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 presence of steatosis and inflammatory infiltrate in liver biopsies is essential for the diagnosis of non-alcoholic steatohepatitis (NASH). These findings are similar to those with alcoholic liver disease. However, in the NASH-situation alcohol doesn't play an important role. Risk factors for the development of NASH are obesity and diabetes. Most of the patients are clinically asymptomatic. This means, that a diagnosis of NASH is a diagnosis of exclusion: Viral induced, autoimmune, metabolic and toxic liver disease have to be excluded. The disease has a benign clinical course. The risk of cirrhosis is low. So far, there is no established treatment. Preliminary reports suggest a positive effect of weight-loss and ursodeoxycholic acid. Wilson's disease, a copper storage disorder, in which biliary copper excretion is reduced, is inherited as an autosomal recessive trait. Most patients with Wilson disease become symptomatic between the ages of 6 and 15. In about 90% of patients serum ceruloplasmin levels and serum copper concentrations are reduced. Copper excreation is increased. Histologic examination of liver biopsy specimens reveals fatty infiltration, Mallory bodies and ballooned glycogen nuclei, abnormalities which are also found in alcoholic liver disease. The definitive diagnostic parameter is the quantitative determination of liver copper content (> 250 micrograms/g dryweight). Untreated Wilson disease is always fatal. Lifelong treatment with anti-copper drugs are essential, D-penicillamine being the firstline therapy. Hereditary hemochromatosis (HH) is an iron overload disease inherited as an autosomal recessive trait. The frequency of the disease is high. The first symptoms usually can be found at the age of 20-50 years. Arthralgia develops in up to 50% of the patients. Many organs are involved, most often the liver. The organ is usually enlarged, transaminases are always moderately elevated. Laboratory findings disclose a marked elevation in serum ferritin and transferrin saturation. More than 80% of HH-patients are homozygous for the C282Y-mutation in the HFE-gene. The firstline treatment of HH is phlebotomy. Treatment is lifelong. When serum ferritin drops below 50 micrograms/l, the frequency of phlebotomy should be reduced (4-12 per year). If the patient already has cirrhosis, the risk of HCC is very high.
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PMID:[Rare, but important chronic liver diseases]. 1250 71

Hereditary hemochromatosis is a prevalent genetic disorder of iron hyperabsorption leading to hyperferremia, tissue iron deposition and complications including cirrhosis, hepatocarcinoma, cardiomyopathy and diabetes. Most individuals affected with hereditary hemochromatosis are homozygous with respect to a missense mutation that disrupts the conformation of HFE, an atypical HLA class I molecule (ref. 1; OMIM 235200). Mice lacking Hfe or producing a C282Y mutant Hfe protein develop hyperferremia and have high hepatic iron levels. In both humans and mice, hereditary hemochromatosis is associated with a paucity of iron in reticuloendothelial cells. It has been suggested that HFE modulates uptake of transferrin-bound iron by undifferentiated intestinal crypt cells, thereby programming the absorptive capacity of enterocytes derived from these cells; however, this model is unproven and controversial. Hepcidin, a peptide hormone (HAMP; OMIM 606464), seems to act in the same regulatory pathway as HFE. Although expression of mouse Hamp is normally greater during iron overload, Hfe-/- mice have inappropriately low expression of Hamp. We crossed Hfe-/- mice with transgenic mice overexpressing Hamp and found that Hamp inhibited the iron accumulation normally observed in the Hfe-/- mice. This argues against the crypt programming model and suggests that failure of Hamp induction contributes to the pathogenesis of hemochromatosis, providing a rationale for the use of HAMP in the treatment of this disease.
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PMID:Constitutive hepcidin expression prevents iron overload in a mouse model of hemochromatosis. 1270 88

To assess the relevance of altered iron metabolism, hemoglobin electrophoresis by isoelectric focusing was performed for 16 cases of hepatocellular carcinoma (HCC) from the Liver Unit, Yangon General Hospital. Serum iron, total iron binding capacity, serum ferritin and free iron were also determined. Hemoglobin A (HbA) was found in all of the cases. Four cases had one extra band, hemoglobin A(2) in three cases, and hemoglobin F in one case. No abnormal hemoglobin was detected. Anemias due to chronic disorders or associated with liver disease were observed in all of the cases. Iron overload was documented in 83% and free iron was detected in all cases. Viral markers like HBsAg, AntiHBc, and AntiHCV singly or in combination were found in all cases. HCC occurring at young age was seen in this study; the youngest patient was 23 years old and four cases (25%) were under 40 years, with a mean age of 49 years. The findings support the hypothesis that free iron and iron overload is a potential promoter of the development of HCC, especially if underlying chronic viral infection is present.
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PMID:Hemoglobinopathies, Iron Overload and Chronic Viral Hepatitis in Patients with Hepatocellular Carcinoma in Myanmar. 1271 79

Hepatocellular carcinoma (HCC) frequently complicates hepatic cirrhosis secondary to viral infection or iron overload. Therefore, patients affected by thalassaemia syndromes have a theoretically high risk of developing the tumour. We collected data on patients attending Italian centres for the treatment of thalassaemia. Twenty-two cases of HCC were identified; 15 were male. At diagnosis, the mean age was 45 +/- 11 years and the mean serum ferritin was 1764 +/- 1448 microg/l. Eighty-six percent had been infected by hepatitis C virus. Nineteen of 22 cases were diagnosed after 1993, suggesting that this problem is becoming more frequent with the aging population of thalassaemia patients.
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PMID:Hepatocellular carcinoma in the thalassaemia syndromes. 1467 16

The present study analyzes the iron mobilization, the cytoprotective, and the antiproliferative effects of the lipophilic hydroxypyridinone CP411, in comparison with the hydrophilic chelator CP20 or deferiprone used in the treatment of iron overload. Primary rat hepatocyte cultures and the rat hepatoma cell line Fao were used. Chelator cell uptake was evaluated by mass spectrometry in the two models. This method was also used to investigate the stability of the chelators in an acellular system as well as their scavenging and chelating effects against the hydroxyl radical generated by the Fenton reaction. The iron mobilization and the cytoprotective effects of the chelators were evaluated in primary cultures by measuring respectively 55Fe and lactate dehydrogenase release in the culture medium. The antiproliferative effect of the chelators was studied using the Fao cell line and measuring DNA synthesis by thymidine incorporation and DNA content by flow cytometry. We observed that CP411 entered the hepatocytes and the Fao cells respectively 4 and 13 times more than CP20. CP411 was 2.5 times more effective than CP20 to mobilize iron from preloaded hepatocytes. Pretreatment of the hepatocytes with CP20 or CP411 decreased the toxic effect of iron and CP411 was 1.6 times more effective than CP20. A dose-dependent decrease of DNA synthesis, correlated to an accumulation of cells in S phase, was observed in the Fao cell line in the presence of CP411, while CP20 was without effect. CP411 effect was inhibited by addition of iron simultaneously with the chelator, the addition of Zn or Cu was without effect. The inhibitory effect of CP411 was reversible since, 24hr after removal of the chelator, DNA replication reached the control level. The results show that CP411 is more efficient to protect the hepatocyte from the toxic effect of iron load and to inhibit tumor cell proliferation. Its higher efficiency may result from its better cell uptake since equimolar solutions of the two chelators in an acellular system exhibit the same ability to inhibit the Fenton reaction.
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PMID:Iron mobilization, cytoprotection, and inhibition of cell proliferation in normal and transformed rat hepatocyte cultures by the hydroxypyridinone CP411, compared to CP20: a biological and physicochemical study. 1504 65

Recent research suggests an increase in the incidence of hepatocellular carcinoma (HCC) in the United States, which may be related to an upsurge in the sequelae of chronic liver disease from hepatitis C virus. In addition to factors related to the underlying etiology of liver disease, a number of host factors such as age, gender, and ethnic background may be associated with this increased risk. The aim of this study was to evaluate a number of potential risk factors for HCC in patients with cirrhosis. Patients with biopsy proven HCC were identified from our pathology and cancer registry databases. All those without histologic or clinical cirrhosis and non-HCC hepatic malignancies were excluded. Cirrhotic patients without HCC were also selected from the Cleveland Clinic unified transplant database and were designated controls. Extensive clinicodemographic data were obtained from the databases and chart reviews. When available, paraffin-embedded liver biopsy blocks were obtained for HFE gene analysis. Univariate comparisons were made with chi-square and Fisher's exact test and multivariate analysis was carried out with logistic regression. A total of 760 patients were included in this study, 244 documented cases of HCC and 516 cirrhotic controls without HCC. Patients' age (RR = 3.1 [2.6-3.8]; P < 0.0001), male gender (RR = 3.4 [2.3-5.1]; P < 0.0001), African-American ethnicity (RR = 3.1 [1.6-5.8]; P = 0.0005), and other non-Caucasian ethnicity (RR = 6.9 [3.2-14.4]; P < 0.0001) were independently associated with HCC. Restricting the analysis to HCV-related cirrhosis, the same risk factors remained independently associated with HCC: age (decade; RR = 2.3 [1.6-3.4]; P < 0.0001), male gender (RR = 2.9 [1.2-7.0]; P = 0.02), African-American ethnicity (RR = 3.1 [1.3-7.4]; P = 0.009), and other non-Caucasian ethnicity (RR = 15.8 [1.9-134]; P = 0.01). Iron studies did not reveal an increased risk for iron overload or HFE mutation. Male gender, advancing age, and non-Caucasian ethnic background are independently associated with HCC.
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PMID:Risk factors for hepatocellular carcinoma in patients with cirrhosis. 1525 8

One of the most common genetic causes of iron overload is hereditary hemochromatosis (HHC), a condition characterized by overabsorption of dietary iron from the gastrointestinal tract. This condition can lead to excessive iron accumulation with resulting dysfunction in multiple organs, including the liver, skin, heart,joints, pancreas, and testes. The clinical consequences of HHC if undetected and untreated can be severe and include liver cirrhosis,hepatocellular carcinoma, diabetes mellitus, cardiac arrhythmias and failure, arthritis, and hypogonadism. HHC is one of the most common heritable conditions in white populations of Northern European origin. This article presents a case study of HHC, describing inheritance and genetics, disease characteristics and natural history, diagnosis, differential diagnosis, and management.
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PMID:Clinical consult: iron overload--hereditary hemochromatosis. 1533 Dec 58

Although iron is essential for cell replication and survival, an increase of body iron stores has been implicated in the development of cancer. However, while the association between iron overload and hepatocellular carcinoma is well documented, the relationship with nonhepatocellular malignancies remains ill-defined. In this review, we briefly report the present knowledge regarding the association between iron overload and hematologic malignancies.
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PMID:Iron overload and hematologic malignancies. 1544 63

The incidence of hepatocellular carcinoma (HCC) is increasing in North America, Europe, and Japan, caused largely by the high rates of chronic hepatitis C virus (HCV) infection. In such individuals, the risk factors for developing HCC are advancing age, male gender, worsening hepatic fibrosis (particularly cirrhosis), and greater degrees of hepatic inflammation. Additional, potentially modifiable risk factors include coinfection with hepatitis B, excessive alcohol use, iron overload, and diabetes/obesity. Thus, approaches to preventing HCC should focus on eradicating HCV infection, responsible for the inflammation and fibrosis, and also on treating or reducing the modifiable risks, such as through hepatitis B vaccination, decreasing alcohol use, phlebotomy for iron overload, and weight control and diabetes prevention. These approaches have yet to be proven effective. Meta-analyses of standard interferon monotherapy trials in patients with HCV-related cirrhosis suggest that interferon has a small but significant effect on reducing HCC risk, particularly in those who achieve a sustained response. Other studies indicate that the reduction in HCC is greatest if a response is achieved before cirrhosis develops. Secondary prevention when HCC has been ablated or resected may be partially effected with interferon treatment or oral polyprenoic acid. No long-term studies of the effect of the currently recommended regimen of peginterferon and ribavirin have been reported, and no current trials include untreated control groups. Studies of maintenance peginterferon therapy in virological nonresponders are under way in the hope of proving that this approach is effective in decreasing the risk of HCC.
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PMID:Prevention of hepatitis C virus-related hepatocellular carcinoma. 1550 97

Hereditary hemochromatosis (HH) is associated with an increased risk for hepatocellular carcinoma (HCC). The risk previously had been estimated to be as high as 200-fold increased. Recent studies suggest that the risk for HCC in HFE -associated HH may be much lower and occurs predominantly in patients with cirrhosis at the time of diagnosis. The risk for HCC also is increased among patients with African iron overload and possibly in other iron-loading disorders such as homozygous beta thalassemia. The greatly increased iron stores in the liver observed in these disorders can stimulate carcinogenesis via both direct and indirect pathways. The prevalence of HCC also appears to be higher among patients with end-stage liver disease undergoing liver transplantation. It is not clear whether mildly to moderately increased hepatic iron stores or HFE mutations are associated independently with an increased risk for HCC among patients with other types of liver disease. In this article, the incidence and prevalence of HCC in patients with HH and other liver diseases associated with iron overload are discussed as well as the possible mechanisms for the increased risk for hepatic carcinogenesis in these disorders.
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PMID:Iron, hemochromatosis, and hepatocellular carcinoma. 1550 7


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