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Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the target of hepatitis C virus (HCV) infection is the liver, it has become progressively more evident that HCV can induce diseases in numerous organs. Recently, much attention has been drawn to metabolic disorders in HCV infection. Initially, hepatic steatosis and disturbances in lipid metabolism were found to be characteristic of HCV infection, and, subsequently, a correlation was noted between HCV infection and diabetes. It is now evident that HCV, by itself, can induce insulin resistance by way of disturbing the intracellular signaling pathway of insulin by the function of HCV core protein. Insulin resistance, caused by HCV infection, evolves to type 2 diabetes when superimposed on a high-fat diet and obesity. The fact that HCV infection induces insulin resistance by the virus itself may influence the progression of chronic hepatitis and open up novel therapeutic approaches. When hepatitis C is compared with nonalcoholic steatohepatitis (NASH), there are a number of similarities and several differences. From the metabolic aspect, hepatitis C resembles NASH in numerous features, such as the presence of steatosis, serum dyslipidemia, and oxidative stress in the liver, suggesting that hepatitis C is a steatohepatitis. In contrast, there are noticeable differences between hepatitis C and NASH, in that HCV modulates cellular gene expression and intracellular signal transduction, including the activation of mitogen-activated protein (MAP) kinase and transcription factor activator protein (AP)-1, while such details have not been noted for NASH. This difference may explain the markedly higher incidence of HCC development in chronic hepatitis C compared with that in NASH. HCV infection needs to be viewed not only as a liver disease but also as a metabolic disease, and this viewpoint could open up a novel way to the molecular understanding of the pathogenesis of hepatitis C, as a virus-associated steatohepatitis (VASH).
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PMID:Metabolic aspects of hepatitis C viral infection: steatohepatitis resembling but distinct from NASH. 1586 69

Statins are among the most commonly prescribed drugs used to manage dyslipidemia. Hepatocellular carcinoma is the third leading cause of cancer mortality and its rates have recently been increasing in central and northern Europe and USA. To quantify the association between statin use and risk for HCC, we performed a meta-analysis of published studies. We conducted a MEDLINE search for observational studies reporting the association between exposure to statins and risk for incident liver cancer until March 2012. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Moreover, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Five observational studies (two case-control and three cohort studies) based on 2574 cases of HCC were included. Statin treatment, compared with no treatment, was inversely related to HCC (summary RR=0.58; 95% CI 0.46-0.74). Between-study heterogeneity was significant (P<0.001) and numerically relevant (I=65%). When only longest statin use was considered, the RR was 0.66 (95% CI 0.55-0.80). Influence analysis on the overall estimate showed that heterogeneity was largely because of one study; when omitting it, the I dropped to 27% (P=0.240), whereas the summary RR was only marginally modified (RR=0.52; 95% CI 0.44-0.62). There was no evidence of publication bias. This meta-analysis suggests a favorable effect of statins on HCC, in the absence, however, of a duration-risk relationship.
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PMID:Statins and primary liver cancer: a meta-analysis of observational studies. 2301 Sep 49

Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as an important public health problem nowadays. NAFLD encompass a variety of liver pathologies including simple steatosis, NASH, fibrosis, cirrhosis and finally cancer. It is associated with obesity, metabolic syndrome, dyslipidaemia, Insulin resistance (IR) and type 2 diabetes. It is the most common chronic liver disease in USA and considered to be increasing in Asia Pacific region including South Asia however there is no community based study from Pakistan. Customarily NAFLD had been regarded as a benign disease; however clinical as well as epidemiological studies had contradicted this belief because approximately 20% of the patients with NAFLD had NASH which has propensity to develop cirrhosis and ultimately to HCC. The diagnosis of NAFLD is made most of the times incidentally on abdominal imaging which is done for other purposes. Despite its prevalence, treatment options are very limited. However modification of risk factors such as dyslipidemia, diabetes control and weight reduction does help in NAFLD. Fatty liver results due to lack of physical activity; hence foremost step to manage such patients would be to develop the healthy life style. We need population based studies in our country so that we can protect our population from a new epidemic.
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PMID:Are we ready for a new epidemic of under recognized liver disease in South Asia especially in Pakistan? Non alcoholic fatty liver disease. 2386 41

Nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), leads to fibrosis and potentially cirrhosis, liver failure, and hepatocellular carcinoma, and is one of the most common causes of liver disease worldwide. NAFLD has also been implicated in other medical conditions such as insulin resistance, obesity, metabolic syndrome, hyperlipemia, hypertension, cardiovascular disease, and diabetes. Continuous hyperglycemia has been implicated in the pathogenesis of diabetic micro- and macro-vascular complications via various metabolic pathways, and numerous hyperglycemia-induced metabolic and hemodynamic conditions exist, including the increased generation of various types of advanced glycation end-products (AGEs). We recently demonstrated that glyceraldehyde-derived AGEs (Glycer-AGEs), the predominant components of toxic AGEs (TAGE), played an important role in the pathogenesis of angiopathy in diabetic patients. Moreover, a growing body of evidence suggests that the interaction between TAGE and the receptor for AGEs may alter intracellular signaling, gene expression, and the release of pro-inflammatory molecules and also elicits the generation of oxidative stress in numerous types of cells including hepatocytes and hepatic stellate cells. Serum levels of TAGE were significantly higher in NASH patients than in those with simple steatosis and healthy controls. Moreover, serum levels of TAGE inversely correlated with adiponectin (adiponectin is produced by adipose tissue and is an anti-inflammatory adipokine that can increase insulin sensitivity). Furthermore, immunohistochemical staining of TAGE showed intense staining in the livers of patients with NASH. Serum levels of TAGE may be a useful biomarker for discriminating NASH from simple steatosis. The administration of atorvastatin (10 mg daily) for 12 months significantly improved NASH-related metabolic parameters and significantly decreased serum levels of TAGE. The steatosis grade and NAFLD activity score were also significantly improved. These results demonstrated that atorvastatin decreased the serum levels of TAGE in NASH patients with dyslipidemia and suggest the usefulness of TAGE as a biomarker for the attenuation of NASH. Serum levels of TAGE were significantly higher in non-B or non-C hepatocellular carcinoma (NBNC-HCC) patients than in NASH subjects without HCC or control subjects. TAGE may be involved in the pathogenesis of NBNC-HCC, and could, therefore, be a biomarker that could discriminate NBNC-HCC from NASH. We propose that serum levels of TAGE are promising novel targets for the diagnosis of and therapeutic interventions against NASH.
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PMID:Serum levels of toxic AGEs (TAGE) may be a promising novel biomarker in development and progression of NASH. 2569 14