Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonalcoholic steatohepatitis (NASH) is a reasonably well-defined clinicopathological entity; it has been reported more commonly in women than in men or children of both sexes and it appears to be most closely associated with obesity, diabetes mellitus and related abnormalities, such as hyperlipidaemia and hyperglycaemia. However, the association with female gender, obesity and diabetes may not be as close as suggested by the literature and an underlying condition cannot be discerned in all cases. The natural history of the disease is poorly understood; the associated biopsy features span a wide spectrum, reaching from uncomplicated, clinically non-progressive fatty liver (not NASH in a strict sense) to a slowly progressive fatty liver with inflammation and fibrosis, to steatohepatitis with submassive hepatic necrosis, which has a subfulminant course and is often fatal. Non-progressive fatty liver appears to be very common but is of little clinical importance. The slowly progressive form of the disease represents NASH as encountered by most clinicians and pathologists. It is a common liver disease in current practice; patients may present with cirrhosis and even HCC arising from steatohepatitic cirrhosis. Subfulminant NASH has become exceedingly rare because many clinicians are now aware of the hazards of sudden weight loss, particularly in morbidly obese patients. Treatment options for NASH are still limited. The promotion of gradual weight loss in obese patients is the most widely recommended therapy but, unfortunately, this is very difficult to achieve. Avoidance of precipitous weight loss and careful control of diabetes mellitus are important and undisputed parts of patient management. Administration of UDCA as a treatment of NASH is still under study; it may be effective in some patients. The treatment of established steatohepatitic cirrhosis does not differ substantially from that of other types of cirrhosis and includes orthotopic liver transplantation.
 ...
PMID:Review: nonalcoholic steatohepatitis. 919 88

Nonalcoholic fatty liver disease (NAFLD) is very common in the United States, and in some patients it may lead to cirrhosis, liver failure, and liver cancer. NAFLD encompasses a spectrum of liver injury, ranging from steatosis to steatohepatitis, advanced fibrosis, and cirrhosis. Nonalcoholic steatohepatitis (NASH), an advanced form of NAFLD, histologically comprises steatosis, balloon degeneration, inflammation, and fibrosis in varying degrees. It is generally believed that simple steatosis is benign with minimal risk of progression, whereas NASH is progressive and can lead to cirrhosis. The commonly associated risk factors for NAFLD include obesity, hyperlipidemia, and diabetes mellitus. The pathogenesis of NAFLD and NASH is not fully known; however, current evidence suggests that insulin resistance and lipid peroxidation play a role in the pathogenesis of this condition. Currently, there are no proven effective therapies available for the treatment of NASH. Although there are numerous studies that have explored various treatments for NASH, these generally consist of small numbers of patients with suboptimal endpoints. Treatment strategies for NAFLD and NASH can be broadly divided into 1) treatment or control of underlying risk factors such as hyperlipidemia, diabetes mellitus, and obesity; and 2) specific pharmacologic therapy such as insulin sensitizers, antioxidants, or cytoprotective agents. Newer thiazolidinediones, such as rosiglitazone and pioglitazone, have shown promise in the treatment of NASH in pilot studies. However, these agents should not be used in clinical practice until their efficacy and safety are firmly established in larger studies. Despite encouraging initial studies, the recently completed multicenter, randomized, controlled trial failed to show any efficacy for ursodeoxycholic acid in the treatment of NASH. Other agents, such as vitamin E, betaine, probucol, and atorvastatin, have been explored as therapeutic agents for NASH. However, none of these studies have shown convincingly their utility in the treatment of NASH. Attempts to identify optimal therapy for patients with NASH are being vigorously pursued by the research community and important advances are expected within next several years. Until then, subjects should be advised to avoid alcohol, lose weight, and exercise regularly, and meticulous attention should be paid to the control of their risk factors such as diabetes and hyperlipidemia.
 ...
PMID:Treatment of Nonalcoholic Fatty Liver Disease. 1458 34

We analyzed lipids in liver diseases by agarose gel electrophoresis, and differential staining and simultaneous analysis of the cholesterol (Chol) and triglyceride (TG) fractions. Liver diseases were classified into chronic hepatitis (CH), liver cirrhosis (LC), hepatocellular carcinoma (HCC), and metastatic liver cancer, and each fraction was compared among these diseases. Atypical patterns that were unclassifiable according to the WHO classification of hyperlipidemia phenotypes were classified, and their clinical importance was evaluated. With progression of the pathologic conditions of CH, LC, and HCC, the T-Chol level, each Chol fraction, and the TG fraction decreased while the LDL-TG fraction increased. Metastatic liver cancer showed a lower HDL-fraction level but higher levels of the other parameters than HCC. When the subjects were classified into survivors and patients who died, the HDL fraction level in HCC and metastatic liver cancer, and the LDL level in LC and metastatic liver cancer differed between survivors and patients who died. Phenotypes of hyperlipidemia also differed among diseases, and atypical patterns were frequently observed in patients who died. There were 6 atypical patterns, of which 4 (slow alpha HDL, abnormal LDL, Lp-X, and Lp-Y) were associated with liver diseases. Slow alpha HDL appeared during slight bile stagnation and was accompanied by increases in the apo E level and the HDL particle size. Abnormal LDL appeared with severe liver dysfunction; a TG peak appeared at the position of LDL, and the HDL and VLDL fractions were negligible. Lp-X was a Chol-rich band, occurring on the cathode side of LDL in the presence of marked bile stagnation such as that in obstructive jaundice, and was accompanied by appearance of abnormal LDL. Lp-Y was similar to Lp-X in terms of mobility and associated diseases but contained Chol and TG. Abnormal LDL, Lp-X, and Lp-Y were often observed in patients with poor outcomes. Lipid analysis in liver diseases by this method showed results reflecting the pathologic conditions and may be clinically useful.
 ...
PMID:Clinical significance of abnormal lipoprotein patterns in liver diseases. 1575 28

Hypolipidemic drugs (HP drugs) are xenobiotics belonging to the peroxisome proliferator family which are used as pharmaceuticals in the treatment of human hyperlipidemia and hypercholesterolemia. They cause hepatocarcinogenesis in rodents by increasing cell proliferation. One hypothesis is that this hepatocarcinogenic effect is caused by induced oxidative stress resulting from the overproduction of reactive oxygen species (ROS) and from a decreasing antioxidant defense. In addition, ROS play a role in hepatocellular proliferation by activation of NF-kappaB and AP-1, leading to an increase in mitogenic cytokines such as tumor necrosis factor-alpha. No liver cancer incidence has been noted in individuals treated with HP drugs for brief periods of time. However, the observation that old rats and mice are more susceptible than young individuals to the hepatocarcinogenic effect caused by long term exposure to HP drugs raises the question of a potential health risk for the human population. In vitro, HP drugs cause an apoptogenic effect in human hepatocytes. This effect is related to a moderate antioxidant response, dysfunction of mitochondria caused by an overproduction of ROS and release of apoptogenic factors. Finally, the apoptogenic effect of HP drugs is observed in human hepatomas, suggesting a clinical interest of these agents in antitumoral activity.
 ...
PMID:Comparison of cytotoxicity induced by hypolipidemic drugs via reactive oxygen species in human and rodent liver cells. 1607 59

Nonalcoholic fatty liver disease (NAFLD) is becoming an increasing cause of chronic liver damage. The decision of start a medical treatment is based on the documented risk of progression to cirrhosis and liver cancer, when steatohepatitis (NASH) occurs. The therapy of this syndrome requires, as obviously, some considerations on the natural history of the condition, on the efficacy and safety of various therapeutic options, as well as on the costs. Treatment of patients with NAFLD has typically been focused on the management of associated conditions such as obesity, diabetes mellitus and hyperlipemia. Weight loss improves insulin sensitivity, and NASH may resolve with weight reduction. Insulin resistance seems to be the common denominator in many cases of NAFLD. Two classes of drugs have been shown to correct insulin resistance: biguanides (e.g., metformin) and thiazolidinediones (e.g., rosiglitazone and pioglitazone). The last two decades have witnessed a considerable progress in the understanding of the mechanisms respon-sible for the fibrogenic progression of chronic liver diseases. Several drugs believed to be hepatoprotective or antifibrotic agent as UDCA, betaine, vitamin E, lecithin, beta-carotene and selenium have been used in patients with NASH. Silybin is the main component of silymarin that is absorbed when linked whith a phytosome. This substance reduces in rats the lipid-peroxidation and the activaction of hepatic stellate cells. In humans, some non controlled data show that silybin is able to reduce insulin resistance, liver steatosis and plasma markers of liver fibrosis.
 ...
PMID:The treatment of NAFLD. 1623 94

Non-alcoholic steatohepatitis (NASH), the metabolic syndrome of the liver, characterised by the consequences of obesity (insulin resistance, production of free radicals, chronic inflammation) has become a new epidemic in the United States as in Europe. Diagnosis is suspected in patients with obesity, denying alcohol abuse, having typical co-morbitities (Hypertension, Diabetes mellitus, Hyperlipidemia). Liver histology confirms the diagnosis of NASH. Fatty liver without inflammation bears a good prognosis. Liver fibrosis, however, in NASH patients signalizes progression to liver cirrhosis and even HCC. Treatment modalities are limited. Reduction of body weight, physical activity, treatment of co-morbitities, specially Hypertension and Diabetes are of paramount importance. At the moment it remains unclear whether glitazone treatment could be introduced in the therapeutic armentarium.
 ...
PMID:[Non-alcoholic steatohepatitis--a new epidemic]. 1806 58

Silymarin is a naturally available bioflavonoid and is a strong antioxidant with a capacity to inhibit the formation of tumors in several cancer models. In the present study, we investigated whether dietary supplementation of silymarin has any role in lipid components, lipid-metabolizing enzymes, free fatty acid profile, and expression of cyclooxygenase-2 (COX-2) in N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma in rats. NDEA-induced rats showed severe hyperlipidemia along with upregulated expression of COX-2 as revealed by western blotting and immunohistochemistry. Dietary silymarin supplementation attenuated this hyperlipidemia and downregulated the expression of COX-2. Thus we conclude that compounds like silymarin with potent hypolipidemic effect are strong candidates as chemopreventive agents for the treatment of liver cancer.
 ...
PMID:Silymarin downregulates COX-2 expression and attenuates hyperlipidemia during NDEA-induced rat hepatocellular carcinoma. 1837 78

This article reviews evidence that causally links hormonal disorders with hepatobiliary disease, and gives particular focus to nonalcoholic steatohepatitis (NASH). The downstream mechanisms by which endocrine disturbances cause liver disease might be similar to those involved in the development of primary liver disease. Hypothyroidism, for example, might lead to NASH, cirrhosis and potentially liver cancer via the development of hyperlipidemia and obesity. Patients with growth hormone deficiency have a metabolic-syndrome-like phenotype that is also associated with the development of NASH. Polycystic ovary syndrome is a common endocrine disorder that is often associated with insulin resistance, the metabolic syndrome, altered levels of liver enzymes and the development of NASH. Recent findings support a role of dehydroepiandrosterone sulfate deficiency in the development of advanced NASH. In addition, adrenal failure is increasingly reported in patients with end stage liver disease and in patients who have received a liver transplant, which suggests a bidirectional relationship between liver and endocrine functions. Clinicians should, therefore, be aware of the potential role of endocrine disorders in patients with cryptogenic liver disease and of the effects of liver function on the endocrine system.
 ...
PMID:Endocrine and liver interaction: the role of endocrine pathways in NASH. 1934 15

In explant livers with chronic hepatitis C (HCV-C) we have noted a distinctive histologic variant that we have termed steatohepatitic hepatocellular carcinoma (SH-HCC) with features resembling non-neoplastic steatohepatitis, including large droplet steatosis, ballooning of malignant hepatocytes, Mallory-Denk bodies, inflammation, and pericellular fibrosis. This study was undertaken to further describe the characteristics and prevalence of this histologic variant in HCV-C and any possible association with underlying risk factors for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). We selected two 2-year periods (mid-2003 to mid-2005 and 2007 to 2008), from which selected explant livers with HCV-C and HCC were examined to determine the characteristics and frequency of SH-HCC. The underlying cirrhotic liver was also reassessed for steatosis and evidence of steatohepatitis. Clinical records were consulted for concomitant NAFLD and NASH risk factors. The SH-HCC variant was found in a total of 22 of 62 HCC cases (35.5%). Fourteen of the 22 patients with SH-HCC (63.6%) had at least one known risk factor for NAFLD/NASH including diabetes (6 of 22, 27.3%), obesity (6 of 22, 27.3%), hypertension (11 of 22, 50%), and hyperlipidemia (5 of 22, 27.8%). In 14 of the 22 cases (63.6%) of SH-HCC, the non-neoplastic liver showed changes of NAFLD/NASH superimposed on otherwise typical features of HCV-C. In conclusion, in our series of HCV-C explants, approximately one-third of HCCs show a distinctive histological variant termed SH-HCC. Underlying risk factors for NAFLD and for NASH were identified in 63.6% of our cases. Moreover, non-neoplastic tissue in HCV-C explants showed changes of NAFLD/NASH in 63.6% of cases. These results suggest a possible NAFLD/NASH pathway leading to SH-HCC in the setting of HCV-C which requires further investigation in the future.
 ...
PMID:Steatohepatitic hepatocellular carcinoma (SH-HCC): a distinctive histological variant of HCC in hepatitis C virus-related cirrhosis with associated NAFLD/NASH. 2097 41

Non-alcoholic fatty liver disease (NAFLD) is the most common and emerging form of chronic liver disease worldwide. It includes a wide spectrum of liver diseases ranging from simple fatty liver to steatohepatitis, which may progress to cirrhosis, liver cancer, and liver mortality. Common metabolic diseases, which are well established cardiovascular risk factors, have been associated to NAFLD and cardiovascular disease is the single most important cause of morbidity and mortality in this patient population. The pathogenesis of NAFLD appears multifactorial and many mechanisms have been proposed as possible causes of fatty liver infiltration. Management of fatty liver has become a major challenge to healthcare systems as the consequence of the increasing rates of obesity worldwide. First-line management focuses on lifestyle modifications. Moderate weight reduction either by dietary restriction or by increased habitual physical activity is safe and highly recommended. Several therapeutic interventions have been proposed. These include insulin sensitizer agents, lipid lowering drugs, antioxidants such as vitamin E and supplementation of vitamin D3. However, therapeutic strategies have been largely empirical so far, and experimental trials have mostly been carried out in uncontrolled settings with small sample sizes. Metabolic conditions such as diabetes mellitus, obesity, hypertension and hyperlipidemia, should be strongly considered and a multidisciplinary approach should be personalized for individual patients. Treatment of co-morbidities should be regarded as of paramount importance in the management of these patients. The purpose of this review is to examine different approaches for the clinical management of non-alcoholic fatty liver disease.
 ...
PMID:Modern approach to the clinical management of non-alcoholic fatty liver disease. 2502 93


1 2 Next >>