohepatitis, toxic liver injury, cryptogenic cirrhosis, metabolic liver disease, and many others. The possibility of Wilson disease should be considered in all patients, especially young ones presenting unexplained liver diseases with many variable patterns of microscopic liver involvement.

Schisandra polysaccharide inhibits hepatic lipid accumulation by downregulating expression of SREBPs in NAFLD mice.

BackgroundHepatoprotective effects of Chinese herbal medicine Schisandra Chinensis (Schisandra) have been widely investigated. However, most studies were focused on its lignan extracts. We investigated the effects of Schisandra polysaccharide (SCP) in a mouse model of non-alcoholic fatty liver disease (NAFLD), and studied its effect on sterol regulatory element binding proteins (SREBPs) and the related genes.MethodsThe mouse model of NAFLD was established by feeding mice with a high-fat diet for 16 weeks. Effect of SCP-treatment (100 mg/kg, once daily for 12 weeks) on biochemical parameters and liver histopathology was assessed. Relative levels of sterol regulatory element-binding proteins (SREBPs) and their gene expressions were determined by quantitative real-time polymerase chain reaction and Western Blot.ResultsSCP significantly reduced the liver index by 12.0%. Serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol, alanine aminotransferase and aspartate aminotransferase were decreased by 31.3, 28.3, 42.8, 20.1 and 15.5%, respectively. Serum high-density lipoprotein cholesterol was increased by 26.9%. Further, SCP lowered hepatic TC and TG content by 27.0% and 28.3%, respectively, and alleviated fatty degeneration and necrosis of liver cells. A significant downregulation of mRNA and protein expressions of hepatic lipogenesis genes, SREBP-1c, fatty acid synthase and acetyl-CoA carboxylase, and the mRNA expression of liver X receptor α (LXRα) was observed in NAFLD mice treated with SCP. SCP also significantly reduced the hepatic expression of SREBP-2 and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR).ConclusionThese findings demonstrate the hepatoprotective effects of SCP in a mouse model of NAFLD; the effects may be mediated via downregulation of LXRα/SREBP-1c/FAS/ACC and SREBP-2/HMGCR signaling pathways in the liver.

Clinical analysis and follow-up of neonatal intrahepatic cholestasis caused by Citrin deficiency in 29 children

Objective To analyze the main clinical manifestations, laboratory features and prognosis of neonatal intrahepatic cholestasis caused by Citrin defiency (NICCD). Methods Twenty-nine NICCD infants were diagnosed by blood tandem mass spectrometry (MS-MS)analysis and/or SLC25A13 mutation analysis from July 2012 to February 2015 in Children's Hospital of Chongqing Medical University.Clinical data of 29 cases were analyzed retrospectively which included manifestations, laboratory features and prognosis.The general situation, feeding, liver function, growth were followed up. Results Twenty-nine infants suffering from NICCD presented jaundice in an early time, and some clinical manifestations were investigated such as hepatomegaly (20/29 cases), splenomegaly (3/29 cases), anemia (14/29 cases), and failure to thrive (9/29 cases). Laboratory data suggested that all of 29 patients had increased conjugated bilirubin, total bile acid, γ-glutamyl transferase and alkaline phosphatase. Some patients also showed abnormal coagulation function (20/22 cases), dyslipidemia (9/20 cases), increased blood lactic acid (22/26 cases) and alpha-fetoprotein (14/14 cases), decreased albumin(24/29 cases), blood glucose(17/22 cases) and ceruloplasmin(4/4 cases). The pathological analysis of one patient's liver indicated the edema and degeneration of liver cells, intrahepatic cholestasis and a small amount of fibrous tissue hyperplasia in portal area.MS-MS analysis of blood samples revealed distinctive increase in methionine, tyrosine, threonine, citrulline, arginine and free carnitine, long-chain acyl-carnitine in most patients.Gas chromatography-mass spectrometer (GC-MS) analysis of urine samples mainly showed elevated 4-hydroxyphenyllactic acid and 4-hydroxyphenylpyruvic acid.Prognosis showed that most of the NICCD patients (8/29 cases) could recover in one-year old with a lactose-free, medium chain triglyceride-enriched formula, and one patient died of liver cirrhosis.Three patients at over one-year old had the preference of a high protein and low carbohydrate diet. Conclusions Infants might be considered to have NICCD if they have jaundice in an early time, with the clinical characteristics of hepatomegaly, splenomegaly, abnormal coagulation function, anemia, failure to thrive, dyslipidemia, decresed albumin and blood glucose, increased blood lactic acid and alpha-fetoprotein.After that further tests of MS-MS, GC-MS and gene analysis of this disease are needed to confirm diagnosis. Key words: Citrin deficiency; Intrahepatic cholestasis; Clinical manifestation; Laboratory finding; Prognosis

Development of a tree shrew metabolic syndrome model and use of umbilical cord mesenchymal stem cell transplantation for treatment.

The aim of this study was to establish a tree shrew metabolic syndrome model and demonstrate the utility of MSCs in treating metabolic syndrome. We used tree shrew umbilical cord mesenchymal stem cell (TS-UC-MSC) transplantation for the treatment of metabolic syndrome to demonstrate the clinical application of these stem cells and to provide a theoretical basis and reference methods for this treatment. Tree shrew metabolic syndrome model showed significant insulin resistance, high blood sugar, lipid metabolism disorders, and hypertension, consistent with the diagnostic criteria. TS-UC-MSC transplantation at 16weeks significantly reduced blood sugar and lipid levels, improved insulin resistance and the regulation of insulin secretion, and reduced the expression levels of the pro-inflammatory cytokines IL-1 and IL-6 (P<0.05). The transplanted TS-UC-MSCs targeted the liver, kidney and pancreas; reduced liver cell degeneration, necrosis, and inflammatory exudation; mitigated bleeding congestion and inflammatory cell infiltration in the kidney; and reduced islet cell degeneration and necrosis. We successfully developed a tree shrew metabolic syndrome model and showed that MSC migrate in diseased organs and can attenuate metabolic syndrome severity in a tree shrew model.

Hepatoprotective potentials of Picralima nitida against in vivo carbon tetrachloride-mediated hepatotoxicity

This research aimed at investigating the in vivo Carbon tetrachloride (CCl4)-mediated hepatotoxicity of methanolic seed extract of Picralima nitida (P. nitida) using Wistar rats. Twenty five (25) rats randomly selected into five groups of five animals were used in this research. Group 1 was administered Normal saline (Negative control); Group II was administered 1 ml of Carbon tetrachloride only (Positive control/ Reference drug); Group III, IV and V got 10 ml P. nitida extract + 1ml Carbon tetrachloride; 100 ml P. nitida extract + 1ml Carbon tetrachloride and 1000 ml P. nitida extract + 1ml Carbon tetrachloride respectively. Results show that treatment with P. nitida extract had no adverse effect on the body weight of Wistar rats. Biochemical analysis show increase in CAT and GSH which are good antioxidant agents. Photomicrographs show moderate amelioration from steatosis caused by Carbon tetrachloride in the treatment groups. Further study is recommended to verify if P. nitida seed extract can completely ameliorate and possibly reverse fat degeneration of liver cells induced by Carbon tetrachloride.

Stemness-related transcriptional factors and homing gene expression profiles in hepatic differentiation and cancer.

Stem cell transcriptional signature activation is an essential event in the development of cancer. This study aimed to investigate the differential expression profile of three pluripotency-associated genes (OCT4, NANOG, and SOX2), G-protein-coupled chemokine receptor 4 (CXCR4) and the ligand (CXCL2), and alpha feto-protein (AFP) in hepatogenic differentiated stem cells and in sera of hepatitis C virus (HCV) and HCV-induced hepatocellular carcinoma (HCC) patients. Mesenchymal stem cells derived from umbilical cord blood were differentiated using hepatogenic differentiation media. Serum specimens were collected from 96 patients (32 cirrhotic HCV, 32 early HCC, and 32 late HCC) and 96 controls. Real-time quantitative reverse transcription polymerase chain reaction was performed for relative quantification of the 6 target genes using LIVAC method. In silico network analysis was also executed to explore the pluripotency and tumorigenic regulatory circuits in liver cancer. The expression levels of all genes declined gradually during the stages of stem cell differentiation. On univariate and multivariate analyses, NANOG, CXCR4 and AFP were significantly up-regulated in HCC patients with late clinical stage. In contrast, SOX2 and CXCL2 were markedly over-expressed in cirrhotic patients and could be used for clear demarcation between cirrhotic and HCC patients in our cases. In conclusion, our data highlight the potential role of SOX2 stem cell marker and CXCL2 chemokine in liver cell degeneration and fibrogenesis in HCV-induced hepatic cirrhosis in our sample of the Egyptian population. In addition, the significant association of NANOG and CXCR4 high-expression with late HCC, could contribute to the acquisition of stem cell-like properties in hepatic cancer and dissemination in late stages, respectively. Taken together, our results could have a potential application in HCC prognosis and treatment.

Effect of silver nanoparticles in the liver of female quail (Coturnix coturnix )

This study aimed to identify the alterations of liver in the quail (Coturnix coturnix) exposed by nanosilver particles.45 quail (females) were collected from agriculture research center in Abu-Ghraib, divided into (6) groups including: T1(12 quails were exposed to 4ppm), T2 (12 quails were exposed to 8ppm) and T3 (12 quails were exposed to 12ppm) of silver nanoparticles solution for 60 days. As well as three groups for control (3 females for each). Birds were dissected to isolate livers for histological preperations after fixation with Bouin's fluid, Routine stains Hematoxyline and eosin were used. Histological study showed that the structure of liver in a control groups consist of hepatocytes arranged radially cords around the central vein, Polygonal in shape with central nucleus. Sinusoid found between hepatocytes cords. The histological alterations in liver tissue included congestion of central vein, Fibrinous exudates , Infilteation of inflammatory cells, Thickness of capsule , Loss radial arrangement of hepatocytes , Incidence of fatty degeneration, Hydropic and Hyaline degeneration of hepatocytes , Appearing of councilman bodies, Pyknotic necrosis and few dilated of sinusoids in liver of group exposed to 4ppm. While the alterations in the liver with group 8ppm included occurance of precipitation of proteins near the vessels which known Amylloid , central vein dilation, An increase thickness of wall blood vessels, In addition an incidence of hemorrhage and hyaline degeneration of liver cells. Liver in group 12ppm suffer from incidence of fatty changes, Hydropic degeneration, Necrosis, Increase numbers of Concilman bodies, An incidence of giant cells, Atrophy of liver cells, Appearance of caceous necrosis and increase dilation of sinusoids and congestion.

Effect of silver nanoparticles in the liver of female quail (Coturnix coturnix )

This study aimed to identify the alterations of liver in the quail (Coturnix coturnix) exposed by nanosilver particles.45 quail (females) were collected from agriculture research center in Abu-Ghraib, divided into (6) groups including: T1(12 quails were exposed to 4ppm), T2 (12 quails were exposed to 8ppm) and T3 (12 quails were exposed to 12ppm) of silver nanoparticles solution for 60 days. As well as three groups for control (3 females for each). Birds were dissected to isolate livers for histological preperations after fixation with Bouin's fluid, Routine stains Hematoxyline and eosin were used. Histological study showed that the structure of liver in a control groups consist of hepatocytes arranged radially cords around the central vein, Polygonal in shape with central nucleus. Sinusoid found between hepatocytes cords. The histological alterations in liver tissue included congestion of central vein, Fibrinous exudates , Infilteation of inflammatory cells, Thickness of capsule , Loss radial arrangement of hepatocytes , Incidence of fatty degeneration, Hydropic and Hyaline degeneration of hepatocytes , Appearing of councilman bodies, Pyknotic necrosis and few dilated of sinusoids in liver of group exposed to 4ppm. While the alterations in the liver with group 8ppm included occurance of precipitation of proteins near the vessels which known Amylloid , central vein dilation, An increase thickness of wall blood vessels, In addition an incidence of hemorrhage and hyaline degeneration of liver cells. Liver in group 12ppm suffer from incidence of fatty changes, Hydropic degeneration, Necrosis, Increase numbers of Concilman bodies, An incidence of giant cells, Atrophy of liver cells, Appearance of caceous necrosis and increase dilation of sinusoids and congestion.

Experimental study on effect of model on hepatic fibrosis with Aralia chinesis

Hepatic fibrosis models were induced by CCl4 in rats. To explore vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGFβ1) mRNA expression and bcl-2, Bax protein expression levels of intervention and explore the mechanism of the Aralia chinesis anti-hepatic fibrosis. Sixty male Sprague-Dawlley (SD) rats were randomly divided into six groups: nomal group, model group, high-dose (10 mL x kg(-1)), medium-dose (7.5 mL x kg(-1)), low-dose (5.0 mL x kg(-1)) of A. chinesis treated group and colchicine treated group. The change of liver histopathology was observed by HE and Masson staining. The mRNA of VEGF, TGF-β1 were detected by RT-PCR. The protein of Bcl-2 and Bax were detected by Western blot. In the model group liver cell obvious degeneration, necrosis, a large number of collagen fibers of the cable hyperplasia, part visible pseudolobule formation. A. chinesis large, medium, low-dose group and colchicine group liver cell degeneration and necrosis reduced A. chinesis small, medium, and high-dose group was gradually reduced trend and A. chinesis large, middle dose group degree of reduction is particularly significant. Compared with model group, A. chinesis of large, medium and small dose group and colchicine group VEGF mRNA expression, A. chinesis of large, medium-dose group TGF-β1 mRNA expression reduce (P < 0.05); compared with colchicine group, A. chinesis of large, middle dose group of VEGF mRNA expression decreased (P < 0.05); A. chinesis of large, middle dose group of TGF-β1 mRNA expression decreased (P < 0.01), and compared with colchicine group, large dose group of of TGF-β1 mRNA expression decreased (P < 0.05). Compared with model group, A. chinesis of large, medium and small dose group and colchicine group Bcl-2 protein expression reduce (all is P < 0.05). But A. chinesis of large, medium and small dose group and colchicine group of Bax protein expression were increased (P < 0.05). A. chinesis regulation of VEGF, TGF-β1 may prevent the activation of hepatic stellate cells, liver tissue by up regulating the anti-apoptotic protein Bax and down pro-apoptotic protein Bcl-2 expression, thereby to improve the degree of liver fibrosis.

Pseudocholinesterase as a prognostic marker for liver disorder

Background: Liver is the main source of pseudo cholinesterase. It is a non-specific cholinesterase found in the blood plasma and may be reduced in patients with advanced liver diseases. Measurement of serum pseudo cholinesterase activity serves as a sensitive indicator of synthetic capacity of the liver and can be used as a prognostic marker for carcinoma.Objective: To study pseudo cholinesterase activities in liver diseases.Method: A prospective study was conducted at College of Medical Sciences Teaching Hospital (CMS-TH), from May 2011 to May 2013 with 25 controls and 25 diagnosed cases each of carcinoma of liver, cirrhosis of liver, infective hepatitis and obstructive jaundice among both sexes of same age group attending medical outpatient and inpatient departments. Serum pseudo cholinesterase and other liver function tests were performed with semi-auto analyzer and Roche Hitachi 902 respectively.Results: Pseudo cholinesterase level was markedly decreased in carcinoma of liver (mean ± SD = 1369.48 ± 276.64 IU/L) followed by cirrhosis of liver (mean ± SD = 1735.16 ± 433.82 IU/L), infective hepatitis (mean ± SD = 3800.69 ± 764.17 IU/L), obstructive jaundice (mean ± SD = 5539 ± 791.05 IU/L) when compared with controls (mean ± SD = 6865.12 ± 928.41 IU/L). The difference in the means was statistically significant (p &lt;0.001).Conclusion: There was significant decrease in pseudo holing esterase level in carcinoma of liver followed by cirrhosis of liver while less so in infective hepatitis. In obstructive jaundice the enzyme level was found to be decreased but higher than other liver diseases. The results indicated that with more severe liver cell destruction or cell degeneration, there was corresponding significant decrease in the level of pseudo cholinesterase, which could be used as diagnostic marker of liver disease.Journal of Kathmandu Medical College Vol. 3, No. 4, Issue 10, Oct.-Dec., 2014Page: 131-135

Clinical Outcome of Autologous Hematopoietic Stem Cell Infusion via Hepatic Artery or Portal Vein in Patients with End-stage Liver Diseases

To investigate the efficacy of hematopoietic stem cell (HSC) transplantation via the hepatic artery vs. the portal vein for end-stage liver disease (ESLD). Patients with hepatic decompensation were prospectively recruited from September 2010 to September 2012 to receive HSC transplantation via the hepatic artery or the portal vein. Liver function was examined at 3, 6, and 12 months after transplantation. Liver biopsy Results were analyzed using the Knodell score. Eighty patients (58 males and 22 females) were enrolled in the study. The Child-Pugh score was grade B in 69 cases, and grade C in the remaining 11 cases. HSC transplantation was performed via the portal vein in 36 patients and via the hepatic artery in 44 patients. ALT levels decreased while serum albumin levels increased significantly in both groups at 6 and 12 months after HSC transplantation (P<0.05 compared with pre-transplantation levels). Total bilirubin levels decreased significantly in both groups at 3, 6, and 12 months after HSC transplantation (P<0.05 compared with pre-transplantation levels). Additionally, prothrombin time decreased in both groups at 12 months after HSC transplantation (P<0.05 compared with pre-transplantation level). There were no significant differences in ALT, total bilirubin and prothrombin time between the two groups either before or after transplantation. Moreover, Knodell score decreased significantly at 6 and 12 months. Histological examination showed that liver cell edema, degeneration, necrosis, and inflammation were significantly relieved at 3, 6, and 12 months after transplantation. The incidence of portal vein thrombosis, upper gastrointestinal bleeding, and hepatic encephalopathy were 1.25%, 3.75%, and 2.5% respectively. The one-year survival rate was 100%. Autologous HSC transplantation improves liver function and histology in ESLD patients. The administration route of HSC has no significant impact on the efficacy of transplantation.

Comprehensive review of 18 cases with Abernethy malformation in China from 2001 to 2012

Objective To acquire more knowledge about Abernethy malformation. Methods Eighteen cases with Abernethy malformation published previously in China from 2001 to 2012 were reviewed.The clinical, radiological and pathological manifestations and treatment were summarized. Results Of 13 cases with type Ⅰ Abernethy malformation (including 6 type Ⅰ a and 7 type Ⅰ b, 5 male and 8 female ), 11 cases occurred by the age of 18 years.Their clinical manifestations included hematochezia in 4, hematemesis in 4, liver dysfunction in 5, liver cirrhosis in 2, hepatic encephalopathy in 2, hepatic nodule in 4, splenomegaly in 5, hypersplenism in 4, portal hypertension in 3 and other associated malformations in 3.Of 5 cases with typeⅡAbernethy malformation, 2 cases occurred by the age of 18 years.Their clinical manifestations included liver dysfunction in 4, hematochezia in 1, liver cirrhosis in 1, hepatic encephalopathy in 1, hepatic nodule with focal nodular hyperplasia in 1.All 18 patients underwent imaging evaluation, multi-slice computed tomography(CT) angiography (MSCTA) in 16, including vascular ultrasound in 15, digital subtraction angio-graphy (DSA) in 7, magnetic resonance angiography (MRA) in 1 and magnetic resonance imaging (MRI) in 1.The sites of drainage for portal vein system in 15 cases were documented, including the inferior vena cava (2/15 cases), internal iliac vein (5/15 cases), left renal vein (3/15 cases), azygos vein (2/15 cases), right atrium (2/15 cases) and pelvic venous plexus (1/15 case). And there was no record of specific draining site in other 3 cases.Ballooning dege-neration of liver cells, liver cells nodular hyperplasia and fatty degeneration were detected in 2 cases of type Ⅰ Abernethy malformation.And liver focal nodular hyperplasia was demonstrated in 1 case of typeⅡAbernethy malformation.Four cases with hematochezia were misdiagnosed as ulcerative colitis, hemorrhoids or purpura.Two cases with clitoral hypertrophy were misdiagnosed as genital malformations.Due to crying, one 5-month-old baby was misdiagnosed as sepsis.Of these 18 cases of Abernethy malformation, most of the cases received conservative treatment.Surgical techniques such as splenectomy, surgical ligation of the veins of sigmoid and interventional embolization to occlude the shunt were used to treat splenomegaly, hematochezia, hematemesis or hepatic encephalopathy. Conclusions Abernethy malformation mainly occurs in children.Clinical presentation is nonspecific.Liver dysfunction, hepatic nodule, hematochezia, hematemesis, plenomegaly and hypersplenism are common manifestations.Compared with overseas reports, hepatic nodule, hepatic encephalopathy and concomitant abnormalities are rare, while hematochezia and hematemesis are more common.The diagnosis is made primarily according to imaging changes, and MSCTA is a useful tool to make a diagnosis.Indivi-dualized treatment of Abernethy malformation is determined by the type of deformity and the conditions of the patient. Key words: Abernethy malformation; Absence of portal vein; Portocaval shunt

Model building-up and observation on the mouse carried chronic hepatitis B and nonalcoholic fatty liver disease

Establish the model of mouse with chronic hepatitis B virus (HBV) and nonalcoholic fatty liver disease (NAFLD). Take 100 HBV transgenic, BALB/c mice of 4 weeks old, with each gender half. Then pick out 70 mice in one group to feed high-fat feed and the rest to feed normal feed. At the end of week 16, random kill 10 mice of high-fat, then liver tissue and serological detection target identification model is established in this paper. After that, divide the mice into model group and comparison group with 30 mice in each group. Feed model group with high-fat feed, comparison group with normal feed and normal group with normal feed till week 72 (including previous 16 weeks). Kill 10 mice of each group at the end of week 24, 48 and 72 respectively, fully automatic biochemical instrument detection of serum ALT, AST, TC, TG, FBG, fluorescence quantitative PCR method to detect HBV-DNA, chemiluminescence detection of HBsAg, liver biopsy after HE staining to evaluate histology change, observe mice model of dynamic evolution. (1) Feed high fat feed after 16 weeks, mice's weight, serum ALT, AST, TC, TG, FBG and blood biochemical indicators increased, HBV-DNA positive, liver HE staining obviously big blister fatty degeneration of liver cells and within the lobule lymphocytes infiltration, NAFLD activity score (NAS) getting close to NASH, the model of chronic HBV carries with NAFLD mouse built successfully. (2) The TC and TG values of model group in each period were higher than that of comparison group and normal group. (3) In week 24 and 72, HBV-DNA values of each group are obvious different from the other two groups and the difference can be applied to statistical significance (P < 0.05). (4) In week 48 and 72, NAS of each group are obvious different from the other two groups and the difference can be applied to statistical significance (P < 0.05). (1) Chronic HBV carries with NAFLD mice model can be established by HBV transgenic mice fed by high fat feed. (2) NAFLD accelerates the liver disease of the mice carrying HBV to some extent.