[Sinusoidal hepatic fibrosis and diabetes mellitus].
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Adult↗
Biomedical subjects
Y Deugnier
Publications and source records attributed to Y Deugnier.
[A study of lysosomal enzyme activities in serum and leukocytes in chronic hepatic disease (author's transl)].
Five lysosomal enzyme activities (arylsulfatase A, alpha-D-mannosidase, alpha-L-fucosidase, hexosaminidase and beta-D-galactosidase) were determined in serum and leucocytes of 30 controls and 114 patients suffering from various liver diseases, including 30 with idiopathic hemochromatosis and 34 with alcoholic cirrhosis. The results show (1) a decrease of the serum arylsulfatase A activity in idiopathic hemochromatosis, (2) an increase of this activity in cholestatic jaundice, and (3) mainly, a sharp rise of the leucocyte lysosomal enzyme activities in the liver diseases studied (chiefly idiopathic hemochromatosis and alcoholic cirrhosis). The mechanism and the meaning of these disturbances are discussed.
Adult↗
Perhexiline maleate toxicity on human liver cell lines.
When added to the culture medium of human liver cell lines, perhexiline maleate induced formation of numerous myeloid bodies containing unicentric or multicentric smooth membranes within a few days. The nine lysosomal enzyme activities studied, except for beta-galactosidase which decreased, remained unchanged. These results indicate that on cultured human liver cells perhexiline maleate has an effect similar to that described on hepatocytes of some patients treated with this drug and suggest that myeloid body formation is not due to impairment of lysosomal enzyme activities.
Adult↗
Ascorbic acid status in idiopathic hemochromatosis.
Vitamin C status was studied, by means of leucocyte ascorbic acid concentrations, in 67 cases of idiopathic hemochromatosis subdivided into 44 untreated and 25 treated cases (2 patients belonging to both subgroups) and compared to 31 normal subjects and 37 alcoholic cirrhosis patients. The control groups exhibited the following mean levels (+/- SEM): 34.4 +/- 1.9 microgram/10(8) WBC in normals and 22.0 +/- 1.8 microgram/10(8) WBC in alcoholic cirrhosis. In idiopathic hemochromatosis the mean levels were: for the untreated group 19.5 +/- 1.7 microgram/10(8) WBC and for the treated group 34.3 +/- 2.3 microgram/10(8) WBC. These results (1) affirm an important vitamin C deficiency in the untreated disease; (2) suggest that iron overload is the main causal factor in view of the striking difference--to date unreported--between untreated and treated cases of idiopathic hemochromatosis. Besides its possible theoretical interests, this vitamin C deficiency is responsible in idiopathic hemochromatosis for a significant underestimation of the desferrioxamine-induced urinary iron excretion.
Adult↗
[Malarial hepatitis. Apropos of a case].
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Adult↗
Serum alpha-L-fucosidase: a new marker for the diagnosis of primary hepatic carcinoma?
alpha-L-fucosidase, a lysosomal enzyme which catabolizes fucoproteins, was studied in sera from 30 controls, 32 patients with primary hepatic carcinomas, 24 patients with secondary metastatic liver carcinomas and 36 patients with cirrhosis. Serum alpha-L-fucosidase was increased in primary hepatic carcinomas (145.5 +/- 12 nkat per liter) with a high statistical significance versus controls (51.4 +/- 4.5 - p less than 10(-7], secondary metastatic liver carcinomas (58.9 +/- 6.4 - p less than 10(-5] and cirrhotics (71.3 +/- 6 - p less than 10(-5). A level exceeding 110 was a useful marker for the diagnosis of primary hepatic carcinoma with 75% sensitivity and 90% specificity.
Adenocarcinoma↗
Cell types involved in collagen and fibronectin production in normal and fibrotic human liver.
Three collagen types (I, III and IV) and fibronectin were localized in normal and alcoholic human liver by light and electron microscopy using the indirect immunoperoxidase technique. In normal liver, most of the bundles of collagen fibers stained for type pro-III collagen while only a few reacted for type I. Basement membranes stained for type IV collagen which formed discontinuous discrete deposits in sinusoids. Only fibronectin appeared as an almost continuous layer in the space of Disse. At the intracellular level, hepatocytes were found to contain little type I collagen and large amounts of fibronectin. Fat-storing cells strongly stained for type IV collagen and expressed low amounts of types I and III collagen and fibronectin. Endothelial cells contained low amounts of all the components. Alcoholic livers were studied at three stages: steatosis, fibrosis and cirrhosis. Qualitative and quantitative differences were observed in extracellular and intracellular distributions of matrix proteins. Increased amounts of all components were usually found in fibrotic and cirrhotic livers compared to normal liver. In two fibrotic livers which contained numerous bundles of collagen in the sinusoids, fat-storing cells stained more intensely for type III collagen. In a cryptogenic fibrotic liver, abundant type IV collagen was observed in hepatocytes. These results suggest that hepatocytes, fat-storing cells and endothelial cells are engaged in production of extracellular matrix components in normal human liver. In fibrosis, hepatocytes which normally did not synthesize types III and IV collagen may produce these collagens.
Adolescent↗
Serum hyaluronate in liver diseases: study by enzymoimmunological assay.
It has been suggested that glycosaminoglycans are involved in the pathogenesis of liver fibrosis. Furthermore, recent studies have reported that one of them, hyaluronate, was mainly taken up and degraded by the liver. Using an enzymoimmunological assay, based on hyaluronate-hyaluronectin interaction, serum levels of hyaluronate were measured in 113 patients with various liver diseases. Patients were divided into six groups according to clinical, biological and histological data: Group 1-alcoholic cirrhosis (n = 47) including alcoholic cirrhosis with alcoholic hepatitis (n = 24); Group 2-primary biliary cirrhosis (n = 21); Group 3-cirrhosis related to viral hepatitis (n = 10); Group 4-idiopathic hemochromatosis (n = 17); Group 5-alcoholic fatty liver (n = 8); and Group 6-viral or drug acute hepatitis (n = 10). Ninety-four blood donors were studied as controls. Levels of hyaluronate were found to be strikingly elevated in Group 1 (1,225 +/- 1,137 micrograms per liter), Group 2 (792 +/- 739 micrograms per liter), Group 3 (649 +/- 373 micrograms per liter), and Group 4 (246 +/- 242 micrograms per liter), whereas patients in Group 5 (94 +/- 63 micrograms per liter) and Group 6 (73 +/- 57 micrograms per liter) had values close to controls (23 +/- 17 micrograms per liter). There was a significant correlation between serum hyaluronate and serum albumin, prothrombin time, factor V concentration and serum gamma-globulins. It is suggested that hyaluronate levels reflect both active fibrosis and hepatic failure and may be a quantitative marker of severity of hepatic injury.
Adult↗
Low penetrant hemochromatosis phenotype in eight families: no evidence of modifiers in the MHC region.
The gene responsible for hemochromatosis (HFE) has been identified on the short arm of chromosome 6, 4.5 Mb telomeric to HLA-A. A major mutation C282Y is closely correlated with the disease, as it accounts for 68 to 100\% of the cases of hemochromatosis. Nevertheless, some C282Y homozygotes subjects have no clinical or biological expression of the disease. Moreover, in Northern European populations a large discrepancy is observed between the number of C282Y homozygotes and the number of diagnosed hemochromatosis patients, suggesting incomplete penetrance of the mutation. To localize and identify the modifying genes, we investigated eight families including C282Y homozygous relatives showing no clinical signs of the disease, in addition to the hemochromatosis patients. Genomic DNA from 20 C282Y homozygotes (10 patients and 10 siblings presenting no or minor biological abnormalities) were studied. Five polymorphisms from the HFE gene were determined by PCR restriction. Extended haplotypes of the 6p21.3 region were constructed with 10 microsatellite markers. All the C282Y homozygotes shared the same HFE polymorphism. The haplotypes presented no significant difference between the probands and their unaffected relatives. These studies suggest that neither HFE polymorphism nor genes surrounding HFE are able to modulate HFE expression.
Adult↗
Superparamagnetic iron oxide: clinical time-response study.
Superparamagnetic iron oxide (AMI 25) is a promising new contrast agent for imaging the reticuloendothelial-system. Iron oxide crystals possess a large magnetic susceptibility and enhance proton relaxation rates, especially transverse relaxation (T2). In order to guide the clinical utilization of this contrast media we analyzed 4 patients with malignant lesions of the liver before and after slow intravenous administration (20 mumol Fe/kg) of AMI 25. We performed two magnetic resonance (MR) sequences at different times using a 0.35 T magnet. MR signal-to-noise ratio (SNR) of the reticuloendothelial system (particularly the liver SNR) decrease promptly. The maximum decrease in SNR (67-72% for the liver, 46-65% for the spleen, 23-41% for the bone marrow) is observed 3 h after injection (P less than 0.01). However, except the peak of contrast enhancement in T1-weighted sequences of splenic tissue, the curve describes a plateau within 30 min and 6 h, allowing a delay between injection and imaging. T2-weighted sequences give a greater contrast-to-noise ratio (CNR) by adding the spontaneous tumor contrast to the effect yielded by AMI 25. These results suggest that images must be acquired between 1 and 6 h after intravenous administration of superparamagnetic iron oxide.
Aged↗
[Disulone and hepatosiderosis].
BACKGROUND: Disulone (dapsone + iron oxalate) is a sulfone used in the treatment of numerous skin diseases. We report two cases of hepatosiderosis secondary to long-term administration of Disulone. PATIENTS AND METHODS: Case n degrees 1. A 51-year-old man was treated with Disulone for a neutrophilic skin disease. After 17 years of treatment, elevated serum ferritin and free iron with hemolysis were found. Liver biopsy confirmed hepatosiderosis. A diagnosis of genetic hemochromatosis was ruled out by the absence of C282Y mutation of the HFE gene. Case n degrees 2. A 52-year-old man receiving Disulone for dermatitis herpetiformis for 25 years presented elevated serum ferritin and free iron with hemolysis. Hepatic iron overload was confirmed by liver biopsy. The absence of C282Y mutation (HFE gene) ruled out a diagnosis of genetic hemochromatosis. DISCUSSION: In our two cases, hepatosiderosis was noted after long-term administration of Disulone. This complication has been reported only rarely. In murine models, a relationship was found between prolonged administration of dapsone and hepatic iron overload as revealed by hemolysis. Although it is difficult to extrapolate this relationship to humans with any certainty, our patients had also chronic hemolysis and iron overload secondary to administration of Disulone. Moreover in France, dapsone is marketed in combination with iron oxalate, with the attendant risk of iron overload. These cases raise the question of the need for serum ferritin analysis during Disulone therapy.
Anti-Inflammatory Agents, Non-Steroidal↗
Interferon and ursodeoxycholic acid combined therapy in chronic viral C hepatitis: controlled randomized trial in 203 patients.
AIMS: This prospective randomized trial was carried out in order to determine whether the long-term administration of ursodeoxycholic acid after discontinuation of interferon had any beneficial effect on the clinical course of hepatitis C virus infection. METHODS: Enrolled in the study were 203 patients with chronic active hepatitis C. They were all given: interferon alpha-2a (3 MU subcutaneously thrice a week) and ursodeoxycholic acid (10 mg/kg/day) for 9 months. At month 9, biochemical responders only were randomized into ursodeoxycholic acid treatment or placebo for 12 additional months (double blind study). RESULTS: At the end of interferon therapy, 71 patients (37%) were virological responders and 107 (56%) patients were biochemical responders and were randomized: 54 into the ursodeoxycholic acid group and 53 into the placebo group. Sustained response was evaluated 12 months after withdrawal of interferon. Sustained biochemical and virological responses were, respectively, 30% and 22% in the ursodeoxycholic acid group and 46% and 32% in the placebo group, which did not significantly differ. Histological evolution of fibrosis and necrotic inflammatory activity were similar in the two groups. CONCLUSION: Continuation of ursodeoxycholic acid therapy after withdrawal of interferon in patients with end-of-treatment response did not result in any significant improvement either in the maintenance of response to interferon or in liver histology.
Adolescent↗
Haemochromatosis and HFE gene.
The discovery of the HFE gene has improved classification and diagnosis of iron overload. Most patients with a phenotypic diagnosis of haemochromatosis are homozygote for the C282Y mutation. Among those with other genotypes, only compound heterozygotes, who present the C282Y mutation on one chromosome and the H63D on the other, may present with haemochromatosis, but with a low penetrance and a mild expression. Other patients usually present with another cause of iron overload, such as insulin resistance, alcoholic liver disease or liver cirrhosis. The practical management of haemochromatosis has been greatly modified, since liver biopsy is no more necessary for diagnosis in C282Y homozygotes, and is only needed for exclusion of cirrhosis. Family screening has also greatly benefited from genotyping.
Chromosome Mapping↗
[Recommended algorithms of prescription in the diagnosis of iron deficiency and overload].
In view of the recent development of new tests of biochemistry and molecular biology the assessment of iron status should be reconsidered and updated. The French Society of Clinical Biology (SFBC) and the French Society of Hematology (Cellular Hematology Group) recommend algorithms in the diagnosis of iron deficiency and iron overload bearing in mind the best efficiency and health economy. These recommendations are based on the known sensibility and specificity of each test. The analytical requirements for the determination of the tests as well as the clinical and biological signs evoking an iron deficiency or overload are recalled.
Adult↗
[Association of sarcoidosis and primary biliary cirrhosis: review of the literature apropos of a new case].
We report a case of sarcoidosis associated with primary biliary cirrhosis in a 56-year old woman, with a 5 years' follow up. Sarcoidosis was ascertained by chest X ray, gallium scintigraphy, broncho-alveolar washing and liver biopsy (intralobular epithelioid granulomas). The diagnosis of primary biliary cirrhosis was based on IgM level increase (4 g/l), AMA positivity (1/1000) and liver biopsy assessment (non suppurative chronic cholangitis). Such an association is rare (12 detailed cases in literature), brings out pathophysiological questions and points to an additional mechanism of cholestasis in patients with sarcoidosis.
Female↗
[The value of computerized tomography in the assessment of hepatic iron overload in genetic hemochromatosis].
The aim of the present study was to evaluate the effectiveness of single-energy computed tomography in determining iron overload in idiopathic hemochromatosis, with special reference to slightly overloaded cases. Liver attenuation was determined in 100 patients (46 cases of idiopathic hemochromatosis, 32 cases of chronic liver disease, and 22 normal controls). The iron load was determined for the first two groups by biochemical determination of liver iron concentration (performed in all but 12 subjects in the chronic liver disease group) and hepatic histologic grading. The main results for liver attenuation (upper normal limit, 72 Hounsfield units) showed that despite a high specificity (0.96), this parameter was of low sensitivity (0.63). Although mean liver attenuation in idiopathic hemochromatosis (77 +/- 14) was significantly higher than in chronic liver diseases (53 +/- 17; p less than 10(-4], and normal controls (66 +/- 3; p less than 10(-3], and despite an overall good correlation between liver attenuation and liver iron concentration (r = 0.72; p less than 10(-3], liver attenuation was unable to detect moderate iron overload. Fourteen of 18 patients with a liver iron concentration of less than 150 mumol/g dry liver wt had liver attenuation values of less than 72. Moreover, 3 of 18 subjects with a liver iron concentration of greater than 150 had a liver attenuation of less than 72. Of these 17 false-negatives, only 7 could be attributed to associated steatosis. On the whole, single-energy computed tomography, when used on a routine basis for diagnosing iron overload, is of limited clinical value in idiopathic hemochromatosis due to its poor sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Sinusoid dilatation and the use of oral contraceptives. Apropos of a case with a review of the literature].
We are reporting the case of a 23 year-old woman who developed an acute painful syndrome of the right hypochondrium with hepatic cytolysis while taking oral estro-progesterone medications. The liver biopsy showed a sinusoid dilatation. The course was favorable after discontinuation of oral contraceptives.
Adult↗
[Idiopathic hemochromatosis in 1984].
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Hemochromatosis↗