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)

Genetic hemochromatosis is an autosomal recessive disease, characterized by an increased iron absorption, leading to progressive iron overload. The fully expressed phenotype comprises fatigue, skin pigmentation, liver disease with hepatomegaly, cirrhosis and hepatocellular carcinoma, and diabetes. Arthralgias are frequent, cardiopathy or impotence may occur. This presentation is now unfrequent with earlier diagnosis, and patients are often asymptomatic--with only biochemical expression--or pauci-symptomatic (mild fatigue, arthralgias or increased transaminases). Transferrin saturation is always increased. Serum ferritin is proportional to iron burden. Diagnosis is now easy, since most patients are homozygote for the C282Y mutation of the HFE gene. Liver biopsy can be useful to quantify iron overload and assess liver fibrosis. The disease can be lethal due to liver disease, carcinoma or heart disease, but life expectancy goes to normal if patients are treated before the occurrence of cirrhosis. Treatment relies on regular venesections. Familial screening is essential.
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PMID:[Diagnosis and treatment of genetic hemochromatosis]. 1086 97

Hereditary hemochromatosis is the most commonly inherited autosomal recessive disorder. Hemochromatosis is a current or potential progression of abnormally high accumulations of iron in the liver. If left untreated, the condition can lead to chronic or irreversible hepatic fibrosis, cirrhosis, hepatocellular carcinoma, arthritis, and organ failure. Common signs and symptoms seen in the primary care setting include fatigue, weakness, abdominal pain, palpitations, skin pigmentation changes, and arthropathy, but any symptom associated with organ damage may be reported. Because prompt intervention can cease or reverse the debilitating effects of iron overload, prompt disease diagnosis and treatments are imperative.
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PMID:Detecting hereditary hemochromatosis. 1091 30

Primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are chronic progressive cholestatic diseases that frequently lead to biliary cirrhosis. The exact pathogenesis of these diseases remains elusive but is likely immunologically based. Complications range from fatigue and pruritus to end-stage liver disease. The risk of developing hepatocellular carcinoma is low for patients with PBC, whereas cholangiocarcinoma is common in PSC and carries an ominous prognosis. Although ursodeoxycholic acid is effective in slowing the progression of PBC, no effective medical therapy exists for PSC. Liver transplantation is the only option for patients with end-stage liver disease and yields excellent long-term survival in both groups.
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PMID:Biliary tract inflammatory disorders: primary sclerosing cholangitis and primary biliary cirrhosis. 1098 Sep 34

End-stage liver disease due to chronic hepatitis C is the leading indication for orthotopic liver transplantation in the United States. Twenty percent to 30% of hepatitis C patients are at increased risk of developing cirrhosis, and 1% to 4% of cirrhotic patients will develop hepatocellular carcinoma. These findings warrant treatment for hepatitis C virus (HCV)-infected patients. Currently, the mainstay in treatment of HCV is the use of recombinant alpha interferon, or its equivalent, in combination with the oral antiviral agent ribavirin. The major goals of therapy are clearance of the virus, achieving a noninfectious state, and halting the necro-inflammatory process that leads to fibrosis and progression to cirrhosis. End of treatment response (ETR) is biochemical and virological remission-- normalization of serum aminotransferase (ALT) and undetectable levels of HCV RNA, at the end of therapy. Sustained virological response (SVR) is defined as the absence of viremia and persistently normal aminotransferase 6 months off treatment, and is the ultimate goal of therapy. Patients who achieve SVR will have significant and persistent histologic improvement. HCV genotype, pretreatment levels of HCV-RNA (viral load), the presence of advanced fibrosis or cirrhosis, gender, and age are independent predictors of response. Ribavirin is teratogenic, therefore, contraception is mandatory for both males and females during and up to 6 months after therapy. Side effects of combination therapy are dose-dependent and most commonly include symptoms of irritability, depression and fatigue, and laboratory evidences of leukopenia, thrombocytopenia, and hemolytic anemia.
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PMID:Hepatitis C. 1109 32

Biliary tract cancer is the second most common primary hepatobiliary cancer, after hepatocellular carcinoma. The most frequent localisation is the gallbladder. Mean age of diagnosis is 65 years. The exact cause remains unknown despite well documented risk factors. The majority of these tumours are adenocarcinomas. Symptoms, frequently non specific, are occasionally typical including jaundice, right upper quadrant mass or fatigue and weight loss. Magnetic resonance imaging is becoming the main diagnostic tool, replacing retrograde or transhepatic cholangiography. Surgical resection remains the only treatment that may allow long term survival. However, it is possible in only one third of patients.
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PMID:[Biliary tract cancers]. 1121 56

We report the case of a 66-year-old male with ulcerative colitis diagnosed in 1987, who had been treated with azathioprine (AZA) for the past two years (average dose about 1.6 mg/kg/day). In May 1999 he presented with painless jaundice, fatigue and recent weight loss. Cholestatic enzymes were elevated, alpha-fetoprotein was normal and hepatitis B/C serology negative. After diagnosis of veno-occlusive disease (VOD) and hepatocellular carcinoma (HCC) via biopsy, tumour resection was performed. The histology was typical for a well-differentiated HCC with trabecular and pseudoglandular structures. Neighbouring liver tissue was atrophic, with nodular regenerative hyperplasia (NRH), peliosis-like sinusoidal ectasias and intra-sinusoidal accumulation of blood, associated with peri-sinusoidal fibrosis. Although none of the well-established risk factors for HCC such as cirrhosis, hepatitis B/C, metabolic liver disease or toxins were present, this patient developed HCC. This and previous reports suggest that NRH and/or VOD associated with AZA represent a risk factor for HCC. AZA should therefore not only be stopped in patients with NRH/VOD but patients should also be screened for HCC.
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PMID:Veno-occlusive disease, nodular regenerative hyperplasia and hepatocellular carcinoma after azathioprine treatment in a patient with ulcerative colitis. 1129 51

Hepatitis C is a common infection with worldwide prevalence. It has a variable course and can lead to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Until recently alpha-interferon (IFN-alpha) was the only effective treatment available. Combination therapy with IFN-alpha and ribavirin has been found to be more efficacious than IFN-alpha alone. Various side effects have been ascribed to interferon, such as arthralgias, myalgias, fatigue, and gastrointestinal and neuropsychiatric symptoms. Interstitial pneumonitis is a rare but known complication of IFN-alpha when given at a high dosage of 6 to 10 million units per day. Ribavirin is associated with dose-dependent hemolytic anemia, cough, dyspnea, rash, depression, and dyspepsia, although a potential role in interferon-induced interstitial pneumonitis has not been described. We describe a patient with an excellent clinical response of chronic hepatitis C to combination therapy with IFN-alpha at a dosage of 3 million units per day and ribavirin. The patient developed interstitial pneumonitis that resolved after discontinuation of IFN-alpha and ribavirin. Given that interstitial pneumonitis has previously been reported with high-dose IFN-alpha, this case suggests that this complication may occur with lower dosages of IFN-alpha, although a potential role for ribavirin in this disorder at present remains speculative.
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PMID:Interstitial pneumonitis in a patient treated with alpha-interferon and ribavirin for hepatitis C infection. 1167 22

Hepatocellular carcinoma (HCC) constitutes a difficult health challenge because of its poor prognosis and limited treatment options. Most available therapies are used only for palliation. The use of yttrium-90 microspheres is a new intraarterial therapy consisting of beta-irradiating microspheres measuring 20-30 micro m in diameter that can be delivered directly to the tumors. (90)Y microspheres, which carry the radiation, are selectively taken up by the tumors, thus preserving normal liver. In several studies to date, (90)Y microspheres have proved to have a low toxicity profile and have generally been well tolerated by patients. Other than transient elevation in liver enzyme levels and mild fatigue and fever, no substantial treatment-related toxicities have been observed. Gastrointestinal toxicities occur in a limited number of cases and are preventable with proper knowledge of visceral arterial anatomy. The effect on survival is also promising, with median survival rates of 23 months (95% confidence interval = 14, 44) and 11 months (95% confidence interval = 6, 26) for patients with Okuda stage I and stage II disease, respectively. On the basis of these data, intraarterial delivery of (90)Y microspheres offers a new alternative in the treatment of unresectable HCC.
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PMID:Yttrium-90 microspheres: radiation therapy for unresectable liver cancer. 1235 40

An 80-year-old white woman who presented with fatigue, weakness, weight loss, constipation and polydipsia is reported. The patient was given a diagnosis of severe hypercalcemia and was subsequently found to have clinical, roentgenographic and pathological evidence of hepatocellular carcinoma. Further studies revealed a low parathyroid hormone level, excluding the possibility of primary hyperparathyroidism, and a negative bone survey, precluding metastatic bone disease. The patient's hypercalcemia was believed to emanate from the humoral secretion of a parathyroid hormone-related peptide, which was found to be elevated, and was abated with conservative management while her cancer was being treated with chemotherapy. The details of this rarely documented presentation, which can easily be mistaken for hepatic encephalopathy, are provided.
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PMID:Severe hypercalcemia as an initial presenting manifestation of hepatocellular carcinoma. 1236 13

In this communication, we present results indicating a protein isolated from rat liver mitochondrial intermembrane space that is capable of binding cholesterol and transporting it between the inner and outer mitochondrial membranes. This protein has a molecular weight of 57.5 kDa by SDS-PAGE; however, under native conditions, there is cholesterol-binding capability only as a 115 kDa dimer. Our data show that this dimeric protein may play a role in the regulation of mitochondrial membrane cholesterol levels, a prerequisite for the optimal activity of inner mitochondrial membrane-associated enzyme complexes. In addition, it appears that this protein is largely responsible for the differences in membrane cholesterol levels observed in normal and hepatoma mitochondria, a discrepancy which may help to explain the lack of energy production via oxidative phosphorylation in malignant tumor mitochondria.
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PMID:A cholesterol-binding and transporting protein from rat liver mitochondria. 1248 45


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