Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

More than 20% of Americans have nonalcoholic fatty liver disease (NAFLD), and this is, by far, the leading cause of abnormal liver enzymes in the United States. Nonalcoholic steatohepatitis (NASH), a more serious form of NAFLD, can proceed to cirrhosis and even hepatocellular carcinoma. These liver diseases represent the hepatic component of the metabolic syndrome, and this spectrum of liver disease represents a major health problem both in the United States and worldwide. Hepatic steatosis is closely linked to nutrition, including obesity, possibly high-fructose corn syrup consumption and consumption of certain types of fats. There are a variety of second insults or "hits" that appear to transform simple steatosis into NASH, with some of these second hits including certain proinflammatory cytokines, oxidative stress and possibly industrial toxins. In certain underdeveloped countries, it appears likely that industrial toxins play a role in NASH, and there is increasing interest in the potential interaction of industrial toxins and nutrients. Moreover, optimal therapy for NAFLD appears to include lifestyle modification with exercise, diet and weight loss. Certain nutrients may also be of benefit. Important areas for future research are the effect(s) of nutritional supplements on NAFLD/NASH and the effects of industrial toxins.
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PMID:Nonalcoholic fatty liver disease: predisposing factors and the role of nutrition. 1729 92

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

Palmitate is the most abundant saturated fatty acid in the human diet and the major one synthesized de novo. To identify palmitate-regulated genes we performed whole genome mRNA expression profiling by using human hepatoma HepG2 cells. We identified eleven genes which are significantly (single-sided permutational t-test, p<0.05) regulated by low concentration of palmitate (50 microM). We observed a decreased expression of five metallothioneins, and an increased expression of liver expressed plasminogen activator inhibitor-1 protein and insulin-like growth factor II, which play a prominent role in the development of the metabolic syndrome. Comparative promoter analysis in-silico revealed common transcriptional regulation of differentially expressed genes through erythroid kruppel-like factor and members of the zinc binding protein factor family. In conclusion, low physiological palmitate concentrations changed expression of very responsive genes.
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PMID:Identification of palmitate-regulated genes in HepG2 cells by applying microarray analysis. 1765 92

The clinicopathologic spectrum of nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Simple steatosis has a relatively benign clinical course, but NASH can progress to cirrhosis and hepatocellular carcinoma. NAFLD occurs in the absence of significant alcohol use and is considered to be the hepatic manifestation of metabolic syndrome. NAFLD affects approximately 30% of the US population and the incidence seems to be rising as the obesity epidemic continues. At present, the most accurate modality for the diagnosis of NASH is liver biopsy; however, many patients do not have a liver biopsy, and in the absence of more-accurate imaging technologies and serum markers, the diagnosis is frequently one of exclusion. As yet there is no convincingly effective treatment for NAFLD--a multimodal treatment plan that targets obesity, insulin resistance, hyperlipidemia and hypertension might be the best option for these patients.
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PMID:Evaluation and management of obesity-related nonalcoholic fatty liver disease. 1766 92

Certain selective serotonin reuptake inhibitors (SSRIs) induce the clinical and biochemical manifestations of a metabolic syndrome by as yet unknown mechanism. Here we demonstrate that incubation (1 h) of rat hepatoma Fao cells with the SSRIs paroxetine and sertraline, but not with the atypical antipsychotic drug olanzapine, inhibited the insulin-stimulated Tyr phosphorylation of the insulin receptor substrate-1 (IRS-1) with half-maximal effects at approximately 10 microM. This inhibition correlated with a rapid phosphorylation and activation of a number of Ser/Thr IRS-1 kinases including JNK, S6K1, ERK and p38 MAPK, but not PKB (Akt). JNK appears as a key player activated by SSRIs because specific JNK inhibitors partially eliminated the effects of these drugs. The SSRIs induced the phosphorylation of IRS-1 on S307 and S408, which inhibits IRS-1 function and insulin signaling. These results implicate selected SSRIs as inhibitors of insulin signaling and as potential inducers of cellular insulin resistance.
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PMID:Antidepressants induce cellular insulin resistance by activation of IRS-1 kinases. 1772 40

Nonalcoholic fatty liver disease (NAFLD) refers to the presence of hepatic steatosis not associated with a significant intake of ethanol. Insulin resistance is central to the pathogenesis of NAFLD; thus obesity, diabetes, and the metabolic syndrome are frequently associated with the disease. Consequently, as these metabolic conditions emerge as major health problems in Western society, it is now recognized that NAFLD is the most common chronic liver condition in the Western world. NAFLD is generally asymptomatic, although a minority of patients may present with evidence of progressive liver injury with complications of cirrhosis, liver failure, and hepatocellular carcinoma. Despite being common and potentially serious, relatively little is known about the natural history or prognostic significance of NAFLD. Although diabetes, obesity, and age are recognized risk factors for advanced liver disease, other significant factors leading to progressive liver injury remain to be identified. The treatment of NAFLD focuses upon modifying metabolic risk factors. Insulin-sensitizing and hepatoprotective drugs have been subjected to study trials, but as yet, no agent has conclusively been demonstrated to prevent disease progression. Management is further complicated by the inability to predict which patients will develop liver-related morbidity and thus benefit from treatment.
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PMID:Nonalcoholic fatty liver disease. 1772 49

Non-alcoholic fatty liver disease (NAFLD) is found in individuals who do not drink or abuse alcohol and represents a significant health burden for the general community. NAFLD is often associated with one or more features of the metabolic syndrome and has potential for evolution towards non-alcoholic steatohepatitis (NASH), the necro-inflammatory form of liver steatosis. The most worrisome evolutive events in a subgroup of NASH patients include advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. Pathophysiology of NAFLD/NASH is complex, but studies point to a pre-eminent role of oxidative stress and lipid peroxidation in the liver, including early mitochondrial dysfunction. Changes follow an insulin resistance status with a background of a chronic pro-inflammatory status due to an excess of visceral adiposity. Although no established therapy exists for NAFLD/NASH, potential therapeutic approaches are discussed in this review.
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PMID:Present and future therapeutic strategies in non-alcoholic fatty liver disease. 1784 48

Nine patients with hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) (six men and three women, median age 71.5 years) and one patient with intrahepatic cholangiocarcinoma (ICC), a 50-year-old man, in NASH are described. Most patients were associated with obesity, diabetes, hypertension, hypercholesterolemia, or hypertriglyceridemia. Seven patients showed insulin resistance and hyperinsulinemia. All patients except one met the criteria for metabolic syndrome. An HCC or ICC diagnosis was confirmed by tumor biopsy, surgery or autopsy except in two patients, who were diagnosed by computed tomography or hepatic angiography. The underlying liver disease was liver cirrhosis in six patients and chronic liver disease including mild hepatic fibrosis in four patients. The treatment of liver cancers consisted of surgery, radio-frequency ablation (RFA), transcatheter arterial embolization and transcatheter arterial infusion. Although the follow-up period was relatively short (median 27.5 months, average 32.1 months), all postoperative and post-RFA patients have not had a recurrence of HCC to date, except for one patient who had a palliative operation with intra-arterial infusion of anticancer drugs through an implanted reservoir port. Older age and liver cirrhosis are considered risk factors for HCC in NASH, and regular screening of these patients is necessary. Diabetes may contribute to the development of ICC in NASH. Curative therapy (surgery or RFA) and weight loss by the active therapeutic intervention (nutritional care and exercise therapy) after curative therapy may help us improve the prognosis of HCC in NASH.
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PMID:Primary liver cancers with nonalcoholic steatohepatitis. 1787 5

Many reports indicated that endocrine disruptors (EDs) affect several hormonal functions in various living things. Here, we show the effect of EDs on lipid accumulation in target cells involved in the onset of metabolic syndrome. Treatment with nonylphenol and bisphenol A, typical EDs, stimulated the accumulation of triacylglycerol in differentiated adipocytes from 3T3-L1, preadipocytes, in time- and concentration-dependent manners. Up-regulation of gene expressions involved in lipid metabolism and metabolic syndrome were observed in adipocytes treated with EDs. Similarly, stimulatory effects of EDs were also observed on the human hepatoma cell line HuH-7. These observations indicate that exposure to EDs stimulates the lipid accumulation in target cells involved in the metabolic syndrome and may cause the dysfunction of those cells, resulting in induction of metabolic syndrome.
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PMID:Life style-related diseases of the digestive system: endocrine disruptors stimulate lipid accumulation in target cells related to metabolic syndrome. 1792 41

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are gaining increasing recognition as components of the emerging epidemic of obesity in North America and in other parts of the world. These entities are considered the hepatic manifestations of the insulin resistance syndrome and represent the spectra of fatty liver disease associated with it. All features of metabolic syndrome are associated with NAFLD/NASH, including obesity, type 2 diabetes, arterial hypertension, and hyperlipidemia in the form of elevated triglyceride levels. NAFLD/NASH can progress to liver cirrhosis and has been reported as a cause of hepatocellular carcinoma. In this review, the histopathologic features of NAFLD/NASH and differential diagnostic considerations are discussed. In addition, grading and staging schema proposed and currently in use are reviewed. Finally, other aspects for consideration by practicing pathologists, such as sampling issues, histopathologic findings after therapeutic interventions, and recurrence after liver transplantation, are addressed.
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PMID:Pathology of nonalcoholic fatty liver disease. 1795 Dec 8


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