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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver cirrhosis is often accompanied by a disturbed carbohydrate metabolism similar to type 2 diabetes. To investigate the severity of the defect in insulin secretion in this form of diabetes, we measured insulin release from isolated pancreatic islets of rats with CCl(4)-phenobarbital-induced liver cirrhosis. Cirrhosis was confirmed by clinical signs, elevated liver enzymes and histology. Fasting venous plasma glucose concentrations were equal in rats with liver cirrhosis and in controls. Plasma insulin and glucagon concentrations were significantly greater (P<0.01) in cirrhotic rats than in control animals. Glucose (16.7 mM)-induced stimulation of insulin release from pancreatic islets revealed a twofold increase in control and cirrhotic rats. Basal and stimulated insulin secretion, however, were significantly lower in cirrhotic animals. The incretin hormone, glucagon-like peptide-1 (GLP-1), has therapeutic potential for the treatment of type 2 diabetes. Therefore, islets from control and cirrhotic animals were incubated with GLP-1 in concentrations from 10(-)(11) to 10(-)(6) M. GLP-1 stimulated insulin release in a concentration-dependent manner. In islets from cirrhotic rats, basal and stimulated insulin secretion was blunted compared with controls. These data show that the hyperinsulinemia observed in liver cirrhosis is not due to an increase of insulin secretion from islets, but could be explained by decreased hepatic clearance of insulin. GLP-1 may ameliorate diabetes in patients with liver cirrhosis.
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PMID:Insulin secretion defects in liver cirrhosis can be reversed by glucagon-like peptide-1. 1060 33

Nonalcoholic steatohepatitis (NASH) is a histological diagnosis applied to a constellation of liver biopsy findings that develop in the absence of alcohol abuse. Steatosis, a mixed cellular inflammatory infiltrate across the lobule, evidence of hepatocyte injury and fibrosis are the findings that can be seen. This entity is often identified during evaluation of elevated aminotransferases after exclusion of viral, metabolic and other causes of liver disease. Obesity is a major risk factor for NASH. The role of diabetes is less certain, although evidence is accumulating that hyperinsulinism may play an important pathophysiological role. Patients sometimes suffer from right upper quadrant abdominal pain and fatigue; examination may reveal centripetal obesity and hepatomegaly. Although patients are often discovered because of persistent aminotransferase elevations, these enzymes can be normal in NASH. When they are elevated, the alanine aminotransferase level is typically significantly greater than the aspartate aminotransferase level. This can be particularly helpful for excluding occult alcohol abuse. Imaging studies identify hepatic steatosis when the amount of fat in the liver is significant; however, imaging does not distinguish benign steatosis from NASH. Ultimately a liver biopsy is needed to diagnose NASH. The biopsy may be useful for establishing prognosis based on the presence or absence of fibrosis and for excluding other unexpected causes of liver enzyme elevations. Weight loss is the mainstay of treatment for obese patients. About 15% to 40% of NASH patients develop fibrosis; how many of these cases progress to cirrhosis is unknown, but about 1% of liver transplants are performed with a pretransplant diagnosis of NASH.
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PMID:Nonalcoholic steatohepatitis: an evolving diagnosis. 1079 85

Fatty liver is a relatively common incidental finding on imaging studies. Although generally a benign condition, fat in the liver can be troubling for clinicians because it can cause persistently elevated liver enzyme levels. The finding of fatty liver may also indicate the presence of nonalcoholic steatohepatitis (NASH). NASH is a histologic diagnosis applied to a constellation of liver biopsy findings that appear similar to alcoholic liver disease but are found in the absence of alcohol abuse. NASH is typically identified during the evaluation of elevated aminotransferase levels after exclusion of viral, metabolic, and other causes of liver disease. Obesity is a major risk factor; the role of diabetes is less certain, although evidence is accumulating that hyperinsulinism may play an important pathophysiologic role. About 15% to 40% of NASH patients develop hepatic fibrosis, a precursor to cirrhosis. Exactly how many patients with NASH progress to cirrhosis is unknown, but 1% to 2% of liver transplants are now performed because of a pretransplant diagnosis of NASH. Specific and effective treatments are needed but until the pathogenesis of this common liver disease is better understood, weight loss will remain the mainstay of treatment for obese patients.
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PMID:Fatty liver and nonalcoholic steatohepatitis. 1150 Nov 94

Nonalcoholic steatohepatitis (NASH) is increasingly recognized as a relatively prevalent disorder (ie, occurring in 3% of adults) that may progress to cirrhosis in 15% to 40% of those who are afflicted. NASH is a subset of a broader diagnostic category, nonalcoholic fatty liver disease, a term applied to a condition involving the presence of excess fat in the liver with or without inflammation and cellular injury. A diagnosis of NASH is established by the presence of morphologic changes on liver biopsy similar to those seen in alcoholic hepatitis, including hepatocellular fat accumulation, evidence of lobular inflammation and cell injury, and in some cases, progressive fibrosis. Obesity and type 2 diabetes, two conditions associated with insulin resistance, are major risk factors for the development of NASH. Accumulating evidence suggests that the hyperinsulinemia associated with insulin resistance may be important in the pathogenesis of NASH. Clinical trials will now determine whether treatment of insulin resistance is an effective therapy for NASH.
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PMID:Evolving pathophysiologic concepts in nonalcoholic steatohepatitis. 1182 39

Although glucose intolerance and/or overt diabetes are common in cirrhotic subjects, the mechanism(s) that lead to post-prandial hyperglycemia in cirrhosis are not entirely known. To this aim, we measured whole-body rates of glucose appearance (Ra) and of disappearance (Rd) in cirrhotic-diabetic subjects and in controls, before and following a 4-hr administration of a mixed meal. In the post-prandial phase, endogenous and dietary glucose Ra, as well as first-pass splanchnic uptake of dietary glucose, were measured using a double (ie oral and intravenous) glucose tracer technique. In the fasting state, the cirrhotic patients were hyperglycemic (12.0 +/- 1.4 vs 4.4 +/- 0.2 mmol/l in controls, p < 0.001), had a higher glucose Ra (17.0 +/- 2.7 vs 10.2 +/- 0.5 micromol x kg(-1) x min(-1), p < 0.05) and a lower clearance rate (1.51 +/- 0.19 vs 2.32 +/- 0.06 ml x kg x min, p < 0.02). Following the meal, plasma glucose increased to greater values (p < 0.002) in the patients (to 16.8 +/- 2 mmol/l, mean values of the last 40 min) than in the controls (to 7.2 +/- 0.4 mmol/l). Insulin increased in both groups but it was 35% lower (p > 0.05) in the patients. Post-prandial total glucose Ra (cirrhotics: 21.3 +/- 2.6; controls: 19.2 +/- 1.4 pmol x kg(-1) x min(-1)), endogenous Ra (cirrhotics: 7.3 +/- 1.5; controls: 7.0 +/- 1.3 micromol x kg(-1) x min(-1)) and first-pass splanchnic uptake of dietary glucose (cirrhotics: 9.8 +/- 2.6; controls: 11.5 +/- 1.6 micromol x kg x min(-1)), were not different between the 2 groups, whereas glucose clearance remained lower (p<0.001) in the patients (1.31 +/- 0.25 ml x kg(-1) x min)-1)) than in the controls (2.72 +/- 0.26). These data demonstrate that, in cirrhotic-diabetic patients, post-pran-dial hyperglycemia is not due to a reduced extraction of dietary glucose nor to an increased endogenous production, but rather to a defect in peripheral glucose clearance, secondary to either insulin-resistance and/or relative insulin deficiency.
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PMID:Glucose kinetics and splanchnic uptake following mixed meal ingestion in cirrhotic-diabetic subjects. 1185 63

Hyperinsulinaemia and reduced insulin sensitivity are common features in patients with cirrhosis. Octreotide, a long-acting somatostatin analogue, is used in cirrhotic patients in the treatment of bleeding oesophageal varices. Octreotide has potent effects on the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis in healthy subjects. but the effects on the GH/IGF-I axis in patients with cirrhosis have been described only briefly. The effects of a 12 h infusion of octreotide (bolus 0.75 microg/kg followed by 0.75 microg/kg/h) in 25 subjects (normals n=9, compensated cirrhotics n=8, decompensated cirrhotics n=8) were compared with those in placebo-treated controls (n=19) during fasting conditions. IGF-I, free IGF-I, IGF binding proteins (IGFBPs), insulin, C-peptide, GH and glucose were measured. Insulin resistance was calculated using the HOMA method. Octreotide reduced levels of total IGF-I in patients with compensated cirrhosis (p=0.03) and free IGF-I in decompensated cirrhosis (p<0.01). Insulin resistance was significantly reduced in normal subjects. whereas the reduction in insulin resistance did not reach statistical significance in patients with cirrhosis. In normal subjects, octreotide increased the IGFBP-1 area under curve threefold (p<0.01) and decreased IGFBP-3 levels (p<0.01), but these effects were blunted in the cirrhotic patients. Similarly, the reduction of insulin and C-peptide was blunted in the cirrhotic patients, whereas a significant reduction in GH was demonstrated in all groups. The effects of octreotide on the GH/IGF-I axis are mitigated in patients with cirrhosis and this may be a reflection of relative hyperinsulinaemia during octreotide treatment in these patients.
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PMID:Effects of octreotide on serum insulin-like growth factor I and insulin-like growth factor binding proteins in patients with cirrhosis. 1200 12

Endothelins are powerful vasoconstrictor agents produced by endothelial cells and identified by Yanagisawa et al. in 1988. Two types of receptors for endothelins have been identified: ET(A) receptors are located on smooth muscle cells of the vascular wall and are responsible for endothelin-induced vasoconstriction while ET(B) receptors are located on endothelial cells and induce these cells to release NO and prostacyclin. Moreover, these peptides not only cause a potent and prolonged vasoconstriction but are also known to enhance cell proliferation and to stimulate extracellular matrix accumulation. High levels of plasma or tissue endothelins have been found in patients with heart failure, diabetes, stroke, primary pulmonary hypertension, liver cirrhosis and other diseases. Given these effects of endothelins, blocking their receptors might be a new way to reduce blood pressure and to treat other illnesses. Accordingly, many endothelin antagonists have been developed and evaluated in animals and humans. Enrasentan is a mixed ET(A) and ET(B) receptor antagonist with a higher affinity for ET(A) receptors, although it cannot be considered a selective antagonist. In an animal model of hypertension and cardiac hypertrophy the drug has reduced blood pressure, prevented cardiac hypertrophy and preserved myocardial function. In rats with hyperinsulinemia and hypertension enrasentan normalized blood pressure and prevented cardiac and renal damage. In rats with stroke the drug reduced the ischemic area in the brain. Enrasentan has been added to conventional treatment in patients with heart failure (NYHA Class 2-3) and no addictive effect of the drug has been observed. This is in contrast with results obtained in animal models and still has not been explained. In conclusion, many possible clinical applications can be suggested for this drug, but further studies are necessary to better evaluate its therapeutic efficacy.
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PMID:Enrasentan, an antagonist of endothelin receptors. 1259 14

Nonalcoholic steatohepatitis (NASH) is one entity in a spectrum of chronic liver disease related to obesity, hyperinsulinemia, insulin resistance, and liver cell injury from free fatty acid toxicity or other oxidant stress. The more inclusive term "nonalcoholic fatty liver disease" (NAFLD) is increasingly being used to encompass the entire spectrum, which includes simple hepatic steatosis without inflammation (which may not lead to progressive liver injury), NASH itself, and the resulting cirrhosis (which may be devoid of steatosis). Children get NAFLD, and the incidence of this pediatric liver disease is rising as childhood obesity becomes increasingly prevalent. Although much remains to be learned about pediatric NAFLD, it is already evident that children with NASH risk progressive liver damage, including cirrhosis. Liver biopsy is required for definitive diagnosis, and other causes of fatty liver in childhood must be excluded. Gradual weight loss through increased regular exercise and a low-fat, low-refined carbohydrate diet appears to be effective. Drug treatments are being developed. Pediatric NASH is a serious complication of childhood obesity.
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PMID:Nonalcoholic steatohepatitis in children. 1273 49

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of disorders that encompasses simple hepatic steatosis and the more serious nonalcoholic steatohepatitis (NASH) that can progress to cirrhosis. Although the prevalence of NAFLD in childhood is not clear, it is apparently more common than originally thought. The major association with NAFLD is obesity, and as the prevalence of obesity in childhood and adolescence increases, fatty liver is recognized with greater frequency. Although the factors associated with progression of liver disease have not been determined fully, the pathogenesis of NASH is a "two hit" process that includes disturbed lipid homeostasis, resistance to the effects of insulin and subsequent hyperinsulinemia, and local toxic effects of triglyceride on hepatocytes. Treatment options are currently limited.
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PMID:Nonalcoholic fatty liver disease. 1527 63

Nonalcoholic fatty liver disease (NAFLD) is the preferred term to describe the spectrum of liver damage ranging from hepatic steatosis to steatohepatitis, liver fibrosis, and cirrhosis, and it is emerging as the most common liver disease in industrialized countries. Thus, the discovery of food components that would ameliorate NAFLD is of interest. Conjugated linoleic acid (CLA), a mixture of positional and geometric isomers of linoleic acid, has attracted considerable attention because of its potentially beneficial biological effects both in vitro and in vivo. We tested whether dietary CLA protects Zucker (fa/fa) rats from hepatic injury. After 8 wk of feeding, hepatomegaly, hepatic triglyceride (TG) accumulation, and elevated hepatic injury markers in plasma were markedly alleviated in CLA-fed Zucker rats compared with linoleic acid-fed (control) rats. These effects were attributed in part to the enhanced hepatic activities of carnitine palmitoyltransferase, a key enzyme of fatty acid beta-oxidation, and microsomal TG transfer protein, an important factor for lipoprotein secretion due to the CLA diet. We previously reported that the severe hyperinsulinemia in control Zucker rats was attenuated in CLA-fed rats due to an enhanced level of plasma adiponectin, which improves insulin sensitivity. In the present study, the adiponectin concentration was increased and the mRNA expression of tumor necrosis factor-alpha, an inflammatory cytokine, was markedly suppressed in the liver of CLA-fed Zucker rats. We speculate that the enhanced level of liver adiponectin may prevent the development and progression of NAFLD in CLA-fed Zucker rats.
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PMID:Dietary conjugated linoleic acid alleviates nonalcoholic fatty liver disease in Zucker (fa/fa) rats. 1562 25


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