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)

Iron is essential for life, but iron overload is toxic and potentially fatal. The liver is a major site of iron storage and is particularly susceptible to injury from iron overload, especially when (as in primary hemochromatosis) the iron accumulates in hepatocytes. Iron can be taken up by the liver in several forms and by several pathways including: (1) receptor-mediated endocytosis of diferric or monoferric transferrin or ferritin, (2) reduction and carrier-facilitated internalization of iron from transferrin without internalization of the protein moiety of transferrin, (3) electrogenic uptake of low molecular weight, non-protein bound forms of iron, and (4) uptake of heme from heme-albumin, heme-hemopexin, or hemoglobin-haptoglobin complexes. Normally, pathway 2 is probably the major one for uptake of iron by hepatocytes. Iron is stored in the liver in the cores of ferritin shells and as hemosiderin, an insoluble product derived from iron-rich ferritin. Iron in hepatocytes stimulates translation of ferritin mRNA and represses transcription of DNA for transferrin and transferrin receptors. The major pathologic effects of chronic hepatic iron overload are: (1) fibrosis and cirrhosis, (2) porphyria cutanea tarda, and (3) hepatocellular carcinoma. Although precise pathogenetic mechanisms remain unknown, iron probably produces these and other toxic effects by increasing oxidative stress and lysosomal lability. Vigorous efforts at diagnosis and treatment of iron overload are essential since the pathologic effects of iron are totally preventable by early vigorous iron removal and prevention of iron re-accumulation.
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PMID:Iron and the liver. 184 76

Alcoholic liver disease includes steatosis, alcoholic hepatitis and cirrhosis. Other liver diseases of genetic origin, but with a curious association with alcohol intake, are hemochromatosis and porphyria cutanea tarda. The attribution of chronic hepatitis to alcohol intake remains speculative, and the association may reflect hepatitis C infection. Hepatic injury attributed to alcohol includes the changes reported in the fetal alcohol syndrome. Steatosis, the characteristic consequence of excess alcohol intake, is usually macrovesicular and rarely microvesicular. Acute intrahepatic cholestasis, which in rare instances accompanies steatosis, must be distinguished from other causes of intrahepatic cholestasis (e.g., drug-induced) and from mechanical obstruction of the intrahepatic bile ducts (e.g., pancreatitis, choledocholithiasis) before being accepted. Alcoholic hepatitis (steatonecrosis) is characterized by a constellation of lesions: steatosis, Mallory bodies (with or without a neutrophilic inflammatory response), megamitochondria, occlusive lesions of terminal hepatic venules, and a lattice-like pattern of pericellular fibrosis. All these lesions mainly affect zone 3 of the hepatic acinus. Other changes, observed at the ultrastructural level, are of importance in progression of the disease. They include widespread cytoplasmic shedding, and capillarization and defenestration of sinusoids. Progressive fibrosis complicating alcoholic hepatitis eventually leads to cirrhosis that is typically micronodular but can evolve to a mixed or macronodular pattern. Hepatocellular carcinoma occurs in 5 to 15% of patients with alcoholic liver disease. The clinical syndrome of alcoholic liver disease is the result of three factors--parenchymal insufficiency, portal hypertension and the clinical consequences of extrahepatic damage produced by alcohol. At the several phases of the life history of alcoholic liver disease, the individual factors play a different role. The clinical manifestations of alcoholic steatosis are mainly extrahepatic in origin. Those of alcoholic hepatitis reflect mainly parenchymal insufficiency and those of cirrhosis are mainly those of portal hypertension. Alcoholic liver injury appears to be generated by the effects of ethanol metabolism and the toxic effects of acetaldehyde, perhaps the immune responses to alcohol- or acetaldehyde-altered proteins, and questionably enhanced by viral hepatitis. Alcoholic hepatitis may be mimicked histologically, and to a varying degree clinically, by a number of conditions (obesity, diabetes, several drug-induced injuries, jejunoileal bypass, and related "shortcircuiting" of the bowel). Perhaps the most important facet of the hepatotoxicity of alcohol is its enhancement of the effects of a number of other hepatotoxic agents, among which acetaminophen is the prime example.
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PMID:Alcoholic liver disease: pathologic, pathogenetic and clinical aspects. 205 45

Primary hemochromatosis is a common genetic disorder that results in inappropriate iron absorption and storage, with progressive damage to target organs. Hepatic cirrhosis and hepatocellular carcinoma are sequelae of hemochromatosis which are potentially preventable. The diagnosis may be suspected prior to target organ damage by appropriate screening tests, and is confirmed by liver biopsy. Three cases of hemochromatosis in the precirrhotic stage of the disease are presented. The pathophysiology, clinical and laboratory features and management are discussed. The high gene frequency in the general population warrants routine screening tests in asymptomatic healthy young adults. Phlebotomy is the indicated treatment for all stages of the disease.
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PMID:Diagnosis and management of precirrhotic hemochromatosis. 215 80

Primary hepatocellular carcinoma, one of the most common malignancies in the world, develops in chronic liver diseases of different etiologies. Hepatitis B and non-A, non-B infections, alcoholic cirrhosis, hemochromatosis, contamination with aflatoxins, and oral contraceptives are just a few of the conditions that have been associated with this carcinoma. To our knowledge, few cases of autoimmune chronic active hepatitis and hepatocellular carcinoma have been reported in the literature. We describe a patient who developed hepatocellular carcinoma 21 years after the onset of the autoimmune hepatitis.
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PMID:Hepatocellular carcinoma associated with autoimmune chronic active hepatitis. 216 43

Hepadnaviruses share properties of virion structure, genome structure and replication, epidemiologic behavior, and pathogenic effects, including an association with hepatocellular carcinoma (HCC). Epidemiologic evidence implicating hepadnavirus infection in HCC includes the observation that the geographic distributions of HBV infection and HCC are similar, that the incidence of HCC is much higher in hepadnavirus infected than uninfected hosts, and that viral DNA sequences are integrated in the cellular DNA of most (e.g., 80-90%) but not all hepadnavirus-associated HCC. Cirrhosis further increases the risk of HCC in HBV infected humans. The precise role of hepadnaviruses in development of most HCC is unclear, although the finding of viral integrations within or near protooncogenes in a few cases suggests the possibility that these integrations may play a direct role in these HCC. However, in the great majority of HCC associated with HBV infections, viral integrations are in different cellular DNA sites in different HCC, integrations are not within domains of known protooncogenes, and integrations are not found in some 10-15% hepadnavirus-associated HCC, suggesting that persisting viral sequences are not directly involved in the development of these HCC as viral sequences are for tumors caused by viruses with oncogenes or viruses that act by a "promoter-insertion" mechanism. It is possible, however, that oncogenic mutations could arise via other mutagenic mechanism that may operate in chronic hepatitis B and/or cirrhosis and which do not involve persisting viral integrations. For example, liver regeneration, which is a feature of the cirrhosis associated with chronic HBV infection (and sometimes with chronic hepatitis B) involves proliferation of many cells with HBV integrations, and such integrations have been shown to be unstable and may lead to mutations through post-integration rearrangements of cellular sequences at sites of viral integrations. Viral sequences appear to be lost or deleted at some such sites of rearranged cell DNA. Chronic HBV infection shares pathologic features of liver cell injury and reactive inflammation, liver regeneration, and in man sometimes cirrhosis with other important risk factors for HCC including chronic alcoholic liver disease, chronic non-A, non-B hepatitis, hemochromatosis, and crypogenic cirrhosis, suggesting that this common pathologic process may be carcinogenic by a mechanism that does not depend specifically on the factor which initiates liver cell injury. The pathogenetic role of chronic hepadnavirus infection in such a process would be in causing liver cell injury with reactive inflammation and hepatocyte proliferation (regeneration).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hepadnaviruses in cirrhotic liver and hepatocellular carcinoma. 216 15

In the United States, a large percentage of patients with hepatocellular carcinoma are serologically negative for hepatitis B. We conducted a retrospective study to determine the prevalence of hepatitis C antibody in the sera of 59 patients with hepatocellular carcinoma who were HBsAg-negative and had no evidence of alcoholic liver disease, primary biliary cirrhosis, autoimmune hepatitis, hemochromatosis or alpha 1-antitrypsin deficiency. Twenty patients (34%) were hepatitis C antibody-positive and hepatitis B core antibody-negative. All twenty patients had underlying cirrhosis, and seven (35%) had histories of transfusions. Eleven (19%) additional patients were also hepatitis C antibody-positive but were hepatitis B core antibody-positive as well. Twenty-one (36%) patients were both hepatitis C antibody- and hepatitis B core antibody-negative and seven (12%) were hepatitis C antibody-negative but hepatitis B core antibody-positive. The prevalence of hepatitis C antibody was also determined among three other population groups serving as controls and found to be 14% in 28 HbsAg-positive patients with hepatocellular carcinoma, 44% in 76 patients with cryptogenic cirrhosis and 0.5% in 200 consecutive volunteer blood donors. We conclude that hepatitis C antibody is prevalent among patients with hepatocellular carcinoma and may therefore be a common causative agent of this disease. A significant number of patients with and without cirrhosis, negative for hepatitis C antibody and hepatitis B core antibody, remain without a discernible cause for this malignancy. Perhaps a second- or third-generation test will detect hepatitis C antibody in some of these patients.
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PMID:Hepatitis C-associated hepatocellular carcinoma. 165 57

A case of hepatocellular carcinoma in idiopathic hemochromatosis is discussed to illustrate the possible advantages of MR imaging. Since hepatic iron overload provides a natural source of paramagnetic contrast enhancement MRI should performed in preference to other investigative procedures to detect small and curative resectable hepatocellular carcinomas in patients with hemochromatosis.
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PMID:[Magnetic resonance tomography in hepatocellular carcinoma and idiopathic hemochromatosis]. 217 39

The occurrence of hepatocellular carcinoma in a 22-year-old man with thalassemia major is reported. As a result of transfusional hemochromatosis, this patient had already developed diabetes, hypogonadism, heart failure, and the sicca syndrome; he was serum and tissue HBsAg negative. Liver iron concentration measured postmortem was found to be 50 times normal. Multiply transfused patients are at risk of developing hepatocellular carcinoma. Serial measurements of serum alpha-fetoprotein should permit early detection of the tumor and reduce mortality. Preventive measures include early immunisation against hepatitis B virus and prevention of iron accumulation by intensive use of desferrioxamine. Treatment of hemochromatosis-associated hypogonadism with androgens should be considered with caution.
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PMID:Hepatocellular carcinoma in thalassemia major. 243 Dec 57

The classical morphological criteria in the diagnosis of hepatocellular carcinoma (HCC) include: (a) the similarity of tumor cells to hepatic cord cells; (b) the trabecular nature of the growth with capillary and canaliculi formation, and (c) the intravascular growth of trabecular carcinoma. These criteria apply to the most common variants of HCC but they do not suffice in all cases. That makes additional criteria and certain refinements necessary. A promising approach to the diagnosis of HCC is that based upon consideration by the pathologist of some relevant aspects of the natural history of this tumor. A panel of tests exploring the various functions and properties of liver cells should be set up. Tests for bile and fibrinogen synthesis are most important because they reflect specific and exclusive properties of the original cell line. Bile synthesis in tumor tissue is reflected by the finding of cholecholatestasis, namely bilirubinostasis and retention of copper and copper-binding proteins. The positive immunostaining for fibrinogen may appear in the form of cytoplasmic granules occurring in 50% of HCC, or in the form of fibrinogen-ground-glass (G-G) inclusions, representing a specific feature of HCC. During neoplastic transformation oncofetal proteins may reappear, alpha-fetoprotein (AFP) being very common. Despite sensitivity of AFP, this test, similar to alpha-1-antitrypsin (AAT), has very low specificity, because of the widespread occurrence of these proteins in a variety of tumors. The selection of special 'clones' such as Mallory bodies and fibrinogen-G-G is of particular value, because of the specificity of these peculiar cytoplasmic changes. Although rare, the presence of HBV antigens in tumor tissue is virtually pathognomonic for HCC. The availability of nonneoplastic liver tissue for morphological examination is of great help, because it may carry key information or markers of the development stages of HCC: cirrhosis, liver cell dysplasia, HBV antigens, congenital metabolic disorders, such as hemochromatosis and AAT deficiency. The two latter conditions represent the link with the last working hypothesis of the present study, i.e. that during neoplastic transformation hepatocytes may 'switch' their 'phenotype' thus escaping the storage phenomena, which continue to occur in nonneoplastic hepatocytes. This study provides a guideline to a dynamic approach to the diagnosis of HCC. The rationale is listed in 5 points; among them, bile production, fibrinogen synthesis, Mallory body and fibrinogen-G-G selection, HBV antigen expression can be considered at present as confident markers for the morphological diagnosis of HCC.
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PMID:Natural history of hepatocellular carcinoma as viewed by the pathologist. 283 13

Previous reports have emphasized the association of primary hepatocellular carcinoma in patients with idiopathic hemochromatosis with cirrhosis. In contrast, patients with idiopathic hemochromatosis without cirrhosis have no increased risk of hepatocellular carcinoma. Phlebotomy therapy, by preventing the accumulation of parenchymal iron and subsequent cirrhosis, is believed to prevent hepatocellular carcinoma in the precirrhotic stage of the disease. We report the case of a 67-yr-old man with a 32-yr history of idiopathic hemochromatosis complicated by cirrhosis, who had reversal of cirrhosis with phlebotomy therapy, yet developed hepatocellular carcinoma. There was no serologic or tissue evidence of hepatitis B infection.
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PMID:Primary hepatocellular carcinoma in idiopathic hemochromatosis after reversal of cirrhosis. 284 22


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