Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malnutrition is common among alcoholics because alcohol displaces protein-, vitamin-, and mineral-containing foods in the diet, and chronic alcohol consumption results in maldigestion and malabsorption of essential nutrients. In addition, alcohol exerts direct toxic effects on both the liver and gut, resulting in structural alterations in the intestine and the development of fatty liver, alcoholic hepatitis, and cirrhosis. Liver injury is preceded by an adaptive phase characterized by accelerated metabolism of drugs (including ethanol), and hyperlipemia, secondary to hypertrophy and hyperactivity of the smooth endoplasmic reticulum. Side effects include enhanced hepatotoxicity of CCI4 and possibly energy wastage. Alcoholics should not be led to beleive that correction or prevention of nutritional deficiency will prevent liver damage in the face of continued alcohol abuse.
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PMID:Alcohol and malnutrition in the pathogenesis of liver disease.. 117 54

Overgrowth of Gram-negative bacteria as a result of total parenteral nutrition (TPN) and bowel rest could be responsible for the release of a variety of hepatotoxic substances such as endotoxin or tumor necrosis factor (TNF) and the ensuing TPN-associated liver function derangements. Polymyxin B is an effective antimicrobial agent as well as a blocking agent for endotoxin (lipopolysaccharide) activity and TNF production. In the present study we compared the oral and intravenous effects of polymyxin in rats receiving TPN in an attempt to define these two possible mechanisms of action of polymyxin on TPN-associated hepatic steatosis. Both oral, as well as intravenous polymyxin B, significantly reduced total hepatic fat and triglyceride accumulation in TPN rats, more so in the intravenous group exhibiting close to control levels. Both polymyxin-treated groups exhibited significantly lower Gram-negative bacterial counts in the cecum, with the oral group exhibiting a lower count than the IV group. The spontaneous production of TNF by peritoneal macrophages was markedly increased in rats receiving TPN and very close to being undetected in both groups receiving TPN and polymyxin. We believe polymyxin B protects the liver during TPN by both its antimicrobial effect which prevents overgrowth of gut Gram-negative bacteria and the subsequent translocation of endotoxin, and by its specific antilipopolysaccharide activity which, in the present study, completely abolished hepatic steatosis and TNF production during TPN.
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PMID:Polymyxin B reduces total parenteral nutrition-associated hepatic steatosis by its antibacterial activity and by blocking deleterious effects of lipopolysaccharide. 149 9

This study was undertaken to determine whether refeeding through the native small intestine or through a small bowel transplant would reverse hepatic steatosis induced by total parenteral nutrition (TPN), and of what influence a coexisting short-gut syndrome is. Three short-gut syndromes of different severity were established in Lewis rats (short-gut I, mild; short-gut II, moderate; short-gut III, severe). TPN was administered for 10 days and the animals were refed for 20 days. A liver biopsy after the TPN period confirmed a mild to moderate fatty infiltration of the liver in all groups. After the refeeding period a second liver biopsy was obtained and no evidence of hepatic steatosis was observed in Groups 1, 2, 3, and 4 (normal Lewis rat, short-gut I, II, and III). The animals in group 5 (short-gut I) received a syngeneic small bowel transplant after discontinuation of TPN. After the refeeding period the liver biopsies showed no evidence of fatty infiltration. The intestinal graft also reversed the nutritional deficiencies which were observed in the animals with short-gut and showed normal body weight gain and nitrogen and fat uptake in comparison to the normal animals (Group 1). These data show that a small bowel graft is capable of reversing the deleterious sequelae of short-gut syndrome as well as the TPN-related hepatic steatosis.
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PMID:Hepatic steatosis due to total parenteral nutrition: the influence of short-gut syndrome, refeeding, and small bowel transplantation. 190 73

Plasma endotoxin concentration was measured in 85 patients with alcoholic liver disease (alcoholic cirrhosis (n = 64), alcoholic hepatitis without cirrhosis (n = 11), fatty liver (n = 10), and in patients with non-alcoholic cirrhosis (n = 15]. Endotoxin concentration was determined with an improved chromogenic substrate assay, using individual standard curves for each plasma sample. In patients with alcoholic cirrhosis the mean endotoxin concentration was significantly higher than in patients with non-alcoholic cirrhosis (p less than 0.05). In addition, distinctly higher endotoxin concentrations (greater than 20 pg/ml) were more frequently observed in patients with alcoholic cirrhosis than in non-alcoholic cirrhosis (34.4 vs. 14.3%, p less than 0.05). Mean endotoxin concentration was not significantly higher in cirrhotics with ascites or esophageal varices as compared with the subgroup without ascites or esophageal varices. The endotoxin concentration did not correlate with serum bilirubin, prothrombin concentration or serum enzyme activities. In patients with alcoholic liver disease, however, endotoxin concentration revealed a negative correlation (p less than 0.05) with the concentration of high density lipoprotein cholesterol. On admission endotoxin concentrations in alcoholics with fatty liver were similarly elevated as observed in alcoholic cirrhosis. In six out of 12 patients with fatty liver or alcoholic hepatitis, in whom a second sample of plasma was investigated after 6 to 8 days, endotoxemia was no longer detectable; in the remaining patients, the endotoxin concentration decreased markedly. The results indicate that, irrespective of the stage of liver disease, alcohol abuse favours the development of endotoxemia. They support the hypothesis that gut-derived endotoxins might play a role in the initiation and aggravation of alcohol-induced liver disease.
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PMID:Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay. 205 Sep 95

Persistent abnormalities of liver function tests occur in approximately 15% of home parenteral nutrition (HPN) patients and are associated with steatosis, steatohepatitis, and, rarely, fibrosis or cirrhosis. Approximately one-third of patients with gut failure on long-term HPN have low total and free plasma carnitine concentrations, and it has been suggested that a deficiency of L-carnitine may be responsible for the steatosis and steatohepatitis in HPN patients. To determine whether administration of L-carnitine is capable of reversing steatosis in HPN patients, 4 adult women on HPN for a mean of 53 mo (range 21-80 mo) were studied before and after 1 mo of intravenous L-carnitine supplementation (1 g/day). All patients had abnormalities in standard liver function tests and low total and free plasma carnitine values. The mean total and free plasma carnitine concentrations and the mean total hepatic carnitine concentration were reduced before supplementation and rose to normal values after treatment (27.4 +/- 2.3 to 35.5 +/- 3.1 nmol/ml, 19.4 +/- 2.8 to 25.7 +/- 2.5 nmol/ml, and 3.5 +/- 0.65 to 6.5 +/- 1.2 nmol/mg of noncollagen protein, respectively). However, there were no significant changes in mean serum aspartate aminotransferase and alkaline phosphatase levels (65 +/- 21 vs. 54 +/- 12 IU and 429 +/- 220 vs. 472 +/- 224 IU, respectively), plasma free fatty acids, plasma triglycerides, hepatic free fatty acid and triglyceride concentrations, or the grade of hepatic steatosis on light microscopy. These results suggest that carnitine deficiency is not a major cause of steatosis and steatohepatitis in patients receiving HPN.
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PMID:L-carnitine therapy in home parenteral nutrition patients with abnormal liver tests and low plasma carnitine concentrations. 312 32

In 41 patients with alcoholic liver disease, antibodies to 12 common Escherichia coli O antigens (expressed as number of O antibody reactions with an agglutination titre of greater than or equal to 40) and to immunoglobulins IgG, IgA, and IgM were studied for 8 weeks. In 18 patients (8 with cirrhosis, 10 with fatty liver) who continued drinking during this period no significant changes were found. In 23 patients (11 with cirrhosis, 12 with fatty liver) who stopped or reduced drinking, a significant decrease in the levels of E. coli O antibodies and IgA was found (p less than 0.05 and p less than 0.01, respectively). In these 41 patients and in an additional 43 patients with alcoholic liver disease the amount of E. coli O antibodies was compared with type of histological lesion. The levels of E. coli O antibodies were significantly higher in cirrhosis with alcoholic hepatitis (22 cases) than in cirrhosis without alcoholic hepatitis (17 cases) (p less than 0.05). In these 17 patients antibody levels were significantly higher than in 41 patients with fatty liver without alcoholic hepatitis (p less than 0.02). In all patients a significant correlation between the number of positive reactions to E. coli O antigens and serum IgA concentration was found (p less than 0.01). No microbes were cultured from the liver biopsies, and no E. coli O antigens were demonstrated in the liver tissue by immunohistochemistry. Our results support the hypothesis that the high levels of E. coli O antibodies in alcoholic liver diseases are due to failure of the liver to extract circulating antigens and gut-derived endotoxins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Escherichia coli antibodies in alcoholic liver disease. Correlation to alcohol consumption, alcoholic hepatitis, and serum IgA. 620 66

The main enzymes involved in orotic acid metabolism, orotate phosphoribosyltransferase and orotidine 5'-phosphate decarboxylase, are associated as a multienzyme complex (complex U) which is present in the liver of most vertebrate species. Orotic-acid-enriched diets produce increased pyrimidine synthesis which competes with purine synthesis for 5-phosphoribosyl diphosphate, resulting in decreased adenylate levels in liver cells. Inhibition of secretion of very low density lipoproteins and hepatic steatosis is then observed. In contrast, lipoproteins secretion by the intestine is not impaired and fat does not accumulate in enterocytes. The aim of this work was to investigate whether orotate is differently metabolized in gut and in liver thus explaining the lack of effect on the intestinal lipoproteins secretion. Complex U was found in appreciable amounts in rat, mouse and rabbit livers; the intestinal mucosa of the two last species contains a much lower level of multienzyme complex whereas in rat intestine its activity cannot be detected. Indeed, radioactive aspartate and orotate were not incorporated into intestinal cells RNA. The absence of orotate metabolisation by lack of orotate phosphoribosyltransferase and orotidine 5'-phosphate decarboxylase activity in rat intestine would explain why this organ, in contrast to the liver, is protected against disturbances of nucleotide metabolism and lipoproteins secretion induced by orotic-acid-supplemented diets.
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PMID:Metabolism of orotic acid: lack of orotate phosphoribosyltransferase in rat intestinal mucosa. 729 64

This study was designed to test the hypothesis that deprivation of enteral feeding contributes to the development of total parenteral nutrition (TPN)-induced hepatic dysfunction and that alterations of gut hormones are involved in its pathogenesis. Twenty-one adult Sprague-Dawley rats were randomized into three groups: group 1 received chow feeding ad libitum (288 kcal/kg per day); group 2 received dextrose-based TPN (320 +/- 5 kcal/kg per day); and group 3 received TPN (315 +/- 15 kcal/kg per day) plus chow feeding ad libitum (74 +/- 1 kcal/kg per day). After 7 days, portal blood was assayed for insulin, glucagon, gastrin, peptide YY, secretin, and vasoactive intestinal polypeptide; systemic blood for determination of liver function tests and serum lipid analysis. Liver biopsies were taken for histology and staining for fat, and the remainder of the livers were removed for tissue lipid analysis. TPN induced striking hepatic steatosis with prominent histologic changes and accumulation of lipids, mainly triglycerides and cholesterol ester, in the liver. Addition of enteral feeding to TPN-treated animals significantly reduced the histologic changes as well as lipid accumulation in the liver. Portal plasma levels of gastrin and peptide YY were reduced in animals maintained on TPN alone, with no change in secretin or vasoactive intestinal polypeptide levels. Enteral supplementation increased peptide YY levels in group 3, but not to normal, while gastrin secretion remained decreased. The serum triglyceride levels were decreased in both TPN groups; no differences were detected in the serum cholesterol levels or liver function tests.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of enteral feeding on hepatic steatosis induced by total parenteral nutrition. 816 98

The hepatotoxic effects of alcohol have been described in detail, but factors responsible for its hepatotoxicity have only partially been characterized. For example, it is known that chronic ethanol ingestion increases hepatotoxicity and produces fatty liver, hepatitis and cirrhosis. However, acute ethanol consumption reduces endotoxin hepatotoxicity. It now appears that Kupffer cells participate in several aspects of these phenomena. Previously, most studies on the effects of alcohol on liver function have focused chiefly on the hepatocyte. Recently, attention has been directed towards the effect of ethanol ingestion on Kupffer cell function, which is stimulated by gut-derived endotoxins (lipopolysaccharides) via mechanisms dependent on increased gut permeability and the possible relationship between Kupffer cells and alcohol-induced liver injury. Here we will review new evidence for the proposal that Kupffer cells and endotoxins play a pivotal role in hepatotoxicity following alcohol exposure, based on studies using the continuous intragastric enteral feeding model developed by Tsukamoto and French and an acute model developed by us.
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PMID:Role of Kupffer cells and gut-derived endotoxins in alcoholic liver injury. 1075 16

There have been numerous recent advances in the understanding of the mechanisms of alcoholic liver disease pathogenesis. Endotoxin-induced Kupffer cell activation plays a role in cytokine-mediated inflammatory changes in the liver, and this can be blocked by a diet high in saturated fat, by a diet containing lactobacillus, which does not produce endotoxin, by neomycin antibiotic sterilization of the gut, by eliminating Kupffer cells, or by removing tumour necrosis factor-alpha with antibody or by using tumour necrosis factor-alpha knockout mice. The fatty liver component is mainly the result of the nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide redox shift to the reduced state by ethanol oxidation generation of reduced nicotinamide adenine dinucleotide, although this too can be blocked by a diet high in saturated fat. Hepatocytic enlargement occurs due to ethanol-induced inhibition of the ubiquitin-proteasome pathway of cytoplasmic protein degradation and the retention of oxidized proteins in hepatocytes. The liver is scarred by stellate cells that have been activated by inflammatory cytokines and growth factors produced by activated Kupffer cells, and by bile ductule metaplasia. Mallory bodies and balloon cell degeneration develop through the ethanol-induced oxidative stress-protein kinase activation pathway, inhibition of phosphatase activity and inhibition of the ubiquitin-proteasome pathway.
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PMID:Mechanisms of alcoholic liver injury. 1079 86


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