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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 21 patients with liver cirrhosis, 35 normal subjects, 8 patients with chemical and 11 with manifest diabetes 0.5 g glucose/kg together with 14C-glucose were injected intravenously. 71% of the cirrhotics showed an impaired glucose tolerance. IRI response was exaggerated. The insulinogenic index was elevated in patients with liver cirrhosis and normal glucose tolerance and normal or subnormal in those with carbohydrate intolerance, as well as in diabetics. Decrease of the specific activity of glucose, expressing supply of non-labelled glucose to the body pool, was much more rapid in patients with carbohydrate intolerance, either hepatogenic or not, when compared at equal glucose concentrations. Moreover all groups with deteriorated glucose tolerance exhaled less 14CO2. Consequently, diabetes in chronic liver disease displays the same abnormalities as diabetes in obesity with respect to liver glucose supply and glucose oxidation. In both conditions diminished glucose assimilation is usually the result of reduced removal and increased supply. Therefore it is concluded that impaired hepatic uptake of glucose cannot be implicated as a single cause of hepatogenic diabetes.
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PMID:[Insulin resistance and blood glucose replacement rates in liver cirrhosis. Studies with 14C-glucose (author's transl)]. 90 3

Twenty-six patients are described who had otherwise unexplained hepatitis after halothane anaesthesia. Twenty-four (92 per cent) had multiple exposures, and 11 (42 per cent) died. In eight patients a characteristic pattern of delayed postoperative pyrexia has been found. Obesity was common, but the clinical features and complications were those of any severe hepatitis. Obesity, early onset of jaundice after anaesthesia, and low thrombotest, were associated with a fatal outcome. None of those who were followed up after recovery developed clinical or biochemical evidence of chronic liver disease. The differential diagnosis of postoperative jaundice is discussed, and it is shown that halothane patients with hepatic encephalopathy are significantly older (25.4 plus or minus 11.6 years) than those referred to this unit with viral hepatitis of equal severity (34.1 plus or minus 16.4 years). Unexplained jaundice or delayed pyrexia after a previous administration of halothane should be a contraindication to its further use.
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PMID:Halothane-related hepatitis. A clinical study of twenty-six cases. 115 92

Although transjugular liver biopsy requires the availability of trained personnel, takes more time than percutaneous biopsy and is moderately expensive, it is a safe alternative technique for obtaining adequate liver tissue for diagnosis in special clinical situations. The usual indications for transjugular rather than percutaneous liver biopsy are (a) coagulation disorder (prothrombin time greater than 3 sec over control value and/or platelet count less than 60,000/cm3), (b) massive ascites and (c) desire to perform ancillary procedures, such as measurement of pressures or opacification of the hepatic veins and inferior vena cava. Less common indications for transjugular liver biopsy include failed percutaneous biopsy, massive obesity, small cirrhotic liver (increased risk and lower success rate) and suspected vascular tumor or peliosis hepatis. Results from several centers indicate that adequate or diagnostic liver tissue is obtained in 81% to 97% of cases. The typical length of the biopsy core ranges from 0.3 cm to 2.0 cm. Modification of the classic technique, particularly the adaptation of a Tru-Cut needle, shows promise in yielding longer cores of tissue with less fragmentation. Transjugular liver biopsy is performed with an acceptable complication rate that ranges 0% to 20%. The reported mortality of transjugular liver biopsy was 0 in three major centers and ranged from 0.1% to 0.5% in three other centers. Transjugular liver biopsy may be useful in obtaining diagnostic liver tissue not only in advanced chronic liver disease with coagulopathy, ascites or both, but also in patients with fulminant hepatic failure to better determine prognosis and the need for liver transplantation.
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PMID:Transjugular liver biopsy. 155 49

A 54-year-old woman with obesity, type II diabetes mellitus, hyperlipidemia, and massive hepatomegaly was found to have severe steatosis and cirrhosis on liver biopsy. Complete evaluation led to the diagnosis of fatty cirrhosis associated with obesity and diabetic mellitus. She underwent four months of fasting with a protein-carbohydrate and vitamin-mineral liquid supplement to control her weight and metabolic abnormalities and to evaluate the effect of this diet on her liver disease. She lost 40 pounds to ideal body weight, normalized her serum glucose and lipids, and decreased total liver height by one third. Liver biopsy at the completion of her diet showed inactive cirrhosis and complete resolution of steatosis. Supplemented fasting with only modest weight loss can safely resolve fatty liver in obese diabetics with nonalcoholic steatosis and cirrhosis. Aggressive dietary approaches to achieve long-term weight loss deserve study in this subgroup of diabetics with unexplained chronic liver disease.
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PMID:Steatosis and cirrhosis in an obese diabetic. Resolution of fatty liver by fasting. 382 84

A common reason for referring patients to hepatologists is persistently abnormal serum transaminase levels with vague constitutional symptoms. In the United Kingdom, these abnormalities are most often caused by a fatty liver either related to obesity or alcohol abuse; they are less commonly caused by chronic liver disease, particularly chronic viral hepatitis, autoimmune hepatitis, or chronic biliary disease. Endocrine disease is rarely a cause of these abnormalities, although hypothyroidism and hyperthyroidism are well-recognized causes. Addison's disease has been only reported once in the literature by R. G. Olsson as a cause of increased transaminase levels associated with constitutional symptoms; it is not mentioned in textbooks on hepatology. Three patients with Addison's disease are reported here, all of whom had increased serum transaminase levels for more than 6 months before the recognition of the hypoadrenalism with resolution to normal after steroid replacement. Hepatologists should consider subclinical Addison's disease as a cause of persistently increased transaminase levels with constitutional symptoms in the absence of evidence for fatty liver as well as viral and autoimmune markers.
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PMID:Subclinical Addison's disease: a cause of persistent abnormalities in transaminase values. 755 2

Nonalcoholic steatohepatitis, along with other forms of nonalcoholic fatty liver disease, is a chronic liver disease that is attracting increasing significance. It is a clinicopathologic syndrome that was originally described in obese, diabetic females who denied alcohol use but in whom the hepatic histology was consistent with alcoholic hepatitis. This typical patient profile has been expanded and is now recognized to occur even in normal weight males without overt abnormalities in carbohydrate metabolism. Although originally believed to be a benign clinical entity, nonalcoholic steatohepatitis is now recognized as a cause of progressive fibrotic liver disease with adverse clinical sequelae. It is important to emphasize that nonalcoholic steatohepatitis is best considered one type of a larger spectrum of nonalcoholic fatty liver disease that is a consequence of insulin resistance and ranges from fat alone to fat plus inflammation, fat plus ballooning degeneration, and nonalcoholic steatohepatitis, the latter being the most serious form. As with any disease, the clinical importance of nonalcoholic steatohepatitis is related to its prevalence and natural history. Recent studies using different methodologies indicate that in the general population the prevalence of fatty liver and nonalcoholic steatohepatitis is approximately 20% and 3%, respectively. These prevalence rates are increased in certain subpopulations such as obesity and type II diabetes. Of greater concern is the recognition that cirrhosis and liver-related deaths occur in approximately 20% and 8% of these patients, respectively, over a 10-year period. Risk factors for these adverse clinical symptoms include patients older than the age of 45, the presence of diabetes or obesity, an aspartate aminotransferase/alanine aminotransferase ratio > 1 and hepatic histology. However, a number of important unresolved issues must be clarified before the true natural history of this disease can be fully understood.
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PMID:Clinical features and natural history of nonalcoholic steatosis syndromes. 1129 93

The definable causes of nonalcoholic steatohepatitis (NASH) include jejunoileal bypass surgery (JIB), other causes of rapid and profound weight loss in obese subjects, total parenteral nutrition, drugs, industrial toxins, copper toxicity, and disorders characterized by extreme insulin resistance. However, the etiopathogenesis in most cases of NASH appears multifactorial. Obesity, type 2 diabetes, and hypertriglyceridemia are often associated with hepatic steatosis, and although this does not invariably lead to NASH, the fatty liver is vulnerable to hepatocellular injury initiated by reactive oxygen species (ROS). It is critical to understand not only the triggers for hepatitis (injury and inflammation) in NASH but also how this is perpetuated as chronic liver disease. The present focus is on whether the biochemical processes that generate oxidative stress lead to hepatocyte injury and secondary recruitment of inflammation or whether inflammation is the primary mediator of liver cell injury. Insulin resistance is a reproducible pathogenic factor in NASH. It favors accumulation of free fatty acids in the liver and predisposes to oxidative stress by stimulating microsomal lipid peroxidases and by the direct effects of high insulin levels in decreasing mitochondrial beta-oxidation. CYP2E1 is normally suppressed by insulin but is invariably increased in the livers of patients with NASH. In rodent dietary models of steatohepatitis, CYP2E1 is the catalyst of microsomal lipid peroxidation, while in Cyp 2e1 nullizygous mice, CYP4A proteins are induced and function as alternative microsomal lipid peroxidases. Other studies implicate activation of peroxisome proliferator-activated receptor-alpha (PPAR alpha) as leading to NASH; PPAR alpha is a transcription factor that governs both microsomal (via CYP4A) and peroxisomal (beta-oxidation) pathways of lipid oxidation and ultimately production of ROS. Increased lipid peroxidation is a crucial difference between the livers of rodents with experimental NASH and those of ob/ob genetically obese mice that have uncomplicated steatosis. Administration of endotoxin, through the release of tumor necrosis factor-alpha (TNF-alpha), provokes liver inflammation with hepatocyte injury in the steatotic liver. This may be particularly relevant in JIB and has been suggested as a pathogenic mechanism in primary NASH. It has been proposed that inheriting one or more copies of the hemochromatosis gene, C282Y, promotes fibrotic progression in NASH because of increased hepatic iron deposition, but recent studies have failed to confirm this. The relationship between the severity of hepatitis in NASH and progression to cirrhosis implies that products of the inflammatory infiltrate play a role in fibrogenesis. In summary, NASH can be regarded as the hepatic consequence of the metabolic syndrome (or syndrome X). Attention should now shift from steatosis, a generally benign process that is less evident in the advanced stages of cirrhosis, to the mechanisms for hepatocellular injury, inflammation, and hepatic fibrosis. In particular, the genetic, molecular, and cellular factors that ordain and moderate fibrosis in the context of steatohepatitis will be of greatest relevance to effective therapy and clinical outcome.
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PMID:Etiopathogenesis of nonalcoholic steatohepatitis. 1129 94

In the past year, some relevant papers related to the diagnosis of malnutrition and its pathogenesis in cirrhosis have been published. The value of anthropometrics in the nutritional assessment of end-stage cirrhotic patients has been reinforced. Also, the role of bioelectrical impedance analysis in these patients has been redefined. Several papers have investigated the relationship between leptin and malnutrition in chronic liver disease, particularly the role of alcoholism in hyperleptinaemia, and the importance of protein-bound leptin in these patients. In other papers, the impact of both undernutrition and obesity on the outcome of liver transplantation has been investigated. Two randomized, controlled trials on enteral nutrition in liver disease have been published in this period. One of them deals with a clinical situation (i.e. severe alcoholic hepatitis) associated with a high mortality rate, whereas the second is the first controlled trial in the field of preoperative nutrition in liver transplantation. Finally, some papers provide further arguments in the dilemma of which route of nutrition (enteral or parenteral) is better in cirrhosis.
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PMID:Nutritional aspects of liver disease and transplantation. 1170 97

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that occurs in nondrinkers but which cannot be distinguished from alcohol-induced liver disease histologically. There are no diagnostic blood tests for NAFLD but the disease is associated with several insulin-resistant states, including obesity, type 2 diabetes mellitus and dyslipidemia. Most of the liver-related morbidity and mortality that accompany NAFLD occur in patients who develop cirrhosis. The latter is most likely to occur in individuals who have progressed from simple steatosis (fatty liver) to steatohepatitis, a chronic inflammatory liver lesion. The mechanisms that promote the transition from steatosis to nonalcoholic steatohepatitis appear to involve multiple cellular adaptations to the oxidative stress that occurs when fatty acid metabolism is deranged during insulin resistance. A better understanding of these mechanisms is desired to target treatments to prevent and/or reverse nonalcoholic steatohepatitis, thereby aborting the evolution of cirrhosis.
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PMID:Fat and the liver--a molecular overview. 1194 31

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that occurs in patients with no significant alcohol consumption; it is not histologically different from alcoholic hepatitis because it presents macrovesicular steatosis, hepatocellular necrosis, mixed inflammatory infiltrate, and various stages of fibrosis in addition Mallory bodies in some patients. Some authors have even described NASH as a benign disease; however, it is presently considered a potentially serious disease that may evolve into liver cirrhosis and probably, liver cancer. It is more often related to female sex, obesity, and dyslipidemia, although it may be present in other population groups and associated with other factors. Its origin may be multifactorial, including insulin resistance, protein glycation, oxidative stress, and others. The disease may be asymptomatic and found in routine physical exams when the patient shows increased aminotransferases with no other explanation. At present the only specific diagnosis procedure is liver biopsy. The sole available current treatment is body weight control, normalizing glucose and lipid blood levels, as well as the administration of some medication, as illustrated in the subsequent article.
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PMID:[Non-alcoholic steatohepatitis]. 1221 35


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