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)

Nonalcoholic steatohepatitis (NASH) is a condition characterized by excessive deposition of fat in the liver (steatosis), inflammation and hepatocellular necrosis. While steatosis alone is generally a benign and stable condition, NASH can have a dire prognosis in a minority of patients, mainly because of fibrosis occurrence and progression to cirrhosis. Life-threatening complications such as liver failure and hepatocellular carcinoma have been described in NASH-induced cirrhosis. Insulin resistance is almost universally found in patients with NASH and the main risk factors for this condition are overweight and diabetes. Improvement in insulin sensitivity, whether achieved by diet, exercise and/or pharmacological interventions, results in a dramatic reduction of liver fat and inflammation and fibrosis as well. Therefore NASH should be viewed as the hepatic phenotypic manifestation of insulin resistance and a bona fide component of the metabolic syndrome. Liver injury should be assessed in diabetic and/or obese patients and the mechanisms by which insulin resistance promotes liver damage needs to be elucidated. The encouraging results of the use of PPARgamma agonists and, in particular, rosiglitazone, in human or experimental models of NASH, justifies future large-scale, randomized controlled trials.
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PMID:[Nonalcoholic steatohepatitis]. 1595 6

Non-alcoholic fatty liver disease (NAFLD) has become the most common form of hepatic disorders in the developed world. NAFLD is part of the metabolic syndrome with insulin resistance as a primary underlying derangement. The natural history of NAFLD may extend from simple steatosis over steatohepatitis into cirrhosis and hepatocellular carcinoma. Among numerous factors shaping these transitions, uncoupling protein-2 (UCP2) may theoretically contribute to every stage of this disease. UCP2 is a recently identified fatty acid-responsive mitochondrial inner membrane carrier protein showing wide tissue distribution with a substantially increased presence in fatty liver. The biological functions of UCP2 are not fully elucidated and the greater part of our current knowledge has been obtained from animal experiments. These data suggest a role for UCP2 in lipid metabolism, mitochondrial bioenergetics, oxidative stress, apoptosis, and even carcinogenesis. Available evidence is reviewed and new concepts are considered to appraise the potential role of UCP2 in the pathogenesis of NAFLD.
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PMID:Uncoupling protein-2 and non-alcoholic fatty liver disease. 1597 Apr 80

The association of metabolic disorders with liver disease is receiving increasing attention in the gastroenterological community. Cohort studies have shown that advanced liver disease may stem from metabolic disorders, via fatty liver, non-alcoholic steatohepatitis, cryptogenic cirrhosis, and eventually hepatocellular carcinoma. In both obesity and diabetes, deaths from cirrhosis are higher than expected, mainly in subjects with no or moderate alcohol consumption, but high rates of fatty liver disease have been associated with all features of the metabolic syndrome. Also the risk of hepatocellular carcinoma is higher than normal, being dependent on body mass index (BMI) in obesity, and independent of age, BMI, gender and race in diabetes. Finally, metabolic liver disease may interact with hepatitis C virus infection, increasing the risk of steatosis and liver disease progression, as well as reducing the chances of an effective antiviral treatment. There is evidence that treatments aimed at reducing insulin resistance are also effective in improving liver histology. Although cardiovascular disease remains the major cause of increased morbidity and excess mortality in metabolic disorders, the risk of progressive liver disease should no longer be underestimated, being a threat to millions of people at risk in the present epidemics of obesity and diabetes, and therapeutic strategies need to be tested.
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PMID:Is liver disease a threat to patients with metabolic disorders? 1617 69

Metabolic syndrome represents a common risk factor for premature cardiovascular disease and cancer whose core cluster includes diabetes, hypertension, dyslipidaemia and obesity. The liver is a target organ in metabolic syndrome patients in which it manifests itself with non-alcoholic fatty liver disease spanning steatosis through hepatocellular carcinoma via steatohepatitis and cirrhosis. Given that metabolic syndrome and non-alcoholic fatty liver disease affect the same insulin-resistant patients, not unexpectedly, there are amazing similarities between metabolic syndrome and non-alcoholic fatty liver disease in terms of prevalence, pathogenesis, clinical features and outcome. The available drug weaponry for metabolic syndrome includes aspirin, metformin, peroxisome proliferator-activated receptor agonists, statins, ACE (angiotensin I-converting enzyme) inhibitors and sartans, which are potentially or clinically useful also to the non-alcoholic fatty liver disease patient. Studies are needed to highlight the grey areas in this topic. Issues to be addressed include: diagnostic criteria for metabolic syndrome; nomenclature of non-alcoholic fatty liver disease; enlargement of the clinical spectrum and characterization of the prognosis of insulin resistance-related diseases; evaluation of the most specific clinical predictors of metabolic syndrome/non-alcoholic fatty liver disease and assessment of their variability over the time; characterization of the importance of new risk factors for metabolic syndrome with regard to the development and progression of non-alcoholic fatty liver disease.
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PMID:Review article: the metabolic syndrome and non-alcoholic fatty liver disease. 1622 69

The incidence of hepatocellular carcinoma is increasing, but the temporal changes of risk factors remain unclear. A significant proportion of hepatocellular carcinoma (7-30%) develops in cryptogenic cirrhosis, and may represent the most worrisome complication of non-alcoholic steatohepatitis. Non-alcoholic steatohepatitis is tightly related to insulin resistance and several features of the metabolic syndrome, i.e obesity, type 2 diabetes and dyslipidaemia. Nearly two-thirds of adults in the United States and an increasing percentage of the population worldwide are overweight or obese. Diabetes prevalence is increasing as well. The rising prevalence of risk factors associated with non-alcoholic steatohepatitis can partially account for the increasing incidence of cryptogenic cirrhosis and subsequent hepatocellular carcinoma. Moreover, recent evidence demonstrates that both obesity and diabetes are per se associated with an increased cancer risk. Large prospective studies show a significant association with obesity for several cancers, including cancers of the colon, female breast, endometrium, kidney, oesophagus and liver (hepatocellular carcinoma). Type 2 diabetes is also related with increased risks of colon, endometrial, kidney, pancreatic cancer and hepatocellular carcinoma. In western countries, the insulin resistance syndrome is emerging as a risk factor for a wide variety of cancers, including hepatocellular carcinoma.
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PMID:Review article: steatosis, the metabolic syndrome and cancer. 1622 71

Chronic hepatitis C is highly heterogeneous in clinical presentation and outcomes. This heterogeneity is largely related to host factors that have been clearly proven to affect the severity and rapidity of disease progression. The most relevant factors that have been shown to accelerate progression to cirrhosis include age at infection, alcohol abuse and the metabolic syndrome with insulin resistance, obesity and hepatic steatosis. Co-infection with HIV and/or HBV also increases the risk of progression to cirrhosis and to hepatocellular carcinoma. Surprisingly enough, viral related factors appear as less important and neither the virus genotype and load have been found to exert a clear influence on disease severity and progression, although more data in this field, and particularly on the role of different viral proteins in causing cytopathic effects, are awaited and may change this view in the near future.
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PMID:Review article: chronic hepatitis C--natural history and cofactors. 1622 79

Non Alcoholic Fatty Liver Disease (NAFLD), with prevalence of 10-51% in general population involving all ages, is the major cause of elevation of ALT and a common finding by ultrasound screening and may range from simple steatosis, to Non Alcoholic Steatohepatitis (NASH) and its clinical consequences as cirrhosis and hepatocellular carcinoma. In this review will be analyse factors influencing the onset of the disease. NAFLD, primarly associated with insulin resistance, is in fact considered the hepatic manifestation of the metabolic syndrome: a cluster of disorder that includes obesity, diabetes mellitus, dyslipidaemia, arteriosclerosis and hypertension. The increased incidence and prevalence of obesity and diabetes may explain growing interest in NAFLD. Racial, ethnic, enviromental and behaviour models are also reviewed.
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PMID:Nonalcoholic fatty liver disease: defining a common problem. 1623 86

Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as one of the most common causes of chronic liver damage in the western world. It is strongly associated with insulin resistance, obesity and other features of the metabolic syndrome. The entity NAFLD embraces a clinical spectrum from benign steatosis over steatohepatitis to hepatic cirrhosis with its complications liver failure and hepatocellular carcinoma. Treatment is currently based on prescriptive diet and physical exercise. A well-defined pharmacotherapy of NAFLD still remains to be established due to the lack of randomized, controlled trials. Yet, for several drugs such as Metformin and Thiazolidinediones, smaller trials report promising results.
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PMID:[Therapeutic options for nonalcoholic fatty liver disease and steatohepatitis]. 1624 33

It is generally accepted that non-alcoholic fatty liver disease will be the most frequent liver disease in the near future and that the management of patients with non-alcoholic fatty liver disease will be a challenge for hepatologists in the next decades. Non-alcoholic fatty liver disease is considered the hepatic manifestation of the metabolic syndrome, in which insulin resistance plays a crucial role. Although steatosis will often not progress to severe liver disease, in some patients, it results in cirrhosis and even hepatocellular carcinoma. Therefore, it is important to identify those patients at risk for developing fibrosis. Age, diabetes, obesity and hypertriglyceridaemia are independent risk factors for fibrosis in patients with elevated serum alanine aminotransferase levels and steatosis on ultrasound. The presence of multiple metabolic disorders increases the risk. Apart from diet, exercise and correction of underlying metabolic abnormalities, no specific treatment is available at the moment. Theoretically, thiazolidinediones are an attractive way to treat non-alcoholic fatty liver disease, because they improve insulin resistance. Some preliminary studies with thiazolidinediones were encouraging, as steatosis, inflammation and fibrosis improved in a substantial number of patients. Although no serious side effects occurred in the pilot studies, we should look vigilantly for hepatotoxicity, as the first generation thiazolidinediones proved to be toxic for the liver.
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PMID:Review article: the treatment of non-alcoholic steatohepatitis with thiazolidinediones. 1626 63

NAFLD is a very common asymptomatic liver condition that may progress to cirrhosis and hepatocellular carcinoma, and a relation to the different components of the metabolic syndrome has been found. In this review we highlight some of the epidemiological aspects of the two disorders and discuss some of the possible mechanisms and questions to be answered concerning the risk factors for the progression of this condition, as well as the need for more studies to focus on possible modalities of treatment.
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PMID:Non-alcoholic fatty liver disease and metabolic syndrome: what we know and what we don't know. 1636 77


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