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)

Liver cirrhosis is the end-stage of chronic liver disease. Even at the compensated stage complications are multiple, severe and potentially fatal which are related to liver insufficiency, portal hypertension and a pre-cancerous stage. It is now possible to diagnose cirrhosis through non invasive tools like biochemical scores and Fibroscan. It may be reversible provided adequate counselling about excessive alcohol intake and metabolic syndrome and specific treatments such as antivirals, venesection, immunosuppressive therapies are implemented. The role of the general practitioner is to diagnosis and treat cirrhosis early together with the hepatogastroenterologist. He can also, through simple means, prevent complications such as hepatocellular carcinoma, variceal bleeding, overt encephalopathy and renal failure and liver decompensation after surgery.
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PMID:[How to prevent complications of liver cirrhosis?]. 1795 20

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.
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PMID:[Non-alcoholic steatohepatitis--a new epidemic]. 1806 58

Nonalcoholic fatty liver disease (NAFLD) includes hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. NAFLD is the most common liver disorder in the United States and worldwide. Due to the rapid rise of the metabolic syndrome, the prevalence of NAFLD has recently dramatically increased and will continue to increase. NAFLD has also the potential to progress to hepatocellular carcinoma (HCC) or liver failure. NAFLD is strongly linked to caloric overconsumption, physical inactivity, insulin resistance and genetic factors. Although significant progress in understanding the pathogenesis of NAFLD has been achieved in years, the primary metabolic abnormalities leading to lipid accumulation within hepatocytes has remained poorly understood. Mitochondria are critical metabolic organelles serving as "cellular power plants". Accumulating evidence indicate that hepatic mitochondrial dysfunction is crucial to the pathogenesis of NAFLD. This review is focused on the significant role of mitochondria in the development of NAFLD.
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PMID:Nonalcoholic fatty liver disease and mitochondrial dysfunction. 1818 54

Chronic exposure to glucocorticoid hormones, resulting from either drug treatment or Cushing's syndrome, results in insulin resistance, central obesity, and symptoms similar to the metabolic syndrome. We hypothesized that the major metabolic effects of corticosteroids are mediated by changes in the key metabolic enzyme adenosine monophosphate-activated protein kinase (AMPK) activity. Activation of AMPK is known to stimulate appetite in the hypothalamus and stimulate catabolic processes in the periphery. We assessed AMPK activity and the expression of several metabolic enzymes in the hypothalamus, liver, adipose tissue, and heart of a rat glucocorticoid-excess model as well as in in vitro studies using primary human adipose and primary rat hypothalamic cell cultures, and a human hepatoma cell line treated with dexamethasone and metformin. Glucocorticoid treatment inhibited AMPK activity in rat adipose tissue and heart, while stimulating it in the liver and hypothalamus. Similar data were observed in vitro in the primary adipose and hypothalamic cells and in the liver cell line. Metformin, a known AMPK regulator, prevented the corticosteroid-induced effects on AMPK in human adipocytes and rat hypothalamic neurons. Our data suggest that glucocorticoid-induced changes in AMPK constitute a novel mechanism that could explain the increase in appetite, the deposition of lipids in visceral adipose and hepatic tissue, as well as the cardiac changes that are all characteristic of glucocorticoid excess. Our data suggest that metformin treatment could be effective in preventing the metabolic complications of chronic glucocorticoid excess.
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PMID:AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushing's syndrome. 1819 20

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the United States secondary to the growing obesity epidemic. Although most patients with NAFLD do not develop progressive liver disease, the subset of NAFLD patients with nonalcoholic steatohepatitis (NASH) are at risk for progression to cirrhosis and hepatocellular carcinoma, which necessitates appropriate follow-up and management. Unfortunately, proven treatment modalities for NASH that result in complete histopathologic regression of steatosis, inflammation, and fibrosis do not exist. Many therapeutic approaches to NAFLD management have been attempted, with varying degrees of success. However, most of these studies have been limited to small, single-center, uncontrolled trials. Based on our evolving understanding of the disease's pathogenesis, it seems logical that a multidisciplinary approach addressing the underlying metabolic syndrome and the resultant intrinsic liver injury is necessary. Diet, exercise, surgical weight loss, diabetic medications, and hepatoprotective agents all have been studied and may serve as potential weapons in our armamentarium against this disease. Although most of these approaches have been studied as single-modality therapy, we believe that combination, multimodality therapy is required to treat this disease effectively.
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PMID:Current treatments in nonalcoholic steatohepatitis. 1822 3

Although not associated with the metabolic syndrome, HCV is linked with impaired insulin signalling, insulin resistance, hypocholesterolemia and steatosis which represent a distinct HCV-associated dysmetabolic syndrome. Insulin resistance affects the development of diabetes, fibrosis, impaired response to antivirals and perhaps hepatocellular carcinoma risk. HCV infection is associated with hypocholesterolemia and steatosis reversible after sustained virologic response. A "viral", and a "metabolic" steatosis exist as function of viral genotypes. Little is known about the possible role of HCV in further components of the metabolic syndrome such as atherosclerosis, obesity, arterial hypertension, hyperuricemia and thrombotic risk factors.
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PMID:Dysmetabolic changes associated with HCV: a distinct syndrome? 1827 9

Non-alcoholic fatty liver disease (NAFLD) is now the commonest liver disorder in the developed world affecting up to a third of individuals. It is closely associated with features of the metabolic syndrome, particularly obesity and diabetes. It can progress to cirrhosis, hepatocellular carcinoma and liver failure and is an increasing indication for transplantation. Dietary and genetic factors determine susceptibility to NAFLD and its progression. NAFLD may also be involved in the pathogenesis of cardiovascular disease. Most patients present with incidentally found abnormal liver blood tests. Diagnosis is usually one of exclusion. Liver biopsy is required for disease staging, but new imaging modalities and biomarkers are emerging which may eventually fulfil this role. There is, as yet no firm evidence-based treatment for NAFLD. Therapy is currently directed at treating components of the metabolic syndrome which may also be beneficial for the liver. The recent elucidation of the mechanisms leading to progressive disease suggests a variety of novel targets worthy of testing in animal models of NAFLD and subsequently in pilot studies in humans.
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PMID:Non-alcoholic fatty liver disease: the mist gradually clears. 1830 79

Obesity has become epidemic in the United States, in Europe, and in many urban areas in the developing world. The globalization of certain 'fast foods' and 'soft drinks' may, in part, be contributing to this epidemic. Diets high in saturated fatty acids and trans fats as well as drinks that have high fructose corn syrup levels may be particularly harmful. Recent research suggests that fat is a dynamic endocrine organ and that visceral fat is associated with the metabolic syndrome. Central obesity leads to organ steatosis and altered serum adipokines including reduced adiponectin and markedly elevated leptin. This abnormal adipokine milieu results in increased tissue infiltration of monocytes and macrophages which produce proinflammatory cytokines that alter organ function. Over many years, the combination of steatosis and local inflammation leads to fibrosis and eventually to cancer. Nonalcoholic fatty liver disease (NAFLD) is a precursor for nonalcoholic steatohepatitis (NASH). NAFLD and NASH (1) lead to cirrhosis and hepatocellular carcinoma, (2) increase the risk of liver resection, and (3) compromise the outcome of liver transplantation. Similarly, in the pancreas nonalcoholic fatty pancreas disease (NAFPD) may lead to nonalcoholic steatopancreatitis (NASP). NAFPD and NASP may (1) promote the development of chronic pancreatitis and pancreatic cancer, (2) exacerbate the severity of acute pancreatitis, and (3) increase the risk of pancreatic surgery. In the gallbladder nonalcoholic fatty gallbladder disease (NAFGBD, cholecystosteatosis) may lead to steatocholecystitis. Cholecystosteatosis may be an explanation for (1) the increased incidence of chronic acalculous cholecystitis and (2) the increased number of cholecystectomies.
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PMID:Hepato-pancreato-biliary fat: the good, the bad and the ugly. 1833 22

Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome. The clinicopathologic spectrum 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. As yet there is no convincingly effective treatment for NAFLD and the best option for these patients might be a multimodal treatment plan targeting obesity, insulin resistance, diabetes mellitus, hyperlipidemia and hypertension.
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PMID:[Treatment of fatty liver disease]. 1840 89

The increasing prevalence of obesity, insulin resistance, and the metabolic syndrome has significant implications for the future of chronic liver disease. The resultant increase in the number of patients with nonalcoholic fatty liver disease (NAFLD) is expected to translate into increased numbers of patients with end-stage liver disease (cirrhosis), liver failure, and hepatocellular carcinoma. It is particularly important to identify the patients who are at greatest risk of these aforementioned complications of chronic liver disease, those nonalcoholic fatty liver disease patients with nonalcoholic steatohepatitis. Currently liver biopsy is the gold standard for diagnosis, but less invasive, highly accurate, and affordable screening tools are required. These tools may include radiologic or laboratory studies to identify patients noninvasively who may benefit from therapeutic interventions. Clinical scoring systems that may be used in general practice as initial screening tools also may prove useful. Most therapeutic modalities available or under development target the major pathways thought essential in the pathogenesis of nonalcoholic steatohepatitis and often are directed at reducing body mass index and improving insulin resistance via pharmacologic, surgical, dietary, or exercise regimens. Other potential therapeutic agents directed at cytoprotection or reduction of fibrosis are under investigation. This article focuses on diagnosis and therapy available and under development for this chronic liver disease.
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PMID:Diagnosis and therapy of nonalcoholic steatohepatitis. 1847 47


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