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)

Hereditary hemochromatosis is the most common cause of iron overload in adults and is probably the second most common cause of iron overload in children in the United States next to transfusional overload. Serious morbidity from this disorder of iron absorption can occur in early as well as in middle and advanced age, iron overload having been reported in children with hereditary hemochromatosis as early as 2 years of age. Younger persons differ from older persons in that the risk for iron loading in females appears to be equal to the risk for males, in contrast to a preponderance of males among older patients. Also, younger patients frequently demonstrate cardiac and gonadal involvement, with cardiac failure commonly leading to death, whereas older patients are more likely to have liver involvement and diabetes mellitus, with liver failure and hepatoma commonly leading to death. Because early diagnosis and treatment can prevent the toxicities of iron overload, appropriate screening can be lifesaving. Transferrin saturation is the most reliable screening test. Liver biopsy with objective measurement of hepatic iron stores is the most important diagnostic criterion at present, although reliable noninvasive methods for quantitating body iron are being developed. Young individuals who should be screened for iron overload include patients with cardiac myopathies, hypogonadism, amenorrhea, loss of libido, diabetes mellitus, other endocrine disorders, cirrhosis of the liver, and arthritis, as well as the siblings, parents, and children of patients with hereditary hemochromatosis or iron loading of unknown cause.
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PMID:Hereditary hemochromatosis in children, adolescents, and young adults. 305 60

Cirrhotic patients with hereditary hemochromatosis (HHC) have an increased risk of primary liver cancer (PLC). The purpose of this study was to determine the prevalence of primary liver cancer in patients with HHC undergoing orthotopic liver transplantation (OLT). Five liver transplant centers were surveyed; clinical and pathological data on 37 patients with HHC undergoing OLT were retrospectively collected and analyzed. The diagnosis of HHC was established by a combination of serum transferrin-iron saturation, hepatic iron index (HII), and/or pattern of liver iron staining. The diagnosis of HHC had been unsuspected before OLT in 13 of 37 (35%). Primary liver cancer was found in the explants of 10 of 37 patients (27%) and was unsuspected in 7 of 10 (70%); 8 were hepatocellular carcinoma, and 2 were cholangiocarcinoma; foci of hepatocyte dysplasia were found in 6 additional patients. Mean (+/- SEM) hepatic iron content and HII in 20 patients without prior phlebotomy or bleeding were 17.2 mg/g dry weight (+/- 2.9) and 5.5 (+/- 0.8), respectively. The overall 1-year survival rate after OLT in the 37 HHC patients was 58% (v 55% for HHC patients with PLC). We draw the following conclusions: (1) the diagnosis of HHC is often unsuspected before OLT, and HHC should be evaluated pretransplantation by direct and indirect markers; (2) HHC patients undergoing OLT have a high prevalence of primary liver cancer, the majority being unsuspected; and (3) HHC patients have poorer than average survival after OLT, which cannot be explained solely by the presence of concomitant PLC.
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PMID:Primary liver cancer and survival in patients undergoing liver transplantation for hemochromatosis. 934 73

Although the iron-loading disease, hereditary hemochromatosis, has a strong causal association with hepatocellular carcinoma (HCC), the carcinogenic potential of dietary iron overload in Black Africans is not known. We investigated this potential by evaluating iron status, alcohol consumption, markers for hepatitis B (HBV) and C virus (HCV) infections, and exposure to dietary aflatoxin B1 in 24 rural patients with this tumor, 48 race-, sex-, and age-matched hospital-based controls, and 75 related or unrelated close family members of the cancer patients. Iron overload was defined as a raised serum ferritin concentration in combination with a transferrin saturation > or = 60%, and was confirmed histologically when possible. Among 24 patients and 48 hospital controls, the risk of developing HCC in the iron-loaded subjects was 10.6 (95% confidence limits of 1.5 and 76.8) relative to individuals with normal iron status, after adjusting for alcohol consumption, chronic HBV and HBC infections, and exposure to aflatoxin B1. The risk of HCC in subjects with HBV infection was 33.2 (7.2, 153.4) (odds ratio [95% confidence limits]), HCV infection 6.4 (0.3, 133.5), and alcohol consumption 2.0 (0.5, 8.2). Aflatoxin B1 exposure did not appear to increase the risk of HCC. The population attributable risk of iron overload in the development of HCC was estimated to be 29%. Among 20 cancer patients and 75 family members, the risk of developing HCC with iron overload was 4.1 (0.5, 32.2). We conclude that dietary iron overload may contribute to the development of HCC in Black Africans.
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PMID:Dietary iron overload as a risk factor for hepatocellular carcinoma in Black Africans. 962 Mar 27

A case of a 62-year-old patient with hereditary hemochromatosis is reported, who developed hepatocellular carcinoma (HCC) in the absence of cirrhosis and other potential risk factors for HCC. Occurrence of HCC in patients with genetic hemochromatosis and noncirrhotic liver is a rare event which has previously been described only six times and appears to be limited to male patients.
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PMID:Hepatocellular carcinoma in a patient with hereditary hemochromatosis and noncirrhotic liver. A case report. 1044 68

The discovery of the C282Y and H63D point mutations in the hereditary hemochromatosis-associated HFE gene allows us to study the molecular basis of congenital and acquired iron overload disorders. In hereditary hemochromatosis an increased frequency of the C282Y and, to a lesser extent, of the H63D mutations has been established, but their role in other conditions associated with iron overload and their prevalence in the normal population are still under investigation. We sought to determine the presence of such mutations, and their possible involvement in the multi-step neoplastic transformation of the hepatocytes, in patients diagnosed with hepatocellular carcinoma, a frequent complication of iron-induced liver cirrhosis occurring in untreated hereditary hemochromatosis subjects. The frequency of the C282Y and H63D mutations was determined in DNA from 12 patients with hepatocellular carcinoma and with no clinical signs of hereditary hemochromatosis. The frequency of the mutations was also determined in 130 normal subjects. A germline C282Y mutation was found in none of the hepatocellular carcinoma patients; the frequency of the H63D mutation was not increased, compared to the 130 controls. The allele frequencies of the C282Y and H63D mutations in the normal population were 0.042 and 0.185, respectively. In conclusion, we suggest that the hereditary hemochromatosis-related mutations of the HFE gene do not play a significant role in the pathogenesis of hepatocellular carcinoma.
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PMID:Mutations of the HFE gene and the risk of hepatocellular carcinoma. 1066 Apr 82

HFE is a MHC class 1-like protein that is mutated in hereditary hemochromatosis. In order to elucidate the role of HFE protein on cellular iron metabolism, functional studies were carried out in human hepatoma cells (HLF) overexpressing a fusion gene of HFE and green fluorescent protein (GFP). The expression of HFE-GFP was found to be localized on cell membrane and perinuclear compartment by fluorescent microscopy. By co-immunoprecipitation and Western blotting, HFE-GFP protein formed a complex with endogenous transferrin receptor and beta(2)-microglobulin, suggesting that this fusion protein has the function of HFE reported previously. We then examined the (59)Fe uptake and release, and internalization and recycling of (125)I-labeled transferrin in order to elucidate the functional roles of HFE in the cell system. In the transfectants, HFE protein decreased the rate of transferrin receptor-dependent iron ((59)Fe) uptake by the cells, but did not change the rate of iron release, indicating that HFE protein decreased the rate of iron influx. Scatchard analysis of transferrin binding to HFE-transfected cells showed an elevation of the dissociation constant from 1.9 to 4. 3 nM transferrin, indicating that HFE protein decreased the affinity of transferrin receptor for transferrin, while the number of transferrin receptors decreased from 1.5x10(5)/cell to 1. 2x10(5)/cell. In addition, the rate of transferrin recycling, especially return from endosome to surface, was decreased in the HFE-transfected cells by pulse-chase study with (125)I-labeled transferrin. Our results strongly suggest an additional role of HFE on transferrin receptor recycling in addition to the decrease of receptor affinity, resulting in the reduced cellular iron.
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PMID:Overexpression of hemochromatosis protein, HFE, alters transferrin recycling process in human hepatoma cells. 1077 Oct 90

A mild to moderate iron excess is found in patients with liver diseases apparently unrelated to genetic hemochromatosis. Iron appears to affect the natural history of hepatitis C virus-related chronic liver diseases, alcoholic liver disease and nonalcoholic steatohepatitis by leading to a more severe fibrosis and thus aiding the evolution to cirrhosis. A higher frequency of mutations of the HFE gene, the gene responsible for hereditary hemochromatosis, is found in patients with liver diseases and increased liver iron than in normal patients. Patients with excess iron are potentially at a higher risk of developing hepatocellular carcinoma. Iron depletion therapy could interfere with fibrosis development and possibly reduce the risk of liver cancer occurrence.
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PMID:Iron and liver diseases. 1111 Jun 19

It has been suggested that excess iron may facilitate the occurrence of cancer. Patients with hereditary hemochromatosis (HH) are at high risk of developing liver cancer, and studies of limited series reported a high frequency of nonhepatic cancers. To verify whether patients with HH are at higher risk of liver cancer and other malignancies as compared with patients with non-iron-related chronic liver disease (CLD), we analyzed the occurrence of neoplasms in 230 patients with HH and 230 with non-iron-related CLD. The patients were matched by sex, age, duration of follow-up (+/-5 years), and severity of liver disease. On enrollment, the following variables were considered: hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, alcohol abuse, smoking, and a family history of cancer (first-degree relatives). The diagnosis of primary cancers was confirmed by histology. During the follow-up, hepatocellular carcinoma (HCC) developed in 49 and 29 patients (all cirrhotic patients) with HH and non-iron-related CLD, respectively, with a relative risk of 1.8 (95% confidence interval [CI] 1.1-2.9); nonhepatic cancers occurred in 20 and 11 patients, respectively, with a relative risk of 1.8 (95% CI 0.8-4). Four patients with HH and 1 with non-iron-related CLD developed 2 different primary cancers during follow-up. The risk of cancer after adjustment for alcohol abuse, smoking, and family history of cancer was 1.9 (95% CI 1.1-3.1) in the patients with HH. In conclusion, patients with HH are at high risk of both liver cancer and other malignancies, which should be carefully sought during follow-up.
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PMID:Increased cancer risk in a cohort of 230 patients with hereditary hemochromatosis in comparison to matched control patients with non-iron-related chronic liver disease. 1123 Jul 45

Hepatocellular carcinoma in patients with hereditary hemochromatosis in the cirrhotic phase is one of the complications causing greatest mortality and may present in spite of removal of excess iron by bloodletting. Hepatocellular carcinoma is usually considered to occur in cirrhotic livers and consequently measures for the early diagnosis of this complication are only recommended in this type of patient. We present the case of a 69-year-old female patient with non-cirrhotic hemochromatosis who, 6 years after undergoing successful treatment, developed hepatocellular carcinoma. This observation should be added to the 12 cases published in the literature. Criteria should be established for the early diagnosis of hepatocellular carcinoma in patients with hereditary hemochromatosis, irrespective of whether they have cirrhosis.
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PMID:[Hepatocellular carcinoma in a patient with hereditary hemochromatosis without cirrhosis]. 1126 Dec 25

The possible role of iron in facilitating the development of liver cancer is still debated. The aims of this study were to define the prevalence of the mutations 845G --> A and 187C --> G (C282Y and H63D) in the HFE gene associated with hereditary hemochromatosis in Italian patients with hepatocellular carcinoma occurring in cirrhosis and to analyze the interaction between these mutations and other established risk factors for hepatocellular carcinoma. The HFE gene mutations, performed by polymerase chain reaction, were analyzed in 81 patients (63 males, 18 females) with hepatocellular carcinoma. None of the patients had a phenotype compatible with homozygous hereditary hemochromatosis. Interaction between HFE mutations and exogenous risk factors was analyzed by collecting information on alcohol consumption, hepatitis B and C virus infections, and iron status at the time of diagnosis of chronic liver disease. This analysis was performed only in males to rule out gender influence on patients' iron status by using the case-only approach specifically designed to estimate departure from multiplicative risk ratios under the assumption of independence between genotype and environmental exposure. The prevalence of the C282Y mutation was significantly higher in patients with hepatocellular carcinoma than in normal controls (8.6% vs 1.6%, P < 0.03). At univariate analysis, iron overload was significantly associated with both HFE mutations (P < 0.0001), whereas ongoing hepatitis B virus infection was associated with the C282Y mutation (P < 0.05). By multivariate analysis, a trend for an increased risk of being positive for hepatitis virus markers (OR 2.9, CI 95% 0.9-9.5) and of having been alcohol abusers (OR 3, CI 95% 0.7-14) was observed in patients heterozygous for the HFE mutations. These data indicate that the prevalence of the main mutation associated with hereditary hemochromatosis is significantly higher in cirrhotic Italian patients with hepatocellular carcinoma compared to a normal population and suggest that heterozygotes for HFE mutations exposed to hepatitis virus infections or who had been alcohol abusers could have an increased risk of developing cirrhosis and later liver cancer than people without the mutations exposed to the same risk factors.
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PMID:Mutations in the HFE gene and their interaction with exogenous risk factors in hepatocellular carcinoma. 1150 61


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