Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two patients in whom accidental hepatic artery occlusion (HAO) occurred after hepatic resection (Hx) were reported. A 59-year-old female who underwent Hx for hepatocellular carcinoma with underlying liver cirrhosis developed HAO on postoperative day (POD) 14 and died of hepatic failure on POD 23. The autopsy findings showed multiple necrosis in the remnant liver and an extraluminal hematoma of the hepatic artery, suggesting an injury caused by Pringle's maneuver. The second case was a 53-year-old male who underwent Hx for cholangiocarcinoma without any underlying liver disease. He developed HAO on POD 6, and radiological studies indicated a pseudoaneurysma formation and severe stenosis of the hepatic artery. It was speculated that the cause of the HAO was intraluminal injury of the hepatic artery during an angiographic study conducted prior to Hx. Partial arterialization of the portal vein was performed, following which his liver function test results improved. In both cases, measuring the serum hepatocyte growth factor level and the hepatic vein oxygen saturation proved useful, not only for determining the degree of liver injury, but also for predicting the outcome after treatments for HAO. Furthermore, the partial arterialization of the portal vein for HAO after Hx may rescue the normal remnant liver.
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PMID:Treatment for accidental occlusion of the hepatic artery after hepatic resection: report of two cases. 1019 41

Fumonisin B1 (FB1) is a carcinogenic mycotoxin produced by the fungus Fusarium moniliforme in corn. Feeding of FB1 to rats causes acute liver injury, chronic liver injury progressing to cirrhosis, and sometimes terminates in hepatocellular carcinoma or cholangiocarcinoma. This study describes the histolopathology and changes in gene expression in the rat liver during short-term feeding of FB1. Male Fischer rats were fed either FB1 250 mg/kg or control diet, and were killed weekly for 5 weeks. FB1 caused a predominantly zone 3 'toxic' liver injury, with hepatocyte death due to necrosis and apoptosis. Hepatocyte injury and death were mirrored by hepatic stellate cell proliferation and marked fibrosis, with progressive disturbance of architecture and formation of regenerative nodules. Despite ongoing hepatocyte mitotic activity, oval cell proliferation was noted from week 2, glutathione S-transferase pi-positive hepatic foci and nodules developed and, at later time points, oval cells were noted inside some of the 'atypical' nodules. Northern blot (mRNA) analysis of liver specimens from weeks 3 to 5 showed a progressive increase in gene expression for alpha-fetoprotein, hepatocyte growth factor, transforming growth factor alpha (TGF-alpha) and especially TGF-beta1 and c-myc. Immunostaining with LC(1-30) antibody demonstrated a progressive increase in expression of mature TGF-beta1 protein by hepatocytes over the 5 week feeding period. The overexpression of TGF-beta1 may be causally related to the prominent apoptosis and fibrosis seen with FB1-induced liver injury. Increased expression of c-myc may be involved in the cancer promoting effects of FB1.
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PMID:Histopathology and gene expression changes in rat liver during feeding of fumonisin B1, a carcinogenic mycotoxin produced by Fusarium moniliforme. 1033 99

We previously reported that in vitro hypoxic condition enhanced VEGF level and its receptor expression in hepatic cancer cell line, HepG2. Transcatheter hepatic arterial embolization (TAE) therapy is one of the vasculo-occlusive and hypoxic challenges to hepatocellular carcinoma (HCC). Therefore, we examined the level of VEGF in sera of patients with HCC who underwent TAE during the course of the treatment. Thirty-eight patients with HCC and hepatitis C virus-positive cirrhosis were studied. Peripheral blood samples were taken before and 1, 3 and 7 days after TAE with informed consent. The serum levels of VEGF as well as hepatocyte growth factor (HGF), another hepatic remodeling factor, were measured. The molar ratio (BTR) of serum branched chain amino acid (BCAA) to tyrosine (Tyr), the serum levels of AST, ALT and LDH were also examined. Although the level of AST, ALT and LDH reached the peak value within 1 day after TAE, VEGF level increased significantly 7 days later. On the other hand, there were no significant alterations in the levels of HGF and BTR during the course of TAE. Although the level of HGF was significantly correlated with the level of VEGF before TAE, this correlation was no more observed after TAE. These data collectively suggest that VEGF may be secreted in response to clinical hypoxic intervention, TAE, independent of HGF or altered amino acid metabolism. VEGF may play a role as a sensitive marker for tumor ischemia.
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PMID:Serum vascular endothelial growth factor in the course of transcatheter arterial embolization of hepatocellular carcinoma. 1033 62

Cirrhotic liver is considered to regenerate less actively than normal liver after hepatic resection. However, the mechanisms responsible for this impaired regeneration and the cross talk of implicated factors still remain unclear. In the present study, mRNA levels for cyclins, growth factors, and cytokines were quantitatively assessed by a RT-PCR method at different times after hepatectomy in order to determine the relationships between these factors and the impaired regenerative process observed in cirrhotic liver. In our model of CCl(4)-induced cirrhosis, mRNA levels for cyclins and thymidine kinase provide evidence for the impaired and delayed hepatic regeneration. Moreover, we observed a significant decrease in interleukin (IL)-6 and tumor necrosis factor-alpha mRNA and a significant increase for IL-1beta mRNA. No significant change of hepatocyte growth factor (HGF) mRNA level was detected, contrasting with the decrease both at mRNA and protein levels in the expression of the c-Met/HGF receptor. Therefore, the impaired regeneration of the cirrhotic liver is associated not only with a lowered level of signals that normally promote liver growth but also with a strong decrease in c-Met receptor despite a normal expression of its specific ligand.
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PMID:Changes in growth factor and cytokine mRNA levels after hepatectomy in rat with CCl(4)-induced cirrhosis. 1051 50

Liver cirrhosis is an inveterate disease accompanying fibrosis, hepatocyte damage, and liver dysfunction. In this study, the therapeutic effects of recombinant human hepatocyte growth factor (rhHGF) on liver cirrhosis were examined in rats administered thioacetamide (TAA). Repeated administration of TAA for 10 weeks to rats induced liver cirrhosis with collagen nodes and pseudo-lobe generation, a condition that was pathologically similar to that in humans. Administration of rhHGF after the formation of liver cirrhosis markedly decreased the incidence of pathological fibrosis and the degree of fibrosis as measured by a computed image analysis system. Continuous administration of rhHGF by infusion pump was more effective than bolus administration. Northern blotting analysis showed that rhHGF reduced mRNA levels of procollagen alpha2(I), alpha1(IV), and transforming growth factor-beta1 (TGF-beta1) that were stimulated in the TAA-treated liver. The labeling index of hepatocytes increased following administration of rhHGF in this model. These observations suggest that the pathological recession of liver fibrosis is the result of the reduction of TGF-beta1 and collagen synthesis and, in part, of the stimulation of mitosis of hepatocytes directly by rhHGF and indirectly by TGF-beta1 reduction in the cirrhotic liver. These results demonstrate the usefulness of rhHGF as a therapeutic agent in liver cirrhosis.
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PMID:The decrease in total collagen fibers in the liver by hepatocyte growth factor after formation of cirrhosis induced by thioacetamide. 1067 85

Liver cirrhosis is the irreversible end result of chronic liver disease and is characterized by fibrous scarring and hepatocellular regeneration. It is a major cause of morbidity and mortality worldwide and is induced by factors such as chronic hepatitis virus infection, drug abuse and alcohol abuse. The ideal strategy for the treatment of liver cirrhosis should include prevention of fibrogenesis, stimulation of hepatocyte mitosis and reorganization of the liver architecture. Hepatocyte growth factor (HGF) gene therapy has been investigated in a rat model of liver cirrhosis. In rats with lethal liver cirrhosis produced by dimethylnitrosamine, repeated transfection of the HGF gene into skeletal muscle induced a high plasma level of HGF and tyrosine phosphorylation of the c-Met/HGF receptor. Hepatocyte growth factor gene transduction inhibited fibrogenesis and hepatocyte apoptosis and also produced resolution of fibrosis in the cirrhotic liver. Hepatocyte growth factor gene therapy may have the potential to be useful for the treatment of patients with liver cirrhosis.
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PMID:Gene therapy for liver cirrhosis. 1075 18

Hepatocyte growth factor/scatter factor (HGF/SF) is one of the most important humoral mediators of liver regeneration. It is potentially related to molecular mechanisms of hepatocarcinogenesis via a paracrine system involving its cellular receptor, c-met. In this study, the expression patterns of HGF and c-met were evidenced by multiplex RT-PCR in different specimens of human hepatic tissues (n = 71). A significant increase of c-met mRNA expression was detected in hepatitis (P = 0.001), cirrhosis (P = 0.006), and hepatocellular carcinoma (HCC) tissue (P = 0.003) compared with normal parenchyma and steatosis. HGF mRNA expression was significantly higher only in hepatitis (P = 0.01). Over-expression of c-met mRNA and under-expression of HGF mRNA were detected in the HCCs compared with the corresponding peri-tumoral tissues. Neither HGF nor c-met expression was related to age, sex, tumor size, grading, presence of pseudocapsula, and proliferative activity of the malignant hepatocytes. A significant inverse correlation was found between c-met mRNA expression level and survival (in months) of patients (P = 0.007), as previously shown for urokinase-type plasminogen activator (u-PA) mRNA (P = 0.027). In addition, c-met mRNA expression was strictly associated with u-PA mRNA level in HCC samples (P = 0.001). These data show that a loss of balance concerning HGF, c-met, and u-PA mRNA expression occurs during hepatocarcinogenesis. Particularly, up-regulation of c-met and u-PA mRNA transcription appears to be coordinately regulated, and their levels of expression are inversely correlated with survival; they must therefore play an important role in the development and progression of human HCC and may also be relevant prognostic markers.
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PMID:u-PA and c-MET mRNA expression is co-ordinately enhanced while hepatocyte growth factor mRNA is down-regulated in human hepatocellular carcinoma. 1092 56

Liver cirrhosis represents a worldwide health problem and is a major cause of mortality. Cirrhosis is the result of extensive hepatocyte death and fibrosis induced by chronic alcohol abuse and hepatitis B and C viruses. Successful gene therapy approaches to this disease may require both reversal of fibrosis and stimulation of hepatocyte growth. Urokinase-type plasminogen activator (uPA) may serve this function, as it is an initiator of the matrix proteolysis cascade and induces hepatocyte growth factor expression. In a rat cirrhosis model, a single iv administration of a replication-deficient adenoviral vector encoding a nonsecreted form of human uPA resulted in high production of functional uPA protein in the liver. This led to induction of collagenase expression and reversal of fibrosis with concomitant hepatocyte and improved liver function. Thus, uPA gene therapy may be an effective strategy for treating cirrhosis in humans.
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PMID:Liver cirrhosis is reverted by urokinase-type plasminogen activator gene therapy. 1112 55

Liver cirrhosis is the irreversible end result of chronic liver disease, characterized by diffuse disorganization of the normal hepatic structure of regenerative nodules and fibrotic tissue. It is associated with prominent morbidity and mortality, and is induced by many factors. The ideal strategy for the treatment of liver cirrhosis should include prevention of fibrogenesis, stimulation of hepatocyte mitosis, and reorganization of the liver architecture. We have developed a novel gene therapy approach for rat liver cirrhosis by muscle-directed gene transfer of hepatocyte growth factor(HGF). HGF gene transduction inhibited fibrogenesis and hepatocyte apoptosis, and also produced resolution of fibrosis in the cirrhotic liver. Thus, HGF gene therapy may be potentially useful for the treatment of patients with liver cirrhosis, which is otherwise fatal and untreatable by conventional therapy.
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PMID:[Persectives on postgenome medicine: Gene therapy for liver cirrhosis]. 1119 47

We determined hepatocyte growth factor (HGF) levels in the serum and liver of patients with hepatitis C and assessed the relationship to histological findings of the liver and hepatitis C virus-related markers in the serum in patients with type C liver diseases. The subjects were 108 patients with chronic hepatitis C (CH), 70 patients with liver cirrhosis C (LC), 38 patients with hepatocellular carcinoma (HCC) and 20 patients with acute hepatitis (AH). As normal controls 20 subjects were studied. The serum HGF levels were measured using an enzyme-linked immunosorbent assay kit. Intrahepatic HGF was investigated by immunoperoxidase staining using monoclonal HGF antibody. The serum HGF level was highest in patients with AH. The serum HGF levels tended to be higher in patients with LC and HCC than those with CH. Further, the serum HGF level was related to the degree of intrahepatic inflammatory cell infiltration and fibrosis, and intrahepatic HGF was noted primarily in the cell membrane of mesenchymal cells in focal necrosis. The degree of intrahepatic HGF expression tended to be higher in patients with high serum HGF levels. In patients with HCC, however, HGF showed little localization in cancer cells, but was noted in infiltrating mesenchymal cells in both cancerous and noncancerous regions. In conclusion, the measurement of serum HGF levels may be useful for estimating the degree of intrahepatic inflammatory reaction and fibrosis. Although further study is necessary, the high serum level of HGF revealed high carcinogenic states in chronic hepatitis and liver cirrhosis type C.
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PMID:Detection of serum and intrahepatic human hepatocyte growth factor in patients with type C liver diseases. 1122 18


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