Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An eleven year old boy was referred because of sudden loss of consciousness, muscular weakness, poor general health, severe hypoglycemia with seizures and hepatomegaly. Response to oral glucose and galactose increased blood lactic acid and glucose at different times. Fasting values of blood lactic was normal, but glucose was found at 33 mg/dl. Similar test made up two hours after feeding revealed hyperlactatemia (35-50 mg/dL) and hyperglycemia (129 mg/dL). Glucagon did not result in a rise of glucose at fasting or feeding. Hepatic glycogen content was found 15 gm/100 mg of tissue. The enzyme activities revealed a deficiency of the liver debranching enzyme while leukocytes had normal enzyme activity. Hepatic biopsy showed liver fibrosis. The present case had the clinical characteristics of severe form of glycogen storage disease. A low carbohydrate and high protein diet was indicated in order to increase the gluconeogenic precursors. Although debranching enzyme deficiency is almost always benign a high carbohydrate diet induced a more severe expression of the disease.
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PMID:Diet therapy in severe clinical expression of debrancher deficiency. 184 14

The use of the Tsukamoto-French rat model of alcoholic liver disease facilitated pathological, physiological, biochemical and cell biological experiments that examined the validity of some of the existing hypotheses for pathogenesis of alcoholic liver necrosis and fibrosis. Results obtained to date strongly support the contribution of centrilobular hypoxia as a pathogenetic mechanism of alcoholic liver necrosis. The enhanced hepatic lipid peroxidation was not evident at the early stage of ethanol-induced liver necrosis but could be demonstrated at the late stage when the liver damage progressed to liver fibrosis. This suggests that the lipid peroxidation may not be an important mechanism of alcoholic liver necrosis but may be an initiation factor for liver fibrogenesis as recently proposed by others (88). The high-fat diet appears to have promoting effects on both induction of alcoholic liver necrosis and stimulation of liver fibrogenesis. The former may be related to the induction of MEOS by the high-fat diet and consequent centrilobular hypoxia caused by inadequately compensated hepatic overuse of oxygen. The latter can be mediated through sensitization of Ito cells by a high-fat diet. We propose that Kupffer cell-derived TGF beta is, at least in part, responsible for some of phenotypical changes of Ito cells associated with their activation. Our model provides maximal experimental control and induces the discrete stages of alcoholic liver injury that can be reproduced with its pathological evolution telescoped into a short time. Because of these features, replication of the experimental conditions in different laboratories is possible so that results can be validly compared through precise standardization of the experimental protocols. This model requires some training in implantation and maintenance of the gastric catheter. However, the training can be easily attained by anyone who has experience in animal surgery. Another requirement is the initial fund to acquire infusion devices and metabolism cages. Once this equipment is purchased, however, the maintenance cost is low. Even if the initial expenses are included, the cost per animal is relatively inexpensive when compared with the cost involved in the use of larger animals such as baboons or pigs. Since administration of diet and ethanol (or isocaloric glucose solution) is precisely controlled by infusion pumps, this system makes unnecessary the measurement of diet consumption that has to be done daily for each animal with other methods.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insights into the pathogenesis of alcoholic liver necrosis and fibrosis: status report. 220 58

Carbohydrate metabolism in 9 infants with biliary atresia (BA) was investigated preoperatively and during the early postoperative period when these infants were on parenteral nutrition for 7 days. Findings were compared with data on infants without liver dysfunction. Changes of plasma glucose, immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) in the biliary atresia group with moderate liver fibrosis were the same as those in the control group. However, in one patient with marked liver fibrosis, the molar IRI/CPR ratio was significantly low, thereby suggesting an increased hepatic insulin extraction. This change, however, was transient and the molar IRI/CPR ratio gradually returned to the level of other BA patients and the control groups after the 1st postoperative day. This study shows that in infants with BA, the glucose intolerance seen in adults with obstructive jaundice is absent and the parenteral nutrition can be performed without severe changes of carbohydrate metabolism.
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PMID:Carbohydrate metabolism in infants with biliary atresia. 355 81

Sake or bourbon (8g ethanol/kg body weight) was intragastrically administered to rats for 12 days. An equal dose of ethanol in water or an isocaloric glucose solution was administered to control groups. Food was withheld, but water freely provided. Neither mortality nor liver and body weights were different between the alcohol-treated groups. Glutamic oxaloacetic transaminase and glutamic pyruvic transaminase were more elevated in the sake group than in the other groups. Additionally, liver fibrosis was more pronounced, and vacuole formation or steatosis was less in this group. These results suggest that sake is more fibrogenic. Some components other than ethanol, such as long-alkyl chain alcohols, may have been responsible for the differential histopathology.
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PMID:Effects of sake and bourbon on liver histopathology and function in rats. 652 45

The therapeutic effect of most immunosuppressive agents is unspecific and therefore often limited by an increased risk of infection by viral, bacterial or fungal organisms as well as by an increased incidence of malignant neoplasms. This short review includes the most commonly used immunosuppressants such as corticosteroids, azathioprine, methotrexate, cyclophosphamide and cyclosporine. The most common risks of long-term corticosteroid treatment are Cushing-like changes, decreased glucose tolerance and the usually benign steroid diabetes. Also clinically important is osteoporosis, since it can be prevented by physical training, calcium supplementation and treatment with vitamin D if necessary. Although there is still no proof of a significantly increased risk of peptic ulcer during steroid therapy, patients may develop gastrointestinal hemorrhage and even perforation without producing pain while being treated with corticosteroids. Mineralocorticoid effects, such as salt and water retention, are seen only with hydrocortisone and prednisone, whereas with synthetic steroids such as dexamethasone, sodium retention is absent despite their strong antiphlogistic activity. The most important side effect of the cytotoxic agents azathioprine, methotrexate and cyclophosphamide is marrow suppression. Due to the high turnover of neutrophils, patients most frequently suffer neutropenia rather than thrombocytopenia or anemia. Neutropenia, as well as impaired humoral and cellular immune mechanisms, are responsible for increased susceptibility to bacterial, viral or parasitic diseases during immunosuppressive therapy. Hepatotoxicity has been reported among patients receiving azathioprine (cholestatic hepatitis) and methotrexate (elevated AST levels and, rarely, liver fibrosis or cirrhosis). Cyclophosphamide causes hemorrhagic cystitis in a substantial proportion of patients, as well as an increased incidence of urothelial neoplasms. Both these side effects may be prevented by Mesna. The most important side effects of cyclosporine are acute and chronic nephrotoxicity usually associated with significantly elevated plasma levels of the drug. It must be borne in mind that severe nephrotoxicity may occur in patients receiving cyclosporine and ketoconazole together, since the latter may inappropriately increase the plasma cyclosporine level.
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PMID:[Immunosuppression--a tightrope walk between iatrogenic harm and therapy]. 892 65

A case of septicemia due to Aeromonas hydrophila (A. hydrophila) in a 54-year-old male suffering from progressive severe jaundice and fatigue is reported. The patient developed multiple organ failure despite aggressive therapy including plasma exchange and glucose-insulin therapy. Upon admission to our hospital, therapy was started with ampicillin (ABPC) 4 g/day, gentamicin (GM) 120 mg/day, hemodialysis, continuous hemofiltration, catecholamines and a respirator, but he expired on the 2nd hospital day. Blood culture and histology revealed A. hydrophila. Postmortem examination showed alcoholic liver fibrosis which was most likely liver cirrhosis. In the literature, patients with septicemia due to Aeromonas had underlying hepatic cirrhosis more often than did those with septicemia due to other gram-negative bacilli. Therefore, it is important-to consider the possibility of liver cirrhosis in patients with A. hydrophila septicemia.
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PMID:[A case of severe acute hepatorenal failure due to Aeromoas hydrophila septicemia]. 895 74

This study assesses the long-term results of jejunoileal bypass (JIB) in 43 prospectively followed patients whose surgical bypass remained intact. Follow-up was 12.6+/-0.25 years from JIB. Weight loss and improved lipid levels, glucose tolerance, cardiac function, and pulmonary function were maintained. Adverse effects such as hypokalemia, cholelithiasis, and B12 or folate deficiency decreased over time. The incidence of diarrhea remained constant (63% vs 64% at five years), while the occurrence of hypomagnesemia increased (67% vs 43% at five years, P < 0.05). Nephrolithiasis occurred in 33% of patients. Hepatic fibrosis developed in 38% of patients and was progressive. Overall, after more than 10 years, 35% of patients appeared to benefit from JIB as defined by alleviation of preoperative symptoms and the development of only mild complications (vs 47% at five years). On the other hand, irreversible complications appeared to outweigh any benefit derived from the JIB in 19% (vs no patients at five years; P < 0.01). In summary, patients with JIB remain at risk for complications, particularly hepatic fibrosis, even into the late postoperative period.
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PMID:Long-term consequences after jejunoileal bypass for morbid obesity. 982 41

Blood galactose clearance after an intravenous galactose load has been widely used for years as an index of liver function. We developed a noninvasive [13C]galactose breath test, which explores galactose oxidative metabolism; this test is well correlated with liver fibrosis in patients with chronic viral hepatitis. The goal of this study was to evaluate the influence of nonhepatic factors such as diabetes and ethanol on whole-body galactose clearance (measured as the serum galactose elimination capacity test) and oxidative metabolism (measured as the [13C]galactose-induced breath 13CO2 production) in rats. Acute ethanol administration induced a significant decrease of galactose clearance and 13CO2 production. There was a significant correlation between the amount of ethanol given and the inhibition of galactose metabolism (R2 = 0.72, p < 0.0001). In streptozotocin-induced diabetic rats, the [13C]galactose-induced breath 13CO2 production was significantly reduced (p < 0.0001) and normalized by insulin treatment. However, diabetes did not decrease whole-body galactose clearance, indicating an isotopic dilution of [13C]glucose produced from [13C]galactose metabolism into the enlarged glucose pool. These results must be taken into account when using the [13C]galactose breath test as a quantitative liver function test.
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PMID:Effects of ethanol and diabetes on galactose oxidative metabolism and elimination in rats. 1053 91

Obesity is associated with a number of metabolic and haemodynamic risk factors for cardiovascular disease and type 2 diabetes mellitus. This risk depends on a complex of metabolic and haemodynamic consequences of (visceral) fat accumulation, which probably results from the continuous delivery of fatty acids to the liver via the portal vein. Hypertriglyceridaemia, hyperinsulinaemia, hypertension, insulin resistance and increased hepatic glucose production are all independent risk factors for atherosclerosis. Their combination increases the risk of cardiovascular disease considerably. Triglyceride storage in hepatocytes is another consequence of increased fatty acid supply to the liver. Until recently, hepatic steatosis was considered a harmless condition secondary to obesity or alcoholism. However, it may lead to non-alcoholic hepatic steatosis, which predisposes to liver fibrosis and even cirrhosis.
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PMID:[Abdominal obesity: metabolic complications and consequences for the liver]. 1160 19

Nonalcoholic steatohepatitis (NASH) may progress to liver fibrosis and cirrhosis. Mechanisms directly involved in the development of fibrosis have been poorly investigated. Because connective tissue growth factor (CTGF) is an intermediate key molecule involved in the pathogenesis of fibrosing chronic liver diseases and is potentially induced by hyperglycemia, the aims of this study were to (1) study the expression of CTGF in vivo both in human liver biopsy specimens of patients with NASH and in an experimental model of obesity and type II diabetes (Zucker rats); and (2) analyze the effects of hyperglycemia and insulin in vitro on hepatic stellate cells. In vivo, CTGF overexpression was observed in the liver tissue of all of the 16 patients with NASH. CTGF immunostaining was mild in 7 cases (44%) and moderate or strong in 9 cases (56%). Staining was mainly detected in the liver extracellular matrix in parallel with the amount of liver fibrosis. Liver from fa/fa rats also showed CTGF overexpression by comparison with Fa/fa rats both at the messenger RNA (mRNA) level (3-fold increase) and protein level. In vitro, both CTGF mRNA and protein were significantly increased when hepatic stellate cells were incubated with either glucose or insulin. A slight increase in type I procollagen mRNA level was also observed in hepatic stellate cells incubated with glucose. In conclusion, this study suggests that hyperglycemia and insulin are key-factors in the progression of fibrosis in patients with NASH through the up-regulation of CTGF.
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PMID:High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. 1158 70


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