Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Non-alcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) is a well-established cause for chronic liver disease. In most studies on NASH, elevation in alanine aminotransferase (ALT) is taken as one of the diagnostic criteria. However, the clinical and histological spectrum and natural history of NAFLD with normal ALT are not well explored. This study was planned to define the clinical spectrum and natural history of patients with NAFLD with normal ALT, and to compare them with NAFLD with abnormal ALT. A prospective study including 81 consecutive patients with ahistological diagnosis ofNAFLD was planned during the period from 1999 to 2003. Consecutive (n=81) patients with the histological diagnosis of NAFLD were included in the study. In all the patients, clinical, anthropometric, laboratory, histological and imaging features were noted at the baseline. All these patients were followed up regularly at 6-month intervals. Of the 81 cases, 25 patients (including 60% cirrhotics) had persistently normal enzyme, whereas 56 (including 23% cirrhotics) had abnormal ALT. Both the groups were comparable with respect to distribution of age, gender, ethnicity, clinical features, imaging features, histological severity and laboratory features; except a higher incidence of diabetes and higher occurrence of advanced liver disease at baseline in NAFLD with normal ALT. Natural history of NAFLD was better in patients without cirrhosis irrespective of baseline ALT levels than in patients with cirrhosis; except for a higher incidence of decompensation in cirrhotics with normal ALT. The entire clinical and histological spectrum of NAFLD is seen in patients with normal ALT and is not different from patients with abnormal ALT. In patients with diabetes and hepatomegaly in the absence of other obvious liver diseases, even normal ALT may not rule out advanced liver disease, and liver biopsy may be necessary to identify the severity of liver disease.
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PMID:Clinical spectrum and natural history of non-alcoholic steatohepatitis with normal alanine aminotransferase values. 1568 60

Non-alcoholic steatohepatitis (NASH) represents only a part of a wide spectrum of non-alcoholic fatty liver disease (NAFLD) and its prevalence is only 2 - 3% in the general population. Obesity, diabetes, hyperlipidemia and female sex are important risk factors for NASH. Two hit theory describes very well the pathogenesis of NASH wherein hepatic steatosis, the first hit is followed up by the second hit, one of which may be reactive oxygen species. Mitochondria is the main source of reactive oxygen species which may trigger steatohepatitis by lipid peroxidation, cytokine induction or induction of fas-ligand. Insulin resistance syndrome is the only metabolic syndrome that has been consistently associated with NASH. The diagnosis rests on the hallmark histological features and rigorous exclusion of significant alcohol consumption. Most patients are asymptomatic, have mild-to-moderate elevations of serum aminotransferase levels, clinical hepatomegaly and features of fatty liver on imaging. Liver biopsy is essential for positive diagnosis and prognostication of NASH. Histologically, fat deposition is typically macrovesicular and inflammation of steatohepatitis is predominantly lobular. Neutrophilic cells in lobular inflammatory infilterate are a distinguishing feature of steatohepatitis and differentiate it from other chronic hepatitis. The pattern of collagen deposition is perivenular & peri-sinusoidal spaces in zone 3. NASH is a progressive disease in more than one in four and has spontaneous regression in less than one in six. Therapy options include weight reduction in obese, good control in diabetics and exercise. Ursodeoxycholic acid has membrane stabilizing, cytoprotective and immunological effect and normalizes raised transaminases. Liver transplantation has been done in NASH but transplanted liver shows re-development in more than two thirds. Many more therapies are in the pipeline and show promise for the future.
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PMID:Non-alcoholic steatohepatitis. 1592 3

Non-alcoholic steatohepatitis (NASH) is one of the most common liver disorders. This is highly prevalent in obese and diabetic subjects. Persons with central obesity are at particular risk. Other clinical predictors are age more than 40-50 years and hyperlipidemias, but none of these factors is invariable for causation of NASH. Other reported associations are, celiac disease, Wilson's Disease and few other metabolic diseases. Drugs, particularly amiodarone, tamoxifen, nucleoside analogues and methotrxate have also been linked to NASH. The disease is evenly distributed in both sexes but advanced disease is more common in women. Ethnic variation exists and African Americans are less affected than Hispanic Americans. Specific clinical features of NASH are infrequent. Patients usually come to clinical attention by elevated liver enzymes found on routine evaluation but on history, about two third of patients will admit to have mild fatigue and about half will report right upper quadrant pain. Rarely, patient may present with a complication of cirrhosis. Physical examination may reveal hepatomegaly and splenomegaly. Research in last few years has stressed that development of steatosis, stetohepatitis, fibrosis with subsequent cirrhosis are most probably the result of insulin resistance. Therefore, clinical features may reflect existence of insulin resistance. Obesity, particularly central obesity is most important of these. Patients may have sleep apnea syndrome. Hypertension and manifestations of diabetes mellitus like polyuria, polydypsia, and neurological deficits may occur. Patients may have varying combination of obesity, diabetes, hyperlipidemia, hypertension and impaired fibrinolysis (syndrome X). Children with insulin resistance may show acanthosis nigricance. Patients with polycystic ovary syndrome, which consists of insulin resistance, diabetes, obesity, hirsutism, oligo or polymenorrha and hyperlipidemia may have NASH. Other rare manifestations of insulin resistance, which can be seen in patients of NASH are lipomatosis, lipoatrophy/lipodystrophy and panniculitis. Most other rare conditions known to cause NASH like peroxisomal diseases, mitochondialpathies, Weber-Christian disease, Mauriac syndrome, Madelung's lipomatosis and abetaliopprotenemia also have insulin resistance. This is believed that primary defect underlying insulin resistance is impairment in postreceptor pathways (through tyrosine kinase activity) of insulin action. Primary defect in insulin receptors appear uncommon. This results in down regulation of insulin receptor substance 1 (IRS-1) signaling by excess free fatty acids. In muscle, activated IRS-1 promotes translocation of glucose transporter protein 4 (GLUT4) to cell membrane. As a result, monocyte glucose uptake by GLUT4 increases glucose disposal from blood and reduced need for insulin. PKC-0 is a likely candidate as serine kinase in muscle regulated by fatty acids that can impair the activation of IRS-1. Insulin resistance is usually evaluated by fasting insulin levels, Quantitative Insulin Check Index (QUICKI) and Homeostasis Model Assessment of Insulin Resistance (HOMA), C-peptid/insulin ratio oral glucose tolerance test and hyper insulinemic euglycemic clamp. The clamp technique is considered the gold standard.
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PMID:Insulin resistance and clinical aspects of non-alcoholic steatohepatitis (NASH). 1619 20

Non-alcoholic fatty liver disease (NAFLD) is common in obesity. However, weight reduction alone does not prevent the progression of NAFLD to end-stage disease associated with the development of cirrhosis and liver disease. In a previous experiment, 50% ethanol extract of Acanthopanax senticosus stem bark (ASSB) was found to reduce body weight and insulin resistance in high fat diet-induced hyperglycemic and hyperlipidemic ICR mice. To evaluate the anti-steatosis action of ASSB, insulin-resistant ob/ob mice with fatty livers were treated with ASSB ethanol extract for an 8 week-period. ASSB ethanol extract reversed the hepatomegaly, as evident in reduction of % liver weight/body weight ratio. ASSB ethanol extract also specifically lowered circulating glucose and lipids, and enhanced insulin action in the liver. These changes culminated in inhibition of triglyceride synthesis in non-adipose tissues including liver and skeletal muscle. Gene expression studies confirmed reductions in glucose 6-phosphatase and lipogenic enzymes in the liver. These results demonstrate that ASSB ethanol extract is an effective treatment for insulin resistance and hepatic steatosis in ob/ob mice by decreasing hepatic lipid synthesis.
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PMID:Acanthopanax senticosus reverses fatty liver disease and hyperglycemia in ob/ob mice. 1702 51

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. It encompasses a wide spectrum of liver lesions, from pure steatosis to end-stage liver disease with cirrhosis and hepatocellular carcinoma. Nonalcoholic steatohepatitis corresponds only to one stage of NAFLD. As NAFLD can be considered a liver manifestation of the metabolic syndrome, its prevalence is high in obese people and in patients who have type 2 diabetes-insulin resistance is one of the key elements of the pathogenesis of NAFLD. This disease is often asymptomatic in the absence of decompensated cirrhosis, but should be suspected in patients with elevated aminotransferase levels or radiological evidence of a fatty liver or hepatomegaly. Liver fibrosis is associated with age over 50 years, obesity, diabetes and high triglyceride levels. Liver biopsy is the only way to assess the histologic features of necrotic inflammation and fibrosis that define nonalcoholic steatohepatitis and to determine its probable prognosis. The prognosis is good for pure steatosis, whereas the presence of necrotic inflammation is associated with a significant risk of progression to cirrhosis and, possibly, hepatocellular carcinoma. Lifestyle changes, such as dietary modifications and exercise, are recommended. To date, there have been very few randomized, placebo-controlled trials of drug treatments for NAFLD.
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PMID:Nonalcoholic fatty liver disease: from pathogenesis to patient care. 1751 90

Non-alcoholic steatohepatitis (NASH) is a term used to describe a spectrum of conditions characterized by histological findings of hepatic macrovesicular steatosis with inflammation in individuals who consume little or no alcohol. The NASH patients progress to liver cirrhosis and even hepatocellular carcinoma (HCC). Hepatocyte-specific phosphatase and tensin homolog (PTEN)-deficient mice (PTEN-deficient mice), which the authors had generated previously, showed massive hepatomegaly and steatohepatitis with triglyceride accumulation followed by liver fibrosis and HCC, a phenotype similar to human NASH. Therefore, it was shown that PTEN deficiency in hepatocytes could induce hepatic steatosis, inflammation, fibrosis and tumors and that PTEN-deficient mice were a useful animal model for not only the understanding of the pathogenesis of NASH but also the development of treatment for NASH.
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PMID:Non-alcoholic steatohepatitis and hepatocellular carcinoma: lessons from hepatocyte-specific phosphatase and tensin homolog (PTEN)-deficient mice. 1756 78

Recent studies have shown that dietary phospholipids, especially phosphatidylcholine and phosphatidylserine, have various beneficial biological effects. However, there are not enough data concerning the physiological function of dietary phosphatidylinositol (PI). The metabolic syndrome, a cluster of metabolic abnormalities such as dyslipidemia, diabetes mellitus, and hypertension, is a widespread and increasingly prevalent disease in industrialized countries. Nonalcoholic fatty liver disease (NAFLD) is often associated with features of the metabolic syndrome. NAFLD describes 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 worldwide. The present study examined whether dietary PI protects Zucker ( fa/ fa) rats from the metabolic syndrome. For 4 weeks, rats were fed semisynthetic diets containing either 7% soybean oil or 5% soybean oil plus 2% PI. Dietary PI markedly prevented the development of hepatomegaly and hepatic steatosis and lowered hepatic injury markers in serum. Additionally, hyperinsulinemia was relieved by the feeding of dietary PI in Zucker rats. These effects were attributable to an increase in serum adiponectin, enhancement of fatty acid beta-oxidation, and suppression of mRNA expression of inflammatory genes in the liver. This is the first report that dietary PI increases serum adiponectin level and prevents the development of NAFLD in a rat model of the metabolic syndrome.
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PMID:Dietary phosphatidylinositol prevents the development of nonalcoholic fatty liver disease in Zucker (fa/fa) rats. 1832 72

Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology--from steatosis alone, through the necroinflammatory disorder of non-alcoholic steatohepatitis (NASH) to cirrhosis and liver cancer. NAFLD/NASH is mostly related with visceral adiposity, obesity, type 2 diabetes melitus (DM t.2) and metabolic syndrome. Pathogenetic concepts of NAFLD include overnutrition and underactivity, insulin resistance (IR) and genetic factor. The prevalence of NAFLD has been estimated to be 17-33% in some countries, NASH may be present in about 1/3 of such cases, while 20-25% of NASH cases could progress to cirrhosis. NAFLD is now recognized as one of the most frequent reason of liver tests elevation without clinical symptoms. Insulin resistance is considering as having a central role in NAFLD pathogenesis. In hepatocytes, IR is related to hyperglycaemia and hyperinsulinaemia, formation of advanced glycation end-products, increased free fatty acids and their metabolites, oxidative stress and altered profiles of adipocytokines. Early stages of fatty liver are clinically silent and include elevation of ALT and GGTP, hyperechogenic liver in USG and/or hepatomegaly. Among clinical symptoms, abdominal discomfort is relatively common as well as chronic fatigue. NAFLD/NASH is not a benign disease, progressive liver biopsy have shown histological progression of fibrosis in 32%, the estimated rate of cirrhosis development is 20% and a liver--related death is 12% over 10 years. No treatment has scientifically proved to ameliorate NAFLD or to avoid its progression. The various therapeutic alternatives are aimed at interfering with the risk factors involved in the pathogenesis of the disorder in order to prevent the progression to end-stage liver disease. The most important therapeutic measure is increasing insulin sensitivity by an attempt to change a lifestyle mostly by dieting and physical activity in order to loose weight. The most used agent is metformin, the others are under controlled trials or their effectiveness is low. NASH is not a common indication for liver transplantation because of the older age distribution of patients and high prevalence of comorbidity, related to metabolic syndrome. Recurence of NASH in the grafted liver is also a relatively frequent complication.
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PMID:[Non-alcoholic fatty liver disease--new view]. 1870 46

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. Thus, the discovery of food components that would ameliorate NAFLD is of interest. Various mushrooms have been used in folk medicine for the treatment of lifestyle diseases in eastern countries and several compounds that modulate immune system, lower blood lipid levels, inhibit tumor and viral action have been isolated from them. In this study, we tested whether feeding Panellus serotinus (Mukitake) to db/db mice protects them from hepatic injury. After 4 weeks of feeding, hepatomegaly, hepatic triglyceride accumulation and elevated hepatic injury markers in serum were markedly alleviated in Mukitake-fed db/db mice compared with control mice. These effects were partly attributable to the enhancement of lipolytic enzyme activity and the suppression of lipogenic enzyme activities due to the Mukitake diet. The severe hyperinsulinemia in control db/db mice tended to attenuate in Mukitake-fed mice due to an enhanced production of adiponectin, which improves insulin sensitivity. Moreover, production of monocyte chemoattractant protein 1 (MCP1), an inflammatory cytokine, was markedly suppressed by the Mukitake diet. In addition, water-soluble extracts of Mukitake powder showed an inhibitory effect on inhibitor of kappaB (IkappaB) kinase (IKK) beta, whose activation is required for nuclear factor kappaB (NFkappaB)-mediated inflammatory response. We speculate that the development and progression of NAFLD was prevented by the reduction of MCP1 production through the interference in the IKKbeta-NFkappaB signaling pathway in Mukitake-fed db/db mice.
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PMID:Mukitake mushroom (Panellus serotinus) alleviates nonalcoholic fatty liver disease through the suppression of monocyte chemoattractant protein 1 production in db/db mice. 1942 19


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