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)

The incidence of liver cancer is high in all low-resource regions of the world, with the exception of Northern Africa and Western Asia. The estimated worldwide number of new cases of liver cancer in 2002 is 600,000, of which 82% are from developing countries. Given the poor survival from this disease, the estimated number of deaths is similar to that of new cases. Hepatocellular carcinoma (HCC) is the main form of liver cancer. A part from chronic infections with Hepatitis B and Hepatitis C viruses, which are the main causes of HCC, contamination of foodstuff with aflatoxins, a group of mycotoxins produced by the fungi Aspergillus flavus and Aspergillus parasiticus, is an important contributor to HCC burden in many low-income country. Alcoholic cirrhosis is an important risk factor for HCC in populations with low prevalence of HBV and HCV infection, and the association between tobacco smoking and HCC is now established. Diabetes is also related to an excess risk of HCC and the increased prevalence of overweight and obesity likely contributes to it. The second most important type of liver cancer is cholangiocarcinoma, whose main known cause is infestation with the liver flukes, Opistorchis viverrini and Clonorchis sinensis, which is frequent in some areas in South-East Asia. Angiosarcoma is a rare form of liver cancer whose occurence is linked to occupational exposure to vinyl chloride.
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PMID:Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection. 1909 58

Patients (85%) with hepatocellular adenoma (HCA) are women taking oral contraceptives. They can be divided into four subgroups according to their genotype/phenotype features. (1) Hepatocyte nuclear factor 1alpha (HNF1alpha) biallelic somatic mutations are observed in 35% of the HCA cases. It occurs in almost all cases in women. HNF1alpha-mutated HCA are most of the time, highly steatotic, with a lack of expression of liver fatty acid binding protein (LFABP) in immunohistochemistry analyses. Adenomatosis is frequently detected in this context. An HNF1alpha germline mutation is observed in less than 5% of HCA cases and can be associated with MODY 3 diabetes. (2) An activating beta-catenin mutation was found in 10% of HCA. These beta-catenin activated HCAs are observed in men and women, and specific risk factors, such as male hormone administration or glycogenosis, are associated with their development. Immunohistochemistry studies show that these HCAs overexpress beta-catenin (nuclear and cytoplasmic) and glutamine synthetase. This group of tumours has a higher risk of malignant transformation into hepatocellular carcinoma. (3) Inflammatory HCAs are observed in 40% of the cases, and they are most frequent in women but are also found in men. Lesions are characterised by inflammatory infiltrates, dystrophic arteries, sinusoidal dilatation and ductular reaction. They express serum amyloid A and C-reactive protein. In this group, GGT is frequently elevated, with a biological inflammatory syndrome present. Also, there are more overweight patients in this group. An additional 10% of inflammatory HCAs express beta-catenin, and are also at risk of malignant transformation. (4) Currently, less than 10% of HCAs are unclassified. It is hoped that in the near future it will be possible with clinical, biological and imaging data to predict in which of the 2 major groups (HNF1alpha-mutated HCA and inflammatory HCA) the patient belongs and to propose better guidelines in terms of surveillance and treatment.
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PMID:Hepatocellular adenoma: what is new in 2008. 1966 72

Non-alcoholic steatohepatitis (NASH) has been associated with hepatocellular carcinoma (HCC) often arising in histologically advanced disease when steatohepatitis is not active (cryptogenic cirrhosis). Our objective was to characterize patients with HCC and active, histologically defined steatohepatitis. Among 394 patients with HCC detected by ultrasound imaging over 8 years and staged by the Barcelona Clinic Liver Cancer (BCLC) criteria, we identified 7 cases (1.7%) with HCC occurring in the setting of active biopsy-proven NASH. All were negative for other liver diseases such as hepatitis C, hepatitis B, autoimmune hepatitis, Wilson disease, and hemochromatosis. The patients (4 males and 3 females, age 63 +/- 13 years) were either overweight (4) or obese (3); 57% were diabetic and 28.5% had dyslipidemia. Cirrhosis was present in 6 of 7 patients, but 1 patient had well-differentiated HCC in the setting of NASH without cirrhosis (fibrosis stage 1) based on repeated liver biopsies, the absence of portal hypertension by clinical and radiographic evaluations and by direct surgical inspection. Among the cirrhotic patients, 71.4% were clinically staged as Child A and 14.2% as Child B. Tumor size ranged from 1.0 to 5.2 cm and 5 of 7 patients were classified as early stage; 46% of all nodules were hyper-echoic and 57% were <3 cm. HCC was well differentiated in 1/6 and moderately differentiated in 5/6. Alpha-fetoprotein was <100 ng/mL in all patients. HCC in patients with active steatohepatitis is often multifocal, may precede clinically advanced disease and occurs without diagnostic levels of alpha-fetoprotein. Importantly, HCC may occur in NASH in the absence of cirrhosis. More aggressive screening of NASH patients may be warranted.
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PMID:Does hepatocellular carcinoma in non-alcoholic steatohepatitis exist in cirrhotic and non-cirrhotic patients? 1978 50

Since android overweight/obesity and insulin resistance are independent risk factors for cardiovascular disease, we investigated their impact on basal and postprandial scavenger receptor BI (SR-BI) and ATP binding cassette transporter A1 (ABCA1)-mediated serum cholesterol efflux. Twelve android overweight to obese and 9 normal weight controls women underwent body composition analysis by dual energy X-ray absorptiometry, a euglycemic hyperinsulinemic clamp, and an oral fat load with blood sampling at initial time (T0), 4h (T4) and 10h (T10) after the fat load. Serum lipids and HDL-parameters, capacities of serum to promote cholesterol efflux from SR-BI expressing Fu5AH hepatoma cells or from ABCA1-expressing J774 macrophages and to abilities of serum to induce a net removal of cholesterol from macrophage foam cells were measured at T0, T4 and T10. Sera from overweight/obese exhibited moderately decreased SR-BI-mediated cholesterol efflux capacities, in accordance with reduced HDL concentrations, but importantly increased ABCA1-mediated cholesterol efflux and increased cholesterol extraction capacities over the postprandial period, partly related to higher prebeta-HDL concentrations. In multiple regression analyses, android obesity-related parameters and HDL-PL or prebeta-HDL levels remained the only independent correlates for SR-BI or ABCA1-dependent fractional cholesterol efflux while only prebeta-HDL levels remained correlated to cholesterol extraction capacities. Our results suggest that android overweight/obesity may not result in an impaired cholesterol efflux capacity.
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PMID:Impact of android overweight or obesity and insulin resistance on basal and postprandial SR-BI and ABCA1-mediated serum cholesterol efflux capacities. 1983 7

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological term that encompasses a spectrum of abnormalities ranging from simple triglyceride accumulation in the hepatocytes (hepatic steatosis) to hepatic steatosis with inflammation (steatohepatitis, also known as nonalcoholic steatohepatitis or NASH). NASH can also progress to cirrhosis and hepatocellular carcinoma (HCC). Steatohepatitis has been estimated to affect around 5% of the total population and 20% of those who are overweight. The mechanisms leading to NASH and its progression to cirrhosis and HCC remain unclear, but it is a condition typically associated with obesity, insulin resistance, diabetes, and hypertriglyceridemia. This point corroborates the need for animal models and molecular markers that allow us to understand the mechanisms underlying this disease. Nowadays, there are numerous mice models to study abnormal liver function such as steatosis, NASH, and hepatocellular carcinoma. The study of the established animal models has provided many clues in the pathogenesis of steatosis and steatohepatitis, although these remain incompletely understood and no mice model completely fulfills the clinical features observed in humans. In addition, there is a lack of accurate sensitive diagnostic tests that do not involve invasive procedures. Current laboratory tests include some biochemical analysis, but their utility for diagnosing NASH is still poor. For that reason, a great effort is being made toward the identification and validation of novel biomarkers to assess NASH using high-throughput analysis based on genomics, proteomics, and metabolomics. The most recent discoveries and their validation will be discussed.
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PMID:Nonalcoholic steatohepatitis, animal models, and biomarkers: what is new? 1995 47

Epidemiological studies indicate that overweight and obesity are associated with increased cancer risk. To study how obesity augments cancer risk and development, we focused on hepatocellular carcinoma (HCC), the common form of liver cancer whose occurrence and progression are the most strongly affected by obesity among all cancers. We now demonstrate that either dietary or genetic obesity is a potent bona fide liver tumor promoter in mice. Obesity-promoted HCC development was dependent on enhanced production of the tumor-promoting cytokines IL-6 and TNF, which cause hepatic inflammation and activation of the oncogenic transcription factor STAT3. The chronic inflammatory response caused by obesity and enhanced production of IL-6 and TNF may also increase the risk of other cancers.
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PMID:Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. 2063 47

Non-alcoholic fatty liver disease (NAFLD) is a clinico-pathologic spectrum of conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Although simple or bland steatosis follows a relatively benign clinical course, NASH can potentially progress to cirrhosis (approximately 10 to 15 percent) and hepatocellular carcinoma. NAFLD occurs in an estimated 25 to 30 percent of the US general population, while NASH is reported in 2 to 3 percent of the population. Even though common explanation for the increased prevalence of NAFLD is the increased rate of obesity, the risk of developing NAFLD and NASH is not limited to overweight and obese individuals. Currently, the only way to diagnose NASH or to assess the stage of fibrosis is by obtaining a liver biopsy. Liver biopsy is invasive, expensive, and associated with potential risks, including post biopsy pain, bleeding, organ perforation, and even death; serious complications can occur in 0.3 percent of liver biopsies with 0.01 percent being fatal. This review examines the current strategies for development of the non-invasive techniques that will one day replace liver biopsy and serve as a non-invasive gold standard for the diagnosis and staging of NASH.
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PMID:Non-invasive diagnostic tests for non-alcoholic fatty liver disease. 2019 30

Known risk factors for hepatocellular carcinoma (HCC) include hepatitis C, hepatitis B, and alcoholic liver disease. Several studies have examined diabetes as a risk factor for HCC because of its association with fatty liver disease and non-alcoholic steatohepatitis. The current study by Tung et al. found that neither diabetes nor overweight was a risk factor for HCC. Results were consistent using both a cross-sectional and a case-control study approach. Findings from this study suggest that diabetes and overweight alone are not adequate to increase the risk of HCC in the absence of concomitant viral hepatitis or liver disease.
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PMID:Diabetes and hepatocellular carcinoma: what role does diabetes have in the presence of other known risk factors? 2005 44

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases worldwide, mostly due to the dramatic increase in obesity rates. This disease presents mainly as simple liver steatosis, whereas 10-20% of patients exhibit an inflammatory phenotype referred to as non-alcoholic steatohepatitis (NASH). Advanced liver disease affects a smaller group of patients including fibrosis, cirrhosis and hepatocellular carcinoma. Higher age, extensive overweight, and number of features of the metabolic syndrome are associated with NAFLD severity. In most cases, NAFLD is associated with insulin resistance and insulin resistance is therefore a major target for all NAFLD treatment modalities. Various treatments into this direction, such as the use of thiazolidinediones have recently failed and did not lead to an improvement in liver histology parameters. Successful weight loss either achieved via bariatric surgery or subsequent to lifestyle modification/behavior therapy, however, has been demonstrated to improve both metabolic parameters and liver histology including inflammatory changes. The first recently reported randomized controlled trial in NASH patients testing the effects of weight loss showed that a one year period of lifestyle adjustment resulted in a 7-10% weight loss with significant histological improvement of liver disease. Orlistat, the only available obesity drug treatment on the market, failed to improve insulin resistance or histopathology in NAFLD. Therefore, new weight-loss inducing agents are eagerly awaited to increase the percentage of obese people to benefit from weight reduction.
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PMID:Weight loss: cornerstone in the treatment of non-alcoholic fatty liver disease. 2048 53

Nonalcoholic fatty liver disease (NAFLD) is emerging as an important cause of liver disease in India. Epidemiological studies suggest prevalence of NAFLD in around 9% to 32% of general population in India with higher prevalence in those with overweight or obesity and those with diabetes or prediabetes. Clinicopathological studies show that NAFLD is an important cause of unexplained rise in hepatic transaminases, cryptogenic cirrhosis and cryptogenic hepatocellular carcinoma in Indian patients. There is high prevalence of insulin resistance and nearly half of Indian patients with NAFLD have evidence of full-blown metabolic syndrome. Though oxidative stress is involved in the pathogenesis of NAFLD/nonalcoholic steatohepatitis, serum or liver iron and HFE gene mutations appear not to play a role in the pathogenesis of NAFLD in Indian patients. Imaging modalities are not useful in differentiating simple steatosis from NASH and liver biopsy may be useful in those with risk factors for significant liver disease. Pilot studies on treatment strategies have shown that weight reduction and exercise, ursodeoxycholic acid, metformin, vitamin E and pentoxyfylline are effective in normalizing transaminases and or in improving hepatic steatosis and inflammation in Indian patients with NAFLD. Randomized controlled treatment trials involving large number of patients with histological end point are required to assess the efficacy of different modalities. In conclusion, a lot has been done, yet more is required to understand various aspects of NAFLD in India.
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PMID:Nonalcoholic fatty liver disease in India - a lot done, yet more required! 2119 81


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