Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The earliest and most reproduceable lesion associated with chronic alcohol abuse is fatty liver. In some alcoholics this may be superseded by alcoholic hepatitis, which may represent the link between the early lesion and cirrhosis. Alcoholic cirrhosis usually begins as a regular, monolobular variety, but is eventually transformed into an irregular, multilobular type. All stages of alcoholic liver injury have now been produced in the baboon, despite high protein and vitamin supplemented diets. Alcohol may therefore now be regarded as a direct hepatotoxin. Epidemiological studies have indicated that alcoholic liver injury begins with an intake of more than 80 g ethanol a day, and that cirrhosis is generally not seen with an intake of less than 160 g per day. The development of cirrhosis correlates with the total duration and amount of alcohol ingested. Complications of alcoholic cirrhosis include iron overload and primary hepatic carcinoma.
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PMID:Relation of alcoholic liver injury to cirrhosis. 4 93

Detection and exclusion of focal liver lesions is especially difficult in patients with diffuse liver disease. Magnetic resonance (MR) imaging may be particularly valuable in these patients. By judicious comparison of appropriate pulse sequences, normal and hypertrophic liver may be distinguished from atrophic, neoplastic, or otherwise abnormal hepatic parenchyma. Chemical shift (lipid-sensitive) techniques allow definitive identification of fatty liver, including focal fatty infiltration or focal sparing. T2-weighted and T2*-weighted images allow identification of iron overload, depicting malignancies as focal masses without iron. Analysis of signal intensity and internal morphology allows confident distinction between regenerative nodules and hepatocellular carcinoma in most instances, and allows diagnosis of early carcinoma within regenerative nodules. MR imaging provides capabilities for noninvasive characterization of liver tissue beyond those available with other noninvasive modalities.
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PMID:Focal manifestations of diffuse liver disease at MR imaging. 911 25

This review includes the initial experience with NMR imaging of the liver, spleen, and pancreas at the University of California, San Francisco, using a prototype 0.35 Tesla system. This experience shows great promise for detection of hepatic metastases using T1-weighted pulse sequences. T2-weighted pulse sequences appear sensitive for detecting cavernous hemangioma of the liver and may allow tissue specific discrimination of the benign lesion from cancer. NMR is also suitable for evaluating diffuse metabolic alterations and is sensitive and specific for the diagnosis of iron overload. Detection of fatty liver requires use of chemical shift techniques as conventional NMR imaging pulse sequences are relatively insensitive. Motion artifacts and lack of an effective bowel contrast agent limits imaging of the pancreas and retroperitoneum, where CT remains the procedure of choice. The normal spleen has longer T1 and T2 relaxation times than liver or pancreas and NMR has not been successful in diagnosing splenic metastases or lymphoma on a routine basis. We conclude that NMR imaging will be valuable in the diagnosis of focal liver disorders; until fast scan techniques and effective magnetic contrast agents are available for oral and/or intravenous use, other abdominal applications will remain limited.
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PMID:Nuclear magnetic resonance of the liver, spleen, and pancreas. 300 15

Experimental animal models of hepatitis, fatty liver, and hepatic iron overload were evaluated using a 3.5-kGauss nuclear magnetic resonance (NMR) imaging system. Increases in image intensity measurements and in T2 relaxation times equalled the sensitivity of histologic findings for the detection of early stages of hepatitis. A significant shift in T1 relaxation times characterized the early stages of hepatic necrosis. Liver triglyceride content correlated significantly with increases in NMR intensity measurements (p less than 0.01); however, changes in liver water content had a much greater influence on intensity, T1, and T2. Thus, it may be possible to distinguish hepatitis from benign fatty liver. Liver iron content correlated with decreases in NMR intensity measurements (p less than 0.001), and iron levels as low as 1.2 mg/g were detected. NMR may more specifically identify hepatocellular iron overload than do other techniques that do not distinguish hepatocellular from reticuloendothelial iron.
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PMID:Nuclear magnetic resonance imaging of experimentally induced liver disease. 619 64

Clinical evidence indicates that patients with iron overload are more susceptible to liver cell damage from alcohol than persons with normal iron stores. Iron may act as a co-factor to catalyze the lipid peroxidation induced by hepatotoxic compounds such as alcohol. To elucidate the role of iron in ethanol-induced hepatocellular damage, we developed a new experimental model in the rat. Following dietary carbonyl iron feeding for 8 weeks, animals were pair-fed a liquid ethanol diet for 4 weeks. In iron-fed animals the liver iron content was 6.4 vs. 0.5 micrograms Fe/mg protein in the controls. Blood alcohol concentrations were similar in all ethanol-fed animals. Serum alanine aminotransferase (ALT) levels were elevated to 269 +/- 49 U/l in the iron+alcohol group compared to 52 +/- 6 U/l in the other groups. There was a strong correlation between ALT levels and hepatic iron content in the ethanol-fed animals. Morphologically, the alcohol-fed rats displayed hepatic steatosis, whereas occasional inflammation and iron in Kupffer cells was seen in the iron+alcohol animals. Ultrastructurally, necrotic hepatocytes and cells phagocytosed by Kupffer cells were only encountered in the iron+alcohol group. Compared to controls, the liver content of hydroxyproline was significantly increased in the iron+alcohol group. No morphological evidence of fibrosis was noted. The present study demonstrates biochemical and morphological evidence of increased hepatocellular damage following the combination of iron and ethanol.
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PMID:Iron increases ethanol toxicity in rat liver. 844 9

Magnetic resonance imaging (MRI) relies on the physical properties of unpaired protons in tissues to generate images. Unpaired protons behave like tiny bar magnets and will align themselves in a magnetic field. Radiofrequency pulses will excite these aligned protons to higher energy states. As they return to their original state, they will release this energy as radio waves. The frequency of the radio waves depends on the local magnetic field and by varying this over a subject, it is possible to build the images we are familiar with. In general, MRI has not been sufficiently sensitive or specific in the assessment of diffuse liver disease for clinical use. However, because of the specific characteristics of fat and iron, it may be useful in the assessment of hepatic steatosis and iron overload. Magnetic resonance imaging is useful in the assessment of focal liver disease, particularly in conjunction with contrast agents. Haemangiomas have a characteristic bright appearance on T2 weighted images because of the slow flowing blood in dilated sinusoids. Focal nodular hyperplasia (FNH) has a homogenous appearance, and enhances early in the arterial phase after gadolinium injection, while the central scar typically enhances late. Hepatic adenomas have a more heterogenous appearance and also enhance in the arterial phase, but less briskly than FNH. Hepatocellular carcinoma is similar to an adenoma, but typically occurs in a cirrhotic liver and has earlier washout of contrast. The appearance of metastases depends on the underlying primary malignancy. Overall, MRI appears more sensitive and specific than computed tomography with contrast for the detection and evaluation of malignant lesions.
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PMID:Magnetic resonance imaging (MRI) and diseases of the liver and biliary tract. Part 1. Basic principles, MRI in the assessment of diffuse and focal hepatic disease. 1105 26

Advances in imaging technology and development of liver-specific contrast agents have significantly increased the role of radiology in the detection and characterization of processes diffusely involving the liver. Tailored magnetic resonance imaging (MRI) sequences allow an accurate detection of many storage and metabolic diseases, such as iron overload disorders and steatosis (fatty liver). Faster scanning techniques available with both computed tomography (CT) and MRI provide, by assessing contrast dynamics, sufficient information for the characterization of diffuse neoplastic and vascular disorders. Characteristic changes in attenuation on CT, signal intensity on MRI, and enhancing features can be used to diagnose specific diffuse diseases such as candidiasis, diffuse/multifocal hepatocellular carcinoma, and schistosomiasis. Although an overlap in imaging findings still exists, familiarity with the imaging features of uncommon disorders such as Wilson's disease, amyloidosis, and sarcoidosis may be diagnostic in the proper clinical setting. This review focuses on the current role of imaging in the detection and characterization of diffuse liver disorders. Recent developments that have amplified the role of noninvasive diagnostic evaluation of these conditions are especially highlighted.
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PMID:Imaging of diffuse liver disease. 1143 72

Insulin sensitivity (euglycemic clamp, insulin infusion rate: 40 mU. m(-2). min(-1)) was studied in 30 subjects with biopsy-proven nonalcoholic fatty liver disease (NAFLD), normal glucose tolerance, and a BMI <30 kg/m(2). Of those 30 subjects, 9 had pure fatty liver and 21 had evidence of steatohepatitis. In addition, 10 patients with type 2 diabetes under good metabolic control and 10 healthy subjects were studied. Most NAFLD patients had central fat accumulation, increased triglycerides and uric acid, and low HDL cholesterol, irrespective of BMI. Glucose disposal during the clamp was reduced by nearly 50% in NAFLD patients, as well as in patients with normal body weight, to an extent similar to that of the type 2 diabetic patients. Basal free fatty acids were increased, whereas insulin-mediated suppression of lipolysis was less effective (-69% in NAFLD vs. -84% in control subjects; P = 0.003). Postabsorptive hepatic glucose production (HGP), measured by [6,6-(2)H(2)]glucose, was normal. In response to insulin infusion, HGP decreased by only 63% of basal in NAFLD vs. 84% in control subjects (P = 0.002). Compared with type 2 diabetic patients, NAFLD patients were characterized by lower basal HGP, but with similarly reduced insulin-mediated suppression of HGP. There was laboratory evidence of iron overload in many NAFLD patients, but clinical, histological, and biochemical data (including insulin sensitivity) were not correlated with iron status. Four subjects were heterozygous for mutation His63Asp of the HFE gene of familiar hemochromatosis. We concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity. NAFLD may be considered an additional feature of the metabolic syndrome, with specific hepatic insulin resistance.
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PMID:Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. 1147 47

The role of HCV RNA levels and host factors in the severity of liver injury was studied. Enrolled were 298 consecutive liver biopsy-proven chronic hepatitis (CH) C patients (179 men; median age: 52 years, range 19-68; CH, 198; cirrhosis, 100) and 18 chronic hepatitis C with normal ALT. HCV genotypes were: 1a, 4.3%; 1b, 53%; 2a/c, 28%; 3a, 7%; 4, 1.3%, and mixed 6.4%. Serum HCV RNA levels were similar for all genotypes (median: 2.8 x 10(6) eq/ml; range <0.2-69). In patients with chronic hepatitis without cirrhosis, the serum HCV RNA levels reflected the grade of liver necroinflammatory activity (R = 0.45; P < 0.001) and the stage of fibrosis (R = 0.51; P < 0.001), regardless of age, gender, HCV genotype, hepatic steatosis, and hepatic iron overload. Patients with high serum HCV RNA levels (> or =3 x 10(6) eq/ml) had higher ALT values (P < 0.002) than those with lower HCV RNA levels. Patients with normal ALT showed low HCV RNA levels (median: 0.82 x 10(6) eq/ml) and histological features of minimal or mild chronic hepatitis. Cirrhotic patients showed significantly lower levels of viremia than those with chronic hepatitis with a similar HAI. The data of a subgroup of 62 patients with an established time of infection showed that for a similar duration of disease, patients with serum HCV RNA levels > or =3 x 10(6) eq/ml had a significantly higher fibrosis score than those with lower levels. HAI and fibrosis score were significantly higher in patients with HCV RNA levels > or =3 x 10(6) eq/ml and grade 3-4 steatosis than those with lower HCV RNA levels and steatosis grades. The data indicate that the liver damage is correlated with the HCV RNA levels and that a high viral load acts together with steatosis in accelerating the progression of liver injury.
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PMID:Serum HCV RNA levels correlate with histological liver damage and concur with steatosis in progression of chronic hepatitis C. 1150 67

The exact differential diagnosis of iron overload syndromes is mandatory as important therapeutic consequences may derive from a correct diagnosis, especially when hemochromatosis is present. To facilitate diagnostic and therapeutic decisions algorithms and probabilistic calculations based on different frequencies of clinical symptoms and typical laboratory findings of the diseases in question have been proposed. Overestimation and/or underestimation of clinical symptoms and/or laboratory findings in using such calculations, however, may lead to incorrect diagnosis and therapy as demonstrated in this case. We report on a 62-year-old patient with arthralgia, pathologic glucose metabolism, brown skin pigmentation and excessively elevated ferritin and transferrin saturation levels, which initially were interpreted as signs of the assumed underlying disease (hemo-chromatosis) based on a high initial suspicion level and further corroborated by Bayesian probability analysis yielding a probability 99.0 % for the presence of hemochromatosis. Because of this high probability and the patient's wish for treatment phlebotomy was started, but stopped after having obtained negative results of genetic testing and normal quantitative liver iron values. The diagnosis of hemochromatosis had to be revised and symptoms and laboratory findings of this patient were found to be compatible with chronic fatty liver and pathologically altered iron metabolism due to chronic alcohol intake which the patient has initially concealed. The joint pain was explained in terms of chronic degenerative bone destruction, the impaired glucose tolerance seen as the consequence of obesity and the skin pigmentation was ascribed to sun exposure due to the patient's outdoor activities as a hobby farmer not evaluated during initial presentation. The implications and importance of unbiased history taking, critical interpretation of clinical symptoms and laboratory findings in using probabilistic calculations and diagnostic decision analysis are emphasized and the different mechanisms of iron metabolism in hemochromatosis and hemosiderosis are discussed.
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PMID:[Hemochromatosis or hemosiderosis? Initial misinterpretation of clinical symptoms and laboratory findings in a 62-year-old patient]. 1196 34


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