Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-alcoholic fatty liver disease represents a set of liver lesions similar to those induced by alcohol that develop in individuals with no alcohol abuse. When lesions consist of fatty and hydropic degeneration, inflammation, and eventually fibrosis, the condition is designated non-alcoholic steatohepatitis (NASH). The pathogenesis of these lesions is not clearly understood, but they are associated with insulin resistance in most cases. As a result, abdominal fat tissue lipolysis and excessive fatty acid uptake by the liver occur. This, together with a disturbance of triglyceride export as VLDL, results in fatty liver development. Both the inflammatory and hepatocellular degenerative components of NASH are attributed to oxidative stress. Mitochondrial respiratory chain loss of activity plays a critical role in the genesis of latter stress. This may be initiated by an increase in the hepatic TNFalpha, iNOS induction, peroxynitrite formation, tyrosine nitration and inactivation of enzymes making up this chain. Consequences of oxidative stress include: lipid peroxidation in cell membranes, stellate cell activation in the liver, liver fibrosis, chronic inflammation, and apoptosis.
 ...
PMID:Non-alcoholic fatty liver disease. From insulin resistance to mitochondrial dysfunction. 1719 77

Although the vast majority of heavy drinkers and individuals with obesity, insulin resistance, and the metabolic syndrome have steatosis, only a minority ever develop steatohepatitis, fibrosis, and cirrhosis. Genetic and environmental risk factors for advanced alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) seem likely to include factors that influence the severity of steatosis and oxidative stress, the cytokine milieu, the magnitude of the immune response, and/or the severity of liver fibrosis. For ALD, the dose and pattern of alcohol intake, coffee intake, and dietary and other lifestyle factors leading to obesity are the most important environmental determinants of disease risk. For NAFLD, dietary saturated fat and antioxidant intake, small bowel bacterial overgrowth, and obstructive sleep apnea syndrome may play a role. Family studies and interethnic variations in susceptibility suggest that genetic factors are important in determining disease risk. For ALD, functional polymorphisms in the ADH and ALDH alcohol metabolizing genes play a role in determining susceptibility in Oriental populations. No genetic associations with advanced NAFLD have been replicated in large studies. Preliminary data suggest that polymorphisms in the genes encoding microsomal triglyceride transfer protein, superoxide dismutase 2, the CD14 endotoxin receptor, tumor necrosis factor alpha, transforming growth factor beta, and angiotensinogen may be associated with steatohepatitis or hepatic fibrosis or both.
 ...
PMID:Genetics of alcoholic liver disease and nonalcoholic fatty liver disease. 1729 76

The term "non-alcoholic fatty liver disease" (NAFLD) encompasses a wide range of pathological conditions ranging from accumulation of fat (fatty liver) to various degrees of inflammation and fibrosis (NASH), and finally to cryptogenic cirrhosis and its clinical sequelae (HCC, liver decompensation). The progression from one stage to the next can be triggered by genetic and environmental factors alone and also through their interaction. Fatty liver is known to follow a benign course, whereas the presence of inflammation, ballooning degeneration, and fibrosis, which are typical features of NASH, can lead to cirrhosis. Despite the serious risks associated with NASH, there are few tools for monitoring the progression of the disease and identification of high-risk patients. The aim of this article is to review the pros and cons of some noninvasive methods for assessing liver fibrosis in NASH.
 ...
PMID:Noninvasive assessment of fibrosis in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). 1732 Jul 97

Oxidative stress leads to chronic liver damage. Silybin has been conjugated with vitamin E and phospholipids to improve its antioxidant activity. Eighty-five patients were divided into 2 groups: those affected by nonalcoholic fatty liver disease (group A) and those with HCV-related chronic hepatitis associated with nonalcoholic fatty liver disease (group B), nonresponders to treatment. The treatment consisted of silybin/vitamin E/phospholipids. After treatment, group A showed a significant reduction in ultrasonographic scores for liver steatosis. Liver enzyme levels, hyperinsulinemia, and indexes of liver fibrosis showed an improvement in treated individuals. A significant correlation among indexes of fibrosis, body mass index, insulinemia, plasma levels of transforming growth factor-beta, tumor necrosis factor-alpha, degree of steatosis, and gamma-glutamyl transpeptidase was observed. Our data suggest that silybin conjugated with vitamin E and phospholipids could be used as a complementary approach to the treatment of patients with chronic liver damage.
 ...
PMID:The effect of a silybin-vitamin e-phospholipid complex on nonalcoholic fatty liver disease: a pilot study. 1741 Apr 54

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.
 ...
PMID:Nonalcoholic fatty liver disease: from pathogenesis to patient care. 1751 90

The aim of this study was to investigate the protective effect of breviscapine extracted from the Chinese herb Erigeron breviscapus on liver injury in diabetic rats induced by streptozotocin. Treatment with breviscapine significantly reduced liver weight, liver lipid level, fatty liver and liver fibrosis score in diabetic rats. Treatment with breviscapine also significantly decreased lipid peroxidation malondiadehyde levels and increased the activities of antioxidative enzymes such as superoxide dismutase, catalase and glutathione peroxidase in diabetic liver. Immunohistochemical observations revealed that macrophage (ED-1-positive cells) infiltration in diabetic liver was inhibited by treatment with breviscapine. Western blot analysis showed that the expression of transforming growth factor-beta1 in diabetic liver was lowered by breviscapine treatment. In conclusion, our results indicate that breviscapine has potential as a treatment for diabetic liver injury through attenuating liver lipid accumulation and oxidative stress.
 ...
PMID:Prevention of early liver injury by breviscapine in streptozotocin-induced diabetic rats. 1756 45

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.
 ...
PMID:Non-alcoholic steatohepatitis and hepatocellular carcinoma: lessons from hepatocyte-specific phosphatase and tensin homolog (PTEN)-deficient mice. 1756 78

Liver fibrosis results from chronic damage to the liver in conjunction with the progressive accumulation of fibrillar extracellular matrix proteins. Fibrosis progression in patients with chronic viral hepatitis is a dynamic process where hepatic stellate cells, the most important contributor cell type, respond to a variety of host genetic factors and viral proteins. The abuse of alcohol, superimposed fatty liver disease, and age at the time of viral infection are some of the factors that accelerate liver fibrosis. Liver biopsy remains the gold standard to diagnose fibrosis and significant advances have been made to develop noninvasive markers for liver fibrosis.
 ...
PMID:Liver fibrosis and chronic viral hepatitis. 1761 56

Liver fibrosis may be considered as a dynamic and integrated cellular response to chronic liver injury. The activation of hepatic stellate cells and the consequent deposition of large amounts of extracellular matrix play a major role in the fibrogenic process, but it has been shown that other cellular components of the liver are also involved. Although the pathogenesis of liver damage usually depends on the underlying disease, oxidative damage of biologically relevant molecules might represent a common link between different forms of chronic liver injury and hepatic fibrosis. In fact, oxidative stress-related molecules may act as mediators able to modulate all the events involved in the progression of liver fibrosis. In addition, chronic liver diseases are often associated with decreased antioxidant defenses. Although vitamin E levels have been shown to be decreased in chronic liver diseases of different etiology, the role of vitamin E supplementation in these clinical conditions is still controversial. In fact, the increased serum levels of alpha-tocopherol following vitamin E supplementation not always result in a protective effect on liver damage. In addition, clinical trials have usually been performed in small cohorts of patients, thus making definitive conclusions impossible. At present, treatment with vitamin E or other antioxidant compounds could be proposed for nonalcoholic fatty liver disease (NAFLD), the most frequent hepatic lesion in western countries which can progress to nonalcoholic steatohepatitis and cirrhosis due to the production of large amounts of oxidative stress products. However, although some studies have shown encouraging results, multicentric and long-term clinical trials are needed.
 ...
PMID:Vitamin E in chronic liver diseases and liver fibrosis. 1762 89

Liver steatosis, diabetes mellitus and hepatitis C virus (HCV) genotype have been implicated in liver fibrosis in HCV-related chronic active hepatitis (CAH). The aim of this study was to evaluate whether steatosis and diabetes were associated with more severe liver fibrosis in patients with genotype 1b HCV-related CAH. One-hundred and eighty patients (98 men, 82 women; age range 17-68 years; median 51) infected with genotype 1b HCV underwent ultrasound examination and liver biopsy because of elevated levels of serum alanine transaminase. Based on liver histology, patients were divided into three steatosis classes: 1 (involving <33% of hepatocytes), 2 (34-66%) and 3 (>66%). Fibrosis was graded with the Ishak score (range: 0-6). Virological and epidemiologic characteristics, biochemical data, body mass index, and apparent duration of disease were recorded. Diabetes was identified according to American Diabetes Association criteria. The median fibrosis grade was 2 (23 patients had liver cirrhosis) in the three steatosis classes, with no significant differences between classes. At multivariate analysis, fibrosis was significantly related to age, alanine transaminase, diabetes, hepatitis B core antibody, steatohepatitis and grading. At binary logistic regression analysis, only diabetes and fibrosis stage were significantly associated with steatohepatitis. Steatosis was not an independent risk factor for liver disease severity in our CAH/genotype 1b HCV-infected patients. Steatohepatitis was associated as well as diabetes and affected the severity of liver fibrosis.
 ...
PMID:Steatohepatitis is associated with diabetes and fibrosis in genotype 1b HCV-related chronic liver disease. 1787 6


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>