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Biomedical subjects

Y Deugnier

Publications and source records attributed to Y Deugnier.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Epidemiology of hepatitis C virus infection in 1,304 HCV positive patients: variations according to the origin of transmission and year of diagnosis].

UNLABELLED: The evolution of epidemiological data on hepatitis C virus infection is poorly documented and thus the impact of screening is difficult to evaluate. AIM: To study epidemiological variations based on the origin of transmission and the year of diagnosis of hepatitis C virus infection. METHODS: The files of all 1304 patients seen in the hepatology unit of the Rennes University Hospital were analyzed (retrospectively before and prospectively after October 1995) in relation to epidemiological features. RESULTS: Despite widespread screening which is the source of 60% of the diagnoses, the total number of new cases of hepatitis C infection per year has not increased. Compared to patients diagnosed in the first years following the discovery of the virus, patients recently identified were younger (42 +/- 14 years) and frequently drug addicts (40%). Aminotransaminases were normal in 20% of cases. The frequency of cirrhosis has declined (17%). There has been a decrease in the proportion of patients who undergo liver biopsy (50%) and treatment with interferon (one third of patients). CONCLUSIONS: The impact of screening on the number of newly treated patients seems to be lower than previously predicted.

Adult↗
PubMed1998

Evaluation and interpretation of iron in the liver.

Faced with hepatic siderosis, the pathologist must (1) determine the parenchymal, mesenchymal, or mixed type of iron overload; (2) quantify liver iron by either histology or biochemistry; (3) seek for associated iron-related lesions, especially sideronecrosis, fibrosis, and iron-free-foci; and (4) assess any other liver damage. The discovery of the HFE gene has modified the management of hemochromatosis. Because homozygosity for the C282Y mutation is diagnostic of the condition regardless of the liver iron concentration-to-age ratio, indication for liver biopsy in C282Y homozygotes is restricted to the assessment of prognostic lesions, such as fibrosis and iron-free-foci. In patients with a phenotype compatible with hemochromatosis but nonhomozygous for the C282Y mutation, liver biopsy remains mandatory to assess nonhemochromatosis causes of iron overload (rare hereditary defects of iron metabolism and transport and iron overload secondary to polymetabolic syndrome, to porphyria cutanea tarda, or to cirrhosis). The evaluation of iron distribution within liver cells and throughout lobules and the assessment of associated lesions are the most important features that allow for correct classification of nonhemochromatosis iron-overload syndromes.

Hemochromatosis↗
PubMed1998

Prevalence of the C282Y mutation in Brittany: penetrance of genetic hemochromatosis?

Hemochromatosis (GH) is an inborn error of iron metabolism, characterized by progressive iron loading that, if untreated, causes high morbidity and death. The gene responsible for the disease (HFE), located 4.5 megabases telomeric to the HLA-A locus, encodes a protein homologous to class I MHC molecules. A main mutation, C282Y, has been identified within the gene. Although hemochromatosis is considered as the most frequent inherited disease in the populations of Northern European origin, its prevalence in Brittany had not been evaluated yet. In this issue we report the C282Y mutation frequency in a cohort of 1000 newborns from maternity hospitals of the four breton départements. The homozygote frequency was 5/1000 and heterozygote frequency was 12%; such high frequencies raise the question of the penetrance of the disease and the relevance of systematic genotypic screening for hemochromatosis.

Alleles↗
PubMed1997

Clinical features of genetic hemochromatosis in women compared with men.

BACKGROUND: The clinical expression of hemochromatosis is presumed to be less frequent and less severe in women than in men because of the iron loss associated with menses and pregnancy, but this hypothesis has not been validated. OBJECTIVE: To compare the clinical features of women who have genetic hemochromatosis with those of men who have the disease. DESIGN: Cross-sectional study. SETTING: Tertiary referral centers for hemochromatosis in France and Canada. PATIENTS: 176 women and 176 men with hemochromatosis, matched for year of birth. MEASUREMENTS: Age at presentation, clinical symptoms, transferrin saturation, serum ferritin level, hepatic iron concentration, and hepatic iron index. RESULTS: Hepatic iron concentration and hepatic iron index were similar in men and women. Women had lower serum ferritin levels than men did (911 micrograms/L compared with 1911 micrograms/L; mean difference, 1000 micrograms/L [95% CI, 669 micrograms/L to 1331 micrograms/L]) and less iron removed by venesections (5.5 g and 8.6 g; mean difference, 3.1 g [CI, 1.5 g to 4.8 g]). Compared with women, men had a higher incidence of cirrhosis (25.6% and 13.8%; mean difference, 11.8 percentage points [CI, 3.2 to 20.4 percentage points]) and diabetes (15.9% and 7.4%; mean difference, 8.5 percentage points [CI, 1.9 to 5.2 percentage points]). Compared with men, women had a higher incidence of fatigue (64.8% and 42%; mean difference, -22.8 percentage points [CI, -32.9 to -12.5 percentage points]) and pigmentation (48% and 44.9%; mean difference, -13.1 percentage points [CI, -23.4 to 2.7 percentage points]). Hepatic iron concentration and hepatic iron index were greater in women in whom menstruation had stopped before 50 years of age. Serum ferritin levels and transferrin saturation were normal in 6.2% of women and 0% of men. CONCLUSIONS: Women with genetic hemochromatosis can have full phenotypic expression of the disease, including cirrhosis. Recognizing the nonspecific nature of presenting symptoms in women is essential for early diagnosis and treatment.

Age Factors↗
PubMed1997

[Hepatic fibrogenesis].

The hepatic extracellular matrix is involved in both the stability of liver architecture and the hepatic function. Fibrogenesis occurs during various chronic liver diseases. It is the consequence of an imbalance between synthesis, deposition and degradation of extracellular matrix components leading to fibrosis and, then, cirrhosis. Hepatic stellate cells are the main source of extracellular matrix components in fibrogenesis. Among the factors involved in fibrogenesis, transforming growth factor beta 1 plays a central role. The vascular and cellular consequences of liver fibrogenesis require new specific diagnostic and therapeutic strategies.

Extracellular Matrix↗
PubMed1997

A new syndrome of liver iron overload with normal transferrin saturation.

BACKGROUND: We investigated patients who had unexplained hepatic iron overload and normal transferrin saturation. METHODS: 65 patients with a median liver iron concentration of 65 mumol/g dry weight of liver (normal < 36 mumol/g), hyperferritinaemia (566 micrograms/L; normal < 400 micrograms/L), and normal transferrin saturations (32%) were compared with genetic haemochromatosis (GH) controls including homozygous (matched for sex and serum ferritin concentration) and heterozygous individuals. Relatives of patients who had ratios of liver iron concentration to age greater than 1.9 were also studied. FINDINGS: The 65 patients were significantly older and had significantly less hepatic iron overload than individuals with genetic haemochromatosis. The frequency of HLA-A3 antigen was significantly lower in these patients than in individuals with homozygous (p < 0.0001) or heterozygous (p < 0.0002) GH. Five HLA-identical siblings of the patients had normal serum ferritin concentrations. Most of the patients (95%) had one or more of the following conditions; obesity, hyperlipidaemia, abnormal glucose metabolism, or hypertension. INTERPRETATION: We have found a new non-HLA-linked iron-overload syndrome which suggests a link between iron excess and metabolic disorders. The current diagnostic criteria for genetic haemochromatosis should be reviewed.

Adolescent↗
PubMed1997

The relationship between iron overload, clinical symptoms, and age in 410 patients with genetic hemochromatosis.

The aim of this study was to investigate the relationship between iron overload, age, and clinical symptoms in genetic hemochromatosis. The relationship was studied between clinical symptoms and liver iron concentration, serum ferritin, and iron removed in a retrospective study of 410 homozygotes diagnosed using strict criteria. No significant relationship was found between liver iron concentration, iron removed by venesection, and serum ferritin level with age. The prevalence of cirrhosis, diabetes, cardiac disease, pigmentation, and fatigue increased as liver iron concentration increased. The most common presentations at diagnosis were fatigue or as an incidental finding in all age groups. Twenty-seven percent of patients (110 of 410) had no clinical symptoms of hemochromatosis. Iron accumulation is highly variable in patients with genetic hemochromatosis. The significant relationship between liver iron concentration and cirrhosis, diabetes, cardiac disease, pigmentation, and fatigue confirms the importance of iron toxicity in the pathogenesis of hepatic and extrahepatic disease. The nonspecific nature of the presenting features in patients and the presence of significant clinical symptoms in patients discovered through family investigations underscore the importance of family and population screening for hemochromatosis.

Adolescent↗
PubMed1997

Ultrastructural sequences during liver iron overload in genetic hemochromatosis.

BACKGROUND/AIMS: The pathway through which iron contributes to liver cell damage and cirrhosis in genetic hemochromatosis is not clear. The objective of the present study was to describe the ultrastructural changes in liver biopsies of patients in various stages of this condition and to correlate these with clinical, histopathological and biochemical data. METHODS: Liver biopsies from 20 patients with genetic hemochromatosis were examined by transmission electron microscopy. The use of unstained thin (60 nm) sections facilitated the identification and localization of the electron-opaque compounds ferritin and hemosiderin in various liver cells. Stained thin sections permitted evaluation of the concomitant subcellular damage and collagen deposition. The ultrastructural observations were corroborated with the histopathological findings and biochemical data. RESULTS: All patients had liver iron overload, which was classified as mild, moderate or severe. In the stage of mild overload (hepatic iron concentration HIC 93.5+/-23.3 micromol/g and hepatic iron index HII 2.3+/-0.7), cytosolic ferritin and scarce pericanalicular lysosomes (siderosomes) were seen in periportal hepatocytes (acinar zone 1), without evidence of organelle damage, and in the absence of sinusoidal cell siderosis. In moderate overload (HIC 190.8+/-41.5 micromol/g and HII 4.3+/-1.9), ferritin was identified in hepatocytes of all acinar zones, and the pericanalicular siderosomes were abundant, especially in acinar zone 1. Single hepatocytes showed organelle damage and occasional sinusoidal cells showed siderosis. In severe overload (HIC 308+/-49.0 micromol/g and HII 7.5+/-1.7), hepatocytes of all acinar zones were filled with large, hemosiderin-containing siderosomes, and changes in mitochondria, smooth and rough endoplasmic reticulum and nuclei were conspicuous. Marked sinusoidal cell siderosis and collagen deposition were observed predominantly in this stage. CONCLUSIONS: Electron microscopy has shown that during the long, latent stage of "compensated" genetic hemochromatosis, hepatocytes display only minimal subcellular changes, other than iron overload. "Decompensated" overload, characterized by extensive subcellular pathology and focal necrosis, is reached when 1) the hepatocytic siderosis is generalized (i.e. beyond pericanalicular polarization of siderosomes in hepatocytes, and beyond zone 1 in the acinus); and 2) there is evidence of massive siderosis of sinusoidal cells. These findings support the concept of a critical level of hepatic iron concentration beyond which organelle damage is conspicuous and liver cell injury may become irreversible.

Adult↗
PubMed1997

A reappraisal of hepatic siderosis in patients with end-stage cirrhosis: practical implications for the diagnosis of hemochromatosis.

The aim of this study was to describe the histologic pattern of iron distribution in end-stage cirrhosis due to various causes and to test the reliability of the hepatic iron index (equal to hepatic iron concentration divided by age) in excluding or confirming associated hemochromatosis in such a condition. Large slices of the resected livers of 30 patients transplanted for alcoholic and/or viral end-stage cirrhosis were assessed histologically for iron distribution and biochemically for hepatic iron concentration in the least and the most iron-overloaded nodules of each case. HLA-A3 was used as the marker for the hemochromatosis gene in the population studied. Intranodular parenchymal siderosis was found in 23 cases (12 spotty, 11 diffuse) with diffuse intrabiliary iron deposits apparent in only two cases. Although in 14 patients the hepatic iron index was significantly high (> 1.9) so as to suggest hemochromatosis, these cases did not correspond to homozygous hemochromatosis with respect to the prevalence of HLA-A3 antigen. End-stage cirrhosis arising from different causes is frequently complicated by parenchymal siderosis that may mimic hemochromatosis, including a hepatic iron index greater than 1.9. The diagnosis of hemochromatosis in patients with end-stage cirrhosis, even those with a hepatic iron index greater than 1.9, should rely mainly on clinical and histologic data.

Adult↗
PubMed1997

Effect of ursodeoxycholic acid on liver iron stores and distribution in rats with normal or iron-supplemented diet.

Iron excess is a potential liver-damaging factor, and bile salts can increase iron digestive absorption and iron biliary excretion. The aim of this study was to investigate in rats the effect of ursodeoxycholic acid, a bile salt used in the treatment of chronic liver disease, on the hepatic iron stores in normal and iron-overload conditions. UDCA was administered by gavage to Sprague-Dawley rats. Iron hyperabsorption and overload were obtained by 5% carbonyl iron addition in diet. Hepatic iron stores and distribution were evaluated by liver iron concentration measurement and histologic assessment, respectively. Whatever the iron content of the diet, liver iron concentration was not modified by UDCA administration compared with the control groups. Iron distribution was not modified by UDCA in rats with normal diet. The total iron score was only transiently lowered by UDCA in iron supplemented rats compared with the control group at 1 month. In conclusion, chronic UDCA administration does not modify liver iron stores and distribution in rats with both normal or increased digestive iron absorption. These data suggest that UDCA is unlikely to increase hepatic iron stores in treated patients and that the benefit of UDCA treatment is probably not related to a decreasing effect of liver iron content.

Animals↗
PubMed1997

Liver iron concentration and distribution in chronic hepatitis C before and after interferon treatment.

BACKGROUND: Recent studies have suggested that, in patients with chronic hepatitis C, elevated iron stores are predictive of a poor response to interferon. AIMS: To assess liver iron concentration and distribution before and after interferon treatment in patients with hepatitis C in order to evaluate further the role of iron in the pathogenesis of hepatitis C. PATIENTS: Fifty-five patients with hepatitis C treated with alpha interferon for six months. METHODS: Patients were evaluated for liver iron concentration (normal value < 36 mumol/g), and liver iron distribution before and six months after therapy. RESULTS: At entry: liver iron concentration was elevated in 16/55 patients (29%); iron staining (Perls' staining) was found in 31/55 patients (56%) mainly within Kupffer and endothelial cells. Iron load was significantly higher in patients with the most histological inflammatory activity. Following treatment: liver iron concentration decreased significantly (40 (24) to 30 (17) mumol/g, p = 0.001); this was related to iron depletion in mesenchymal cells. Iron depletion occurred regardless of the response to therapy. Elevated liver iron concentration was not found to be a predictive factor of failure of interferon. CONCLUSION: Although liver iron stores were usually normal or only slightly elevated in patients with chronic hepatitis C, biochemical and histological liver iron content decreased following treatment due to the diminution in mesenchymal iron deposits. Iron depletion was interpreted as both a consequence of the anti-inflammatory effect of treatment and a factor of improvement in liver histology.

Adult↗
PubMed1997

[Histologic quantification of hemochromatotic and non-hemochromatotic liver siderosis. A stidu of 254 liver biopsies].

Non hemochromatotic liver siderosis often present an heterogeneous iron distribution, but histological scoring of iron overload are validated only in case of genetic hemochromatosis, where iron is homogeneously distributed. The aim of this work was to study the improvement of histological scoring by introducing a coefficient of heterogeneity in cases of heterogeneous liver siderosis. Thus, on 254 liver biopsies with siderosis were determined: i) the histologic total iron score (TIS) as previously described; ii) the coefficient of heterogeneity, leading to corrected TIS (corTIS); iii) the liver iron content (LIC). Liver siderosis was homogeneously distributed in 160 biopsies and heterogeneously distributed in 94. Correlation between histological scoring and LIC, in the group with heterogeneous liver siderosis, was improved by the use of the coefficient of heterogeneity. This coefficient leads to accurately quantify all liver siderosis.

Adult↗