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)

We investigated the hepatocellular peroxisomes in 27 patients with steatosis of the liver by means of catalase cytochemistry, light and electron microscopic study, and morphometry. Seven normal human livers were used as controls. In our patients, fatty liver was mainly associated with alcohol abuse or obesity. Indications for a slight decrease in catalase activity and for a proliferation were found in visual evaluation of the peroxisomes. Morphometric analysis showed a significant decrease in mean peroxisomal diameter (to 87%) and a simultaneous significant elevation to numerical density of the peroxisomes (to 188%); this resulted in a normal volume density and a significant increase to (133%) in surface density. However, individual differences were found. No differences in peroxisomal characteristics were found between fatty livers of different causes. A significant inverse linear correlation between mean peroxisomal diameter and numerical density was found in patients with fatty livers. Because a similar correlation was also found when control data were added to the fatty liver data, we hypothesize that the peroxisomal compartment in human fatty livers is adapted in such a way to permit the same metabolic efficiency as in control livers.
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PMID:Alterations of peroxisomes in steatosis of the human liver: a quantitative study. 765 78

Localized proton MR spectroscopy using stimulated echoes was used to quantify the liver fat concentration in patients with various degrees of fatty liver due to alcohol abuse. Ten patients underwent a liver biopsy followed by chemical triglyceride estimation of the fatty content. A statistically significant correlation was found between the fat concentration measured in the liver biopsies, and the concentration calculated from the spectroscopic experiments (r = 0.9, p < .001). Quantitative assessment of liver fat concentrations using localized spectroscopy is superior to methods based on differences in relaxation times, and can be used to estimate the fat concentration over the full range of fat content in contrast to the spectroscopic imaging methods. Localized spectroscopy may replace liver biopsy in the diagnosis of diffuse fatty infiltrations, and can be used for follow-up, due to its noninvasive nature.
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PMID:Quantification of liver fat using magnetic resonance spectroscopy. 800 79

Non-alcohol-induced steatohepatitis (NASH) is characterized by elevated serum aminotransferase activities with hepatic steatosis, inflammation, and occasionally fibrosis that may progress to cirrhosis. No established treatment exists for this potentially serious disorder. Our aim was to conduct a pilot study to evaluate the safety and estimate the efficacy of ursodeoxycholic acid (UDCA) and clofibrate in the treatment of NASH. Forty patients were diagnosed with NASH based on a compatible liver biopsy with other causes of liver disease, including alcohol abuse, excluded by history, serum tests, and use of ultrasound. Twenty-four patients received 13 to 15 mg/kg/d of UDCA for 12 months. Sixteen patients with hypertriglyceridemia were placed on clofibrate, 2 g/day for 12 months. Twenty-five women and 15 men entered the study. Six of 40 patients (15%) withdrew because of side effects. Four additional patients were withdrawn because of noncompliance; one of them later required liver transplantation. In the UDCA group, the decreases in mean serum levels of alkaline phosphatase, alanine transaminase (ALT), and gamma-glutamyl transpeptidase (GGT) as well as histological grade of steatosis were significant. Among the patients treated with clofibrate, no change from baseline was found in mean ALT, aspartate transaminase (AST), GGT, bilirubin, triglycerides, and cholesterol, or in histological grade of steatosis, inflammation, or fibrosis after 12 months of treatment as compared with entry. Alkaline phosphatase activities decreased significantly from baseline. Despite the known lipid-lowering effects of clofibrate, it did not appear to be of clinical benefit in the treatment of NASH in this 1-year pilot study. However, treatment of NASH with UDCA for 12 months resulted in significant improvement in alkaline phosphatase, ALT, GGT, and hepatic steatosis. The possible benefit of UDCA therapy should be further investigated in the context of a randomized, controlled trial.
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PMID:Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis: a pilot study. 867 65

Alcoholic liver disease evolves from fatty change through alcoholic hepatitis to alcoholic cirrhosis. Its development is associated with an excess mortality both in relation to the presence of liver disease and to other complications of alcohol abuse. In the majority of patients fatty liver is a benign lesion which will reverse completely following abstinence from alcohol. Continued drinking is associated with the eventual development of cirrhosis in approximately 20% of individuals. Survival rates of 70% are reported both at 2 years and at 10 years. Alcoholic hepatitis is a precirrhotic lesion; progression to cirrhosis is observed more commonly in women, in individuals with severe disease and in those who continue to drink. Thirty-day mortality rates of less than 20% are observed in patients with mild to moderate disease but exceed 40% in individuals with severe liver injury. Corticosteroids may improve short term survival in a small subgroup of patients with severe alcoholic hepatitis. Survival rates of 55 to 60% are reported both at 2 years and at 10 years. Survival is significantly reduced in women and in the elderly and is adversely affected by the presence of severe liver injury, evolution to cirrhosis and continued drinking. Two-thirds of patients with alcoholic cirrhosis present with decompensated disease; 15% will develop hepatocellular carcinoma. Survival rates at 5 years vary from zero to 80%; 60 to 90% of individuals die of their liver disease. Survival is adversely affected by the presence of decompensated disease, superimposed alcoholic hepatitis, continued drinking and the development of hepatocellular carcinoma. The advent of hepatic transplantation, which has a 5-year survival rate in excess of 70%, will influence these survival figures.
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PMID:The prognosis and outcome of alcoholic liver disease. 897 53

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

For the first time in history, populations in affluent countries may concomitantly indulge in rich food and physical idleness. Various combinations of obesity, diabetes, and hypertriglyceridemia, with insulin resistance as the common feature, cause hepatic steatosis, which can trigger necroinflammation and fibrosis. Patients with "primary" steatohepatitis exhibit ultrastructural mitochondrial lesions, decreased activity of respiratory chain complexes, and have impaired ability to resynthesize ATP after a fructose challenge. Mitochondria play a major role in fat oxidation and energy production but also leak reactive oxygen species (ROS) and are the main cellular source of ROS. In patients with steatosis, mitochondrial ROS may oxidize hepatic fat deposits, as suggested in animal models. Lipid peroxidation products impair the flow of electrons along the respiratory chain, which may cause overreduction of respiratory chain components, further increasing mitochondrial ROS formation and lipid peroxidation. Another vicious circle could involve ROS-induced depletion of antioxidants, impairing ROS inactivation. Blood vitamin E is decreased in some obese children with steatohepatitis, and serum transaminases improve after vitamin E supplementation. Steatohepatitis is also caused by alcohol abuse, drugs, and other causes. In "secondary" steatohepatitis, mitochondrial ROS formation is further increased as the causative disease itself directly increases ROS or first impairs respiration, which secondarily increases mitochondrial ROS formation. This "second hit" could cause more lipid peroxidation, cytokine induction, Fas ligand induction, and fibrogenesis than in primary steatohepatitis.
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PMID:Mitochondria in steatohepatitis. 1129 97

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

We report an autopsy case of fatal acute alcoholism showing myoglobinuria and myocardial damage. The victim was a 29-year-old male, who was found drunk at his home. Although he was once brought to a hospital following a police officer's advice, he was taken into custody without effective medical care due to his violent behavior, and died about 16 hours later. Autopsy revealed marked congestion of the viscera and fatty liver. Histologically, skeletal muscle and myocardium showed focal degeneration and necrosis. Immunohistochemical investigation revealed a diffuse myoglobin loss from muscle fibers. Alcohol concentrations were 0.54 mg/ml, 0.79 mg/ml and 2.53 mg/ml in the left, right heart blood and urine, respectively. No other drugs or poisons were detected. The urine was dark brown, showing marked myoglobinuria. Cardiac troponin T, I and CK-MB in the pericardial fluid showed elevated levels even when postmortem influence was taken into consideration. From these observations, the cause of death was determined as myocardial damage from advanced acute alcoholic myopathy accompanied by myoglobinuria, possibly with underlying alcohol abuse. The present case suggests that careful clinical observation and adequate management are essential for an alcoholic patient with neurological symptoms.
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PMID:[Acute alcoholism with myoglobinuria: an autopsy case report]. 1271 45

Fatty liver disease that develops in the absence of alcohol abuse is recognized increasingly as a major health burden. This report summarizes the presentations and discussions at a Single Topic Conference held September 20-22, 2002, and sponsored by the American Association for the Study of Liver Diseases. The conference focused on fatty liver disorders. Estimates based on imaging and autopsy studies suggest that about 20% to 30% of adults in the United States and other Western countries have excess fat accumulation in the liver. About 10% of these individuals, or fully 2% to 3% of adults, are estimated to meet current diagnostic criteria for nonalcoholic steatohepatitis (NASH). Sustained liver injury leads to progressive fibrosis and cirrhosis in a fraction, possibly up to one third, of those with NASH, and NASH may be a cause of cryptogenic cirrhosis. NASH is now a significant health issue for obese children as well, leading to cirrhosis in some. The diagnostic criteria for NASH continue to evolve and rely on the histologic findings of steatosis, hepatocellular injury (ballooning, Mallory bodies), and the pattern of fibrosis. Generally recognized indications for biopsy include establishing the diagnosis and staging of the injury, but strict guidelines do not exist. Liver enzymes are insensitive and cannot be used reliably to confirm the diagnosis or stage the extent of fibrosis. Older age, obesity, and diabetes are predictive of fibrosis. The pathogenesis of NASH is multifactorial. Insulin resistance may be an important factor in the accumulation of hepatocellular fat, whereas excess intracellular fatty acids, oxidant stress, adenosine triphosphate (ATP) depletion, and mitochondrial dysfunction may be important causes of hepatocellular injury in the steatotic liver. Efforts are underway to refine the role of insulin resistance in NASH and determine whether improving insulin sensitivity pharmacologically is an effective treatment. An altered lifestyle may be a more effective means of improving insulin sensitivity. The research agenda for the future includes establishing the role of insulin resistance and abnormal lipoprotein metabolism in NASH, determining the pathogenesis of cellular injury, defining predisposing genetic abnormalities, identifying better noninvasive predictors of disease, and defining effective therapy.
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PMID:Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. 1271 2

Increased oxidative stress and lipid peroxidation (LPO) are implicated in multistage carcinogenesis. Recent studies have shown that LPO-derived reactive hydroxyalkenals can form promutagenic exocyclic etheno-DNA adducts in vivo. Such DNA damage was found to be increased in the liver of patients with metal storage diseases and in colon adenomas of familial adenomatous polyposis patients. We now have investigated the levels of 1,N(6)-ethenodeoxyadenosine (epsilon dA) in human liver samples obtained from a group of patients diagnosed with hepatitis, fatty liver, fibrosis and cirrhosis, primary hemochromatosis and Wilson's disease. Using an immunohistochemical method, the relative mean pixel intensity of randomly selected nuclei was measured by imaging software; positively stained cell nuclei (arbitrary mean pixel intensity > or =0.5) were counted. Prevalence of epsilon dA (%) was calculated from the ratio of a number of positively stained cell nuclei over a total number of cells counted. When compared with normal livers (3.1%), the percent prevalence (means) was significantly higher in specimens of alcoholic fatty liver (15%) and fibrosis patients (50%) but not in samples with hepatitis (induced by various factors) (6.2%). The percent prevalence in alcohol fibrosis was as high as in the liver from Wilson's disease (50.7%) and hemochromatosis (33%) patients. This is the first demonstration of increased epsilon dA in human liver diseases due to alcohol abuse. We conclude that excessive hepatic DNA damage, as assessed by miscoding etheno-DNA adduct in the nuclei of liver biopsies, is probably caused by alcohol-induced oxidative stress and LPO. In cancer-prone liver diseases (fatty liver, cirrhosis/fibrosis) such damage may act as a driving force towards malignancy.
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PMID:Immunohistochemical detection of 1,N6-ethenodeoxyadenosine in nuclei of human liver affected by diseases predisposing to hepato-carcinogenesis. 1474 17


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