Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship of pretreatment serum ferritin and hepatic iron concentration to body iron removed by venesections was evaluated in 33 patients with genetic hemochromatosis. The median values of the three variables considered were 1,950 micrograms/L (range = 255 to 10,000), 1,175 micrograms/100 mg dry weight (range = 270 to 4,310) and 10 gm (range = 2 to 41), respectively. At basal liver biopsy 18 patients had cirrhosis, 6 patients had fibrosis and 9 patients had a normal pattern; siderosis was degree 3 in 6 patients and degree 4 in 27 patients. The results of fitting a polynomial regression of second degree showed that the curve of serum ferritin on iron removed was a straight line (R2 = 0.79, with a significant coefficient of linearity, p less than 0.01, and a nonsignificant coefficient of curvature), whereas that of hepatic iron concentration on iron removed showed a curvature (R2 = 0.62, with significant coefficient of linearity and curvature, p less than 0.01) and reached a plateau. The sigmoid model fit the curve of hepatic iron concentration on iron removed (R2 = 0.61), which suggested a saturation of hepatic iron storage capability; the asymptote corresponded to a hepatic iron concentration of about 2,000 micrograms/100 mg. In alcoholic patients (17 cases) the location of the sigmoid was greater than in nonalcoholic patients. Our results suggest that iron deposition occurs in the liver before other organs are involved and that with massive iron overload hepatic deposits reach saturation, after which hepatic iron concentration does not always reflect the amount of total stores. Alcohol consumption could slow the saturation of hepatic iron deposits.
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PMID:Saturability of hepatic iron deposits in genetic hemochromatosis. 139 2

We studied endocrine functions at baseline and after TRH and LHRH stimulation in a group of 7 young male patients with genetic hemochromatosis (HE) without liver damage (i.e. fibrosis and cirrhosis). In five patients endocrine re-evaluations after complete iron depletion was also performed. Mean basal testosterone (T), FSH, LH and PRL were significantly lower than in controls. Serum T increased normally after HCG stimulation. The normal or high increments of LH after LHRH stimulation suggest that secretion capacity of LH was intact and that hypothalamic dysfunction could be responsible for the preclinical gonadal deficiency found in our patients. The response of PRL to TRH indicates that secretion capacity of lactotrophs although present, was decreased and did not improve after phlebotomy therapy. After iron depletion the two patients with the lowest basal T levels showed the highest increments indicating that in the early stages of hypothalamic-pituitary damage gonadal dysfunction is still reversible in HE patients.
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PMID:Preclinical hypogonadism in genetic hemochromatosis in the early stage of the disease: evidence of hypothalamic dysfunction. 140 47

We report a case of neonatal hemochromatosis in which the genetic counseling was initiated by, and based on, retrospective pathologic diagnosis. Perinatal or neonatal hemochromatosis is beginning to be recognized as a distinct clinical entity and one of the most common causes of perinatal cirrhosis. The exact mechanism of liver damage and the relationship to adult type hemochromatosis have not been fully clarified. The pattern of fibrosis in the liver plus the abundant iron deposition in the liver and other organs separate this entity pathologically from other causes of neonatal liver failure. We report on a case of neonatal hemochromatosis that was diagnosed on retrospective autopsy review of an infant with supposed hereditary tyrosinemia, when the family presented for genetic counseling. This case emphasizes to the genetic counselor and pathologist the need to consider the diagnosis prenatally, after birth, or at death, as failure to do so would result in the inability to identify families at genetic risk for neonatal hemochromatosis or in mislabeling a family with another inborn error.
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PMID:Neonatal hemochromatosis: genetic counseling based on retrospective pathologic diagnosis. 144 81

A retrospective study of 127 patients with untreated homozygous genetic hemochromatosis (HGH) was conducted to evaluate the respective roles of iron overload and non-iron-related factors in the development of hepatic fibrosis in HGH. Twenty-seven percent of the patients had cirrhosis, 21% had liver fibrosis and 52% had no fibrosis (prefibrotic group). The mean value of liver iron concentration was increased significantly (p < 0.001) in cirrhotic (378 +/- 144 mumol/g dry wt.) and in fibrotic (331 +/- 168) subjects compared to prefibrotic (237 +/- 108) patients. Of 13 patients with liver iron concentration > or = 500, 12 had liver fibrosis or cirrhosis, versus 48/134 with liver iron concentration < 500. Chronic alcoholic men exhibited hepatic fibrosis or cirrhosis more frequently than non-alcoholic men (p < 0.001). Non-alcoholic men had hepatic fibrosis or cirrhosis more often than non-alcoholic women (p < 0.05). Cirrhotic and fibrotic patients were significantly older than prefibrotic patients whilst a significant correlation between age and liver iron concentration was found in younger patients only. These results suggest that the iron overload threshold necessary to induce fibrosis is modulated by non-iron-related factors such as alcoholism, sex and age. The development of fibrosis in HGH with liver iron concentration < 500 mumol/g is frequent and must lead to a search for associated non-iron-related fibrogenic factors.
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PMID:Liver fibrosis in genetic hemochromatosis. Respective roles of iron and non-iron-related factors in 127 homozygous patients. 148 46

A 56-year-old male patient on chronic hemodialysis developed liver cirrhosis. He received a total of 20 liters of blood transfusion. Bronze pigmentation of the skin and iron deposition to the liver, spleen, pancreas and thyroid gland, which was demonstrated by computed tomography and magnetic resonance imaging studies, and histological demonstration of iron deposition to the thyroid gland, bone marrow and gastric mucosa established a diagnosis of secondary hemochromatosis. Endocrine work-up revealed the presence of diabetes mellitus with minimum insulin secretory response, primary (or thyroprivic) hypothyroidism, hypoparathyroidism and hypogonadotropic hypogonadism. A wide-spread endocrine involvement as seen in this patient is a rare clinical feature of hemochromatosis secondary to massive blood transfusion in hemodialysis patients. Particularly, primary hypothyroidism due to iron deposition to the thyroid gland was quite a rare feature of hemochromatosis.
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PMID:Primary hypothyroidism and multiple endocrine failure in association with hemochromatosis in a long-term hemodialysis patient. 151 78

Evaluation of chronic liver disease begins with a carefully taken history, thorough physical examination, and standard laboratory tests. Often, however, other studies are required, such as a viral hepatitis panel, serologic tests for autoimmune markers, tests for antimitochondrial antibodies, measurement of serum iron and ceruloplasmin levels, liver biopsy, and imaging studies of the extra-hepatic bile ducts. Medical treatment of chronic active hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis remains unsatisfactory. Early treatment of hemochromatosis and Wilson's disease can prevent cirrhosis and liver failure. Liver transplantation is now a viable procedure for patients with end-stage chronic liver disease.
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PMID:Chronic liver disease. The scope of causes and treatments. 158 71

Primary hemochromatosis is a genetically determined autosomal recessive disorder characterized by the excessive accumulation of body iron, most of which is deposited in the parenchymal cells of various organs. alpha 1-Antitrypsin deficiency is characterized among others by defective secretion of alpha 1-antitrypsin from liver cells. Whereas the risk of cirrhosis is increased in homozygous patients (PI ZZ) and possible in heterozygous patients (non-PI MM) as well, a greater risk for hepatocellular carcinoma has been suggested only in homozygous patients. Because these two metabolic disorders are relatively common, it has been difficult to determine whether they are associated with each other. In this study, we tried to determine the relationship between these two disorders using the case material seen at the University of Pittsburgh during a 7-yr period. We studied 15 patients with genetic hemochromatosis. alpha 1-Antitrypsin quantitation and phenotyping were performed in each case using standard methods. The distribution of the various Pi phenotypes was compared with that found in a normal population and reported elsewhere. Odds ratio and chi 2 tests were used to measure the relative risk and significance of association, respectively. Eleven patients (73%) were found to be PI M and four (27%) were identified as being heterozygotes: three (20%) were PI MZ, and one (7%) was PI MS. The prevalence of the PI MS phenotype was similar to that in the general population (7% vs. 6.4%; NS). The PI MZ phenotype, however, was statistically more common in patients with hemochromatosis than in the general population (20% vs. 2.2%; p less than 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association between heterozygous alpha 1-antitrypsin deficiency and genetic hemochromatosis. 835 11

A 58-year-old man, with primary hemochromatosis, cirrhosis, and diabetes mellitus treated with insulin developed hepatoma. As the tumor grew, he lost his dependence on insulin therapy and experienced episodes of hypoglycemia. His response to infuse insulin was studied using the euglycemic clamp technique. Insulin was infused at rates of 1 and 10 mu/kg/min. The insulin dose response curve was shifted to the left and at plasma insulin levels of 72 microU/ml, steady-state glucose consumption was 9.6 mg/kg/min, 50% more than in normals, and nearly three times greater than that in other cirrhotics. The insulin clearance rate was 4417 m1/m2/min, almost five and six times more than in normals and cirrhotics, respectively. Basal hepatic glucose production was 3.6 mg/kg/min, two and three times higher than in normal and in cirrhotic subjects, respectively. The decrease in amino acid during hyperinsulinemia was more than 30% higher than in normal and other cirrhotics. IFG-I and II levels were not elevated in this patient. Increased insulin sensitivity and increased insulin clearance and serum amino acid decrease in response to insulin in vivo, suggest that insulin responsive tissues are at last partially responsible for tumor hypoglycemia. The increased glucose disposal rate probably accounted for the disappearance of the diabetes.
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PMID:Case report: increased insulin sensitivity in tumor hypoglycemia in a diabetic patient: glucose metabolism in tumor hypoglycemia. 165 53

Several data indicate that iron may be involved in the pathogenesis of hepatocellular carcinoma (HCC). A high prevalence of HCC has been reported in patients with genetic hemochromatosis and the risk of HCC appears to be related to the amount and duration of iron overload. Iron, which has been demonstrated to facilitate persistent hepatitis B or C infection, could also act as a co-factor in the pathogenesis of HCC in patients with hepatitis B or C. Among the possible mechanisms by which iron could exert its cancerogenetic potential, free radicals production responsible for heritable genetic alterations appears to be one of the most important, although the fibrogenetic capability of iron, potentially leading to cirrhosis, cannot be underestimated.
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PMID:Iron in the pathogenesis of hepatocellular carcinoma. 166 94

Loss of tumor suppressor genes is involved in the mechanism of tumorigenesis of many solid tumors. We tested 9 hepatitis B virus (HBV)-positive and 10 HBV-negative hepatocellular carcinomas for loss of somatic heterozygosity using 14 polymorphic probes mapping to chromosomes 4, 11, 13, and 17. Losses were found on all chromosome arms tested. The highest frequency of loss was observed at the D13S1 locus (67%) at band 13q12. Losses were also observed at three other loci on 13q. Twenty-one % of informative cases showed loss on 17p using the probe pYNZ22 which maps near the p53 locus. Losses on 4q were infrequent with 17% found at one locus and no loss at two others. The retinoblastoma gene and the locus on 17p were only inactivated in our HBV-negative tumors, although the numbers were too small for statistical significance. For all loci tested, we found no significant differences in the frequency of losses with HBV status, ethnic background, cirrhosis, grade of tumor, or presence of hemochromatosis.
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PMID:Loss of somatic heterozygosity in hepatocellular carcinoma. 167 14


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