Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in 78 Italian patients with hereditary hemochromatosis as well as the relation between HCV antibody (anti-HCV) status, hepatitis B surface antigen (HBsAg) and liver histology. None of the patients had been transfused or ever consumed more than 60 g of alcohol per day. Eighteen showed histological signs of chronic hepatitis, active cirrhosis was present in 12, chronic active hepatitis in 4 and chronic persistent hepatitis in 2. Liver fibrosis or cirrhosis without inflammatory activity was observed in 31 subjects, whereas liver histology was normal except for iron overload in 18. The prevalence of HBsAg in the whole series was 5% and of anti-HCV was 20.5%. The prevalence of HBsAg and anti-HCV was significantly higher in the chronic hepatitis group than in the fibrosis/cirrhosis (p = 0.01) and the normal groups (p < 0.01). Fourteen of 18 hereditary hemochromatosis patients with chronic hepatitis were HBsAg (4) or anti-HCV (10) positive and all the latter subgroup had HCV-RNA in their serum as shown by the polymerase chain reaction. Although most of the patients with associated chronic hepatitis had cirrhosis, their serum ferritin levels and amount of mobilizable iron were significantly lower than those of the fibrosis/cirrhosis group (p < 0.01). This indicates that hepatitis viral infection acts synergistically with iron in accelerating the development of liver damage.
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PMID:Liver damage in Italian patients with hereditary hemochromatosis is highly influenced by hepatitis B and C virus infection. 148 15

Iron overload develops mainly via two mechanisms, by a defect in the regulation of iron absorption (hereditary hemochromatosis) or by parenteral route (chronic red cell transfusion for anemic patients without blood loss) especially in patients with different categories of refractory anemias, and in anemic patients with chronic infection, alcohol excess, and malignancies. The accurate assessment of body iron is indispensable for the correct diagnosis and for finding the optimal treatment schedule for each individual patient. Liver biopsy with quantitative iron determination and histochemistry is still the reference method for the assessment of body iron status for patients with iron overload. New noninvasive measurements (hepatic magnetic susceptibility, CT, and magnetic resonance imaging) are still investigational procedures. It is important to decrease the need for transfusion by judicious use of red cell concentrates, make more widespread use of erythrocytapheresis, determine the red blood cell phenotype of the patient before the onset of a regular transfusion regimen, treat concomitant hepatitis infections, consider splenectomy to diminish red blood cell requirements, and early on consider allogeneic bone marrow transplantation for thalassemic patients who have HLA-identical siblings. It is advisable to screen for the hereditary hemochromatosis gene before starting any kind or regular red blood cell transfusion therapy, and to avoid if possible, the risk of free radical release by transfusional iron overload during the physiologically hypercoagulable state of pregnancy and its effects on the highly proliferative tissues of the fetus.
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PMID:Transfusion-associated iron overload. 935 2

A middle-aged white man of Scotch-Irish ancestry, being treated for chronic hepatitis C, was found to be heterozygous for alpha1-antitrypsin deficiency (PiMZ phenotype) after diagnostic PAS-positive, diastase-resistant globules were detected in a liver biopsy. The globules had not been present in a biopsy obtained 4 yr previously. He was also found to be heterozygous for the cys282tyr mutation of the HFE gene, which is the chief cause of HLA-linked hereditary hemochromatosis (HHC). His liver disease progressed over 4 yr from mild hepatitis to moderate hepatitis with cirrhosis despite therapy with interferon-alpha, and phlebotomy plus interferon. These conditions appeared to have synergistic effects, with the chronic viral hepatitis unmasking the alpha1AT deficiency, and the alpha1AT deficiency (and possibly the heterozygosity for HHC), exacerbating the course of the hepatitis C.
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PMID:Enhanced phenotypic expression of alpha-1-antitrypsin deficiency in an MZ heterozygote with chronic hepatitis C. 973 41

Iron metabolites were measured in liver homogenates and leukocytes of patients with hereditary hemochromatosis (HHC), chronic viral hepatitis, and secondary iron overloading. Iron and ferritin levels in the liver are increased HHC, while in hepatitis only ferritin level is increased. In the leukocytes ferritin concentrations are increased both in HHC and secondary iron loading and less so in viral hepatitis. The leukocytic ferritin level decreased after a course of bleeding sessions and during maintenance therapy for HHC, which can serve as a diagnostically significant sign for evaluating the treatment efficiency.
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PMID:[Indices of iron metabolism in liver homogenates and leukocytes]. 1087 39

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

Porphyria cutanea tarda (PCT) is associated with estrogen, certain medications, alcohol abuse, hepatitis viruses, and iron overload. Numerous studies have demonstrated an increased incidence of hepatitis C in patients with PCT; therefore, hepatitis screening should be routinely performed on these patients. On the other hand, although studies have long suspected hereditary hemochromatosis (HH) to be an underlying condition of PCT, many physicians have a low index of suspicion. Also, diagnosis of HH has been difficult until recently, when the gene mutation was identified. We present a case of a patient with PCT, hepatitis C, and alcoholism who was homozygous for the HH gene mutation.
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PMID:Porphyria cutanea tarda, hepatitis C, alcoholism, and hemochromatosis: a case report and review of the literature. 1507 47

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are strong and independent risk factors for hepatocellular carcinoma (HCC) development. Patients with hereditary hemochromatosis (HH) are considered at risk of developing cancer. However, the interaction between HFE gene mutations and hepatitis viruses for HCC development has not been systematically searched for. To assess the interaction between HFE gene mutations and exogenous risk factors in the risk of HCC occurrence, a case-only approach, in which just a series of patients is enrolled, was used. Three hundred three cirrhotic patients (231 males, 72 females) from five liver units in different geographic areas of Italy, who developed HCC during regular follow-up between January 1999 and March 2003, and whose blood DNA was available, were analyzed. In all subjects, hepatitis B surface antigen (HBsAg), anti-HCV and HFE gene mutations were assayed; alcohol intake was recorded by history. The interaction between HFE genotypes and hepatitis viruses for HCC was estimated by multivariate analysis adjusting for the confounding effect of alcohol intake, area of residence and months of follow-up. Of the 303 HCC cases, 12 (4.0%) were heterozygous for the C282Y mutation, 93 (30.7%) for the H63D, and 198 (65.3%) homozygous for the wild allele. Multivariate analysis showed that C282Y heterozygous males were 3.8-fold (95% CI=1.0-15.2) more likely to be HBV positive and that H63D heterozygous females were 6.0-fold (95% CI=1.2-113.8) more likely to be HCV positive than wild type subjects. In conclusion, given the association between C282Y mutation and HBV infection in male patients with HCC, a careful evaluation and follow-up should be considered in the C282Y-positive subjects with hepatitis B virus related liver disease. The interaction between the H63D mutation and HCV, observed only in women, may reflect a higher sensitivity to H63D-induced iron metabolism abnormalities and a reduced antioxidant capability in the presence of an even minor increase of iron which may occur as a consequence of the coexistence of hepatitis C infection and heterozygosity for HH.
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PMID:Association between heterozygosity for HFE gene mutations and hepatitis viruses in hepatocellular carcinoma. 1589 95

Treatment of virally induced chronic hepatitis consists of interferons, nucleotide and nucleoside analogues. So far, combination therapies are not superior to a monotherapeutic regimen. If detected early, inherited metabolic diseases (e.g. hereditary hemochromatosis, M. Wilson) can be successefuly treated, leading to a normal life expectancy of the patients. In contrary treatment of cholestatic chronic liver disease, especially of PSC, is far from being satisfying, due to our very limited knowledge of the etiology of this diseases. The same holds true for the therapy of NASH. Weight reduction and treatment of the often underlying diabetes are therapeutic cornerstones in the moment. On the other hand, immuosuppression, some times life-long, remains a (highly successful) treatment option in cases of proven autoimmune-hepatitis.
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PMID:[Drug therapy in chronic liver disease]. 1635 88

Epithelial cell adhesion molecule (Ep-CAM) is expressed in a several epithelial tissues and carcinomas, but not on mature hepatocytes. Here, we analysed the expression of Ep-CAM in 230 patients suffering from various liver diseases like chronic hepatitis B and C (HBV and HCV infection), chronic autoimmune hepatitis (AIH), chronic alcoholic liver disease (ALD), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), hereditary hemochromatosis and dysplastic nodules (DNs) as well as hepatocellular carcinomas (HCCs) and cholangiocellular carcinomas (CCCs) by immunohistochemistry. De novo hepatocellular Ep-CAM expression was found in 75.9% of ALD (22/29), 63.6% of HCV (21/33) and 55.6% of each AIH and HBV cases (5/9 and 15/27, respectively). Lower Ep-CAM expression levels were observed for primary sclerosing liver diseases (PBC and PSC) with 25% (3/12) and 7.7% (1/13) of cases. Moreover, only 14.3% of HCCs (9/63) manifested expression, while all CCCs showed strong Ep-CAM expression (5/5). For DNs and hereditary hemochromatosis, Ep-CAM expression was found in 10 and 50% (3/30 and 2/4), respectively. In HBV and HCV, Ep-CAM expression correlated significantly with inflammatory activity as assessed by histological parameters and to the extent of fibrosis. In addition, for HCV also transaminase levels correlated significantly with Ep-CAM expression. Our results indicate that de novo Ep-CAM expression in hepatocytes is frequent in inflammatory liver diseases and is potentially linked to regenerative activity. CCCs and Ep-CAM positive HCCs may represent an attractive target group for Ep-CAM-directed immunotherapies, yet unwanted toxicity may limit the use of such strategies due to Ep-CAM expression in biliary epithelium and several chronic liver diseases such as HBV-and HCV-hepatitis.
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PMID:Expression of epithelial cellular adhesion molecule (Ep-CAM) in chronic (necro-)inflammatory liver diseases and hepatocellular carcinoma. 1636 80

Primary hemochromatosis, alpha-1-antitrypsin (AAT) deficiency, and Wilson's disease are the most common hereditary causes of unclear hepatopathy. Classical primary hemochromatosis (type I) on the basis of a homozygous mutation of the HFE gene, usually presents in adults with increasing hepatocellular siderosis and chronic progressive necroinflammatory liver disease. Homozygous AAT deficiency type PiZZ becomes manifest in newborns as a giant cell hepatitis or findings similar to bile duct atresia, in adults as chronic hepatitis or "cryptogenic cirrhosis". The heterozygous PiZ mutation can lead to PAS-positive hepatocellular AAT deposits increasing over the life time. Immunohistochemical detection of AAT deposits by specific PiZ antibodies is a highly sensitive and specific supplementary method. Molecular analysis of AAT and HFE genes in paraffin-embedded tissue or blood can confirm the diagnosis and allows the zygosity status to be defined. Wilson's disease has to be considered in children and young adults with unexplained histologic findings of chronic hepatitis or steatohepatitis. Rhodanin staining is the most effective histochemical method to detect free copper deposits, but negative staining results do not exclude Wilson's disease. In cases suspected of Wilson's disease further clinical exploration must be initiated. The diagnosis is based on a combination of clinical and biochemical findings, which can be supplemented by mutation analysis of the ATP7B gene.
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PMID:[Hereditary hemochromatosis, alpha-1-antitrypsin deficiency and Wilson's disease. Pathogenesis, clinical findings and pathways to diagnosis]. 1821 Jan 10


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