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Yves Deugnier

Publications and source records attributed to Yves Deugnier.

At least 19 recordsLinked to original sources
PubMed2006

Liver iron is a surrogate marker of severe fibrosis in chronic hepatitis C.

BACKGROUND/AIMS: Patients with chronic hepatitis C have frequently mild to moderate liver iron overload which increases with fibrosis stage. Thus, it has been postulated that iron could enhance the progression of fibrosis. However, the real impact of iron is still controversial. The study was undertaken to determine the effect of confounding variables. All factors known to influence both iron overload and fibrosis were taken into account. METHODS: Five hundred and eighty-six patients, who had liver biopsy performed prior to antiviral treatment, were included. Serum ferritin and liver iron were correlated with clinical, biological and histological variables in univariate and multivariate analysis. The impact of iron on fibrosis was evaluated in multivariate analysis in the whole group and in the subgroup of 380 patients with available date of infection. RESULTS: Hyperferritinemia, encountered in 27%, was associated with liver iron deposits in only 46% of cases. Liver iron was elevated in 17%, and correlated with age, male sex, and alcohol intake. The univariate strong link which existed between liver iron and fibrosis disappeared after adjustment for confounding variables. CONCLUSIONS: According to the results of this study, liver iron should be considered more as a surrogate marker for disease severity than as a fibrogenic factor per se.

Adult↗
PubMed2006

Reversibility of hepatic fibrosis in treated genetic hemochromatosis: a study of 36 cases.

The current study was undertaken to assess whether fibrosis could regress under venesection therapy in patients with C282Y homozygous genetic hemochromatosis. The 36 patients studied were recruited from a subfile of our database consisting of 125 C282Y homozygotes with either severe fibrosis or cirrhosis (F3 or F4 fibrosis stage, respectively, according to the METAVIR grading system). The second liver biopsy was performed for management of liver cancer, extrahepatic surgery, or assessment of liver fibrosis. All paired biopsies were reviewed by two pathologists without knowledge of clinical data. Among the 13 patients who had F3 fibrosis on their initial liver biopsy, 3 had F0, 6 had F1, and 2 had F2 on their second liver biopsy. Among the 23 patients with cirrhosis on their initial liver biopsy, 1 had F0, 4 had F1, 3 had F2, and 2 had F3 on their second liver biopsy. When defining regression of fibrosis as a decrease of at least 2 METAVIR units, fibrosis regressed in 9 of 13 (69%) F3 and in 8 of 23 (35%) F4. When the ratio of gammaglobulins (g/L) to (platelets [n/mm(3)] x prothrombin activity [%]) was greater than 7.5, fibrosis never regressed. In conclusion, these data extend the concept of regression of fibrosis to patients with treated genetic hemochromatosis and suggest that some simple biochemical tests would be predictive of further regression of fibrosis as a result of venesection therapy. If confirmed on larger series, this could modify the ultrasound screening policy of hepatocellular carcinoma in genetic hemochromatosis.

Adolescent↗
PubMed2005

Phenotypic expression in detected C282Y homozygous women depends on body mass index.

BACKGROUND/AIMS: In HFE-related haemochromatosis, a large proportion of C282Y homozygotes, especially women, are not detected by phenotypic screening using transferrin saturation. The aim of this study was to identify the clinical and biochemical factors associated with non-expression of the disease as defined as transferrin saturation <45%. METHODS: The study was performed in 78 (57 women and 21 men) C282Y homozygotes identified through a large-scale screening program conducted on 19,644 French subjects. Biometric, clinical and biochemical variables including those susceptible to influence body iron stores were tested for association with transferrin saturation levels <45%. RESULTS: Non-expression was observed in 26/57 (46%) women and in 5/21 (24%) men. At multivariate analysis, female gender (OR: 16.5, 95%CI 1.8-146.5; P = 0.012), body mass index (OR: 1.21, 95%CI 1.02-1.44; P = 0.027), haemoglobin levels (OR: 0.88, 95%CI 0.81-0.97; P = 0.012) and serum ferritin levels (OR: 0.99, 95%CI 0.98-1.00; P = 0.007) were significantly and independently associated with a non-expressing phenotype. CONCLUSIONS: Excess body mass is commonly associated with the lack of phenotypic expression in detected C282Y homozygotes. This should be kept in mind with respect to the design and cost-effectiveness of phenotypic screening programs for haemochromatosis.

Adult↗
PubMed2005

Redox active plasma iron in C282Y/C282Y hemochromatosis.

Labile plasma iron (LPI) represents the redox active component of non-transferrin-bound iron (NTBI). Its presence in thalassemic patients has been recently reported. The aim of the present study was to quantify LPI in HFE genetic hemochromatosis (GH) and to characterize the mechanisms accounting for its appearance. We studied 159 subjects subdivided into the following groups: (1) 23 with iron overloaded GH; (2) 14 with iron-depleted GH; (3) 26 with dysmetabolic hepatosiderosis; (4) 33 with alcoholic cirrhosis; (5) 63 healthy controls. Both NTBI and LPI were substantially higher in patients with iron-overloaded GH than in those with iron-depleted GH or in healthy controls. LPI was significantly correlated with serum transaminase increase in this group. LPI was elevated in the alcoholic cirrhosis subgroup of severely affected patients. LPI was found essentially when transferrin saturation exceeded 75%, regardless of the etiologic condition. Transferrin saturation above 75% was related to iron overload in GH and to liver failure in alcoholic cirrhosis. LPI is present in C282Y/C282Y hemochromatosis and may be a marker of toxicity due to its potential for catalyzing the generation of reactive oxygen radicals in vivo.

Adult↗
PubMed2005

[Human hepatic iron overload syndromes].

Recent advances in molecular genetics have led to a better understanding of hereditary iron overload syndromes, of which the most frequent are recessive HFE-hemochromatosis and, to a much lesser extent, dominant ferroportin disease. Acquired iron overload syndromes can be related to metabolic syndrome (insulin resistance syndrome), end-stage cirrhosis, or hematological disorders such as thalassemia and refractory anaemia.

Humans↗
PubMed2004

[Hemochromatosis].

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed2004

Prediction of liver fibrosis in patients with features of the metabolic syndrome regardless of alcohol consumption.

The aim of this study was to determine noninvasive predictive factors of significant liver fibrosis in patients with increased serum aminotransferases associated with features of metabolic syndrome (abdominal obesity, systemic hypertension, fasting hyperglycemia, and dyslipidemia). One hundred seventy-three patients were prospectively examined, regardless of alcohol consumption. Biometric, metabolic, and hepatic biochemical variables were tested for association with fibrosis assessed on liver biopsy according to the Metavir score system. Significant fibrosis, defined as Metavir scores F2, F3, or F4, was observed in 42 of 173 patients (24%). A logistic regression model and receiver operating characteristic curve were used to construct a simple index predictive of significant fibrosis. None of the patients with serum hyaluronate levels of 35 microg/L or less had significant fibrosis. In patients with serum hyaluronate levels >35 microg/L, no case of fibrosis stage F3 or F4 was found when serum carbohydrate-deficient transferrin/transferrin ratio was less than 0.9. In conclusion, in patients with increased serum aminotransferases associated with features of metabolic syndrome, a simple algorithm, including serum hyaluronate and serum carbohydrate-deficient transferrin/transferrin ratio, allows the exclusion of clinically relevant hepatic fibrosis, regardless of current or past alcohol consumption.

Alcohol Drinking↗
PubMed2004

[Should we support large-scale screening for genetic haemochromatosis in France?].

Genetic hemochromatosis meets the principal World Health Organization criteria for diseases warranting systematic population screening. Indeed, it is a frequent, late-onset, severe disease that is easy to diagnose and cure. However, its penetrance is much lower than thought prior to the discovery of the HFE1 gene, whose C282 Y mutation is responsible for more than 95% of cases with phenotypic expression. Moreover, several questions remain to be answered, notably concerning practical modalities [genotypic or phenotypic screening? at what age?, etc.], the risk of genetic discrimination, and cost-effectiveness. Current recommendations should include [i] broad information of the general population and GPs on early symptoms, [ii] transferrin saturation assay in all patients with symptoms compatible with hemochromatosis and, when elevated, genetic testing, the cost of which should be covered by public health insurance, [iii] both phenotypic and genotypic screening of all proband families, and [iv] implementation of regional and national pilot studies aimed at assessing disease penetrance and the acceptability and cost-effectiveness of large-scale screening.

France↗
PubMed2003

Iron and liver cancer.

Mechanisms whereby iron may act in carcinogenesis are induction of oxidative stress, facilitation of tumor growth, and modification of the immune system. Results of clinical and epidemiologic studies demonstrate a strong association between iron excess (even at mild levels) and the development of cancer at any site, but they do not indicate whether this reflects a causal link or an indirect association through other factors (i.e., aging, alcohol consumption, and insulin resistance). Findings obtained from experimental work are not conclusive with respect to a direct carcinogenic role of iron, but they support a carcinogenic or co-carcinogenic role of iron in chemically induced carcinogenesis.

Hemochromatosis↗
PubMed2003

High rate of long-term virological response after a 1-year course of interferon +/- ribavirin in chronic hepatitis C relapsers. Results of a 191 patients randomized trial.

UNLABELLED: We investigated the long-term efficacy of a 12-month course of interferon (IFN)+ribavirin in chronic hepatitis C relapsers. We randomized 191 relapsers with a 2:1 ratio to receive 3 million units three times a week of interferon alpha (IFN alpha)-2b+ribavirin (1-1.2 g/day) (group A=127 patients) or IFN alpha-2b (group B=60 patients) of same dosage and duration for 1 year. General and hepatitis C data of group A and B patients were similar. The main goal of the study was to determine the rate of sustained virological response evaluated 1 year after treatment. RESULTS: Virological sustained response (SR) was 61% and 12% for groups A and B, respectively (P<0.001). A significant histological improvement was observed in both treatment groups. The Metavir activity score became significantly lower in the IFN+ribavirin group than in the IFN group (P<0/0001). The Metavir fibrosis scores remained unchanged. Also, at the end of the treatment, the virological response was 69% (88/127) for group A and 33% (20/60) for group B (P<0.001). CONCLUSION: One-year retreatment of relapsers with the combination of IFN+ribavirin led to 61% of virological SR and to a significant improvement of histological activity. Therefore, the therapeutic schedule presented here can be considered of particular interest for the retreatment of relapsers.

Administration, Oral↗
PubMed2003

Circadian variations of transferrin saturation levels in iron-overloaded patients: implications for the screening of C282Y-linked haemochromatosis.

The phenotypic screening for genetic haemochromatosis (GH) relies upon the determination of transferrin saturation (TS). In large-scale screening programs, the time of blood sampling can be uneasy to control. We studied the circadian variations of TS at 08.00 hours, 12.00 hours, 18.00 hours and 00.00 hours in 46 C282Y homozygous patients (GH) and 47 non-GH patients (NH), to determine whether the time of blood sampling influenced the results of screening. In both groups, there were significant circadian variations in TS, with the highest values at 08.00 hours and the lowest at 00.00 hours. For any given time-point, TS was significantly higher in the GH group when compared with the NH group (P < 0.0001). For both groups, there was a significant decrease in TS between 08.00 hours and 00.00 hours (P < 0.0001) but this decrease was not as significant in GH when compared with NH patients (interaction P < 0.0073). Receiver operating characteristics (ROC) curves generated for TS at 08.00 hours, 12.00 hours, 18.00 hours and 00.00 hours, presented the same efficiency of diagnosis of GH, with TS threshold varying between 64% at 08.00 hours and 36% at 00.00 hours. In conclusion, for screening studies of C282Y homozygosity, determination of transferrin saturation may be performed at any time during the day.

Adult↗
PubMed2002

HFE based re-evaluation of heterozygous hemochromatosis.

Homozygosity for the C282Y mutation in the HFE gene is strongly associated with hereditary hemochromatosis. More than one subject out of 10 in the general population is a heterozygote for the C282Y mutation. In this study, we address whether or not conclusions drawn from HLA-based family studies regarding the expression of heterozygous hemochromatosis are applicable to C282Y heterozygotes. The correlation between HLA-inferred and HFE genotypes and the variation of serum iron tests according to HFE genotype and other factors were studied in persons from well-characterized hemochromatosis pedigrees. Subjects were tested for both C282Y and H63D mutations. The following factors were studied: age, sex, alcohol consumption, body mass index, liver function tests, serum lipids and glucose, serum iron, transferrin saturation, and ferritin. HLA-inferred heterozygotes were C282Y heterozygotes in only 70% and compound heterozygotes (i.e., heterozygotes for both C282Y and H63D) in 20%. C282Y heterozygotes did not differ from wild type homozygotes in terms of serum iron tests. Only compound heterozygotes presented with slightly increased transferrin saturation. On the other hand, increased serum ferritin was strongly associated with overweight or lipidic or glucose abnormalities. C282Y heterozygotes selected from family studies do not have greater serum iron tests than wild type homozygotes, except for compound heterozygotes, and therefore should not require special followup. The discovery of abnormal iron tests in a C282Y heterozygote should lead to workup for other causes of iron overload.

Amino Acid Substitution↗
PubMed2002

Indication of liver transplantation in severe alcoholic liver cirrhosis: quantitative evaluation and optimal timing.

BACKGROUND/AIMS: The aim of our study was to evaluate the proportion of patients with severe alcoholic cirrhosis who would need orthotopic liver transplantation (OLT) and to determine the optimal delay to evaluate an abstinent patient for transplantation. METHODS: Survival without OLT, improvement in liver function and need for OLT were studied in all patients admitted in 1997 for a first episode of Child-Pugh C alcoholic cirrhosis. RESULTS: Twenty-six percent (19/74) of patients died during the initial hospitalization. The cumulative survival rates after 6 months and 1, 2 and 3 years were 56, 36, 35 and 24%, respectively. One liver transplantation (1.3%, 95% confidence interval 0.0-3.9) was performed for persisting liver failure despite abstinence. Improvement of the Child-Pugh score was observed within 3 months in 66% of the abstinent patients. OLT was indicated in four patients without liver improvement despite abstinence, but was contraindicated in three. CONCLUSIONS: Only a few patients with severe alcoholic cirrhosis undergo OLT, since most of them do not stop drinking and/or die soon, and those becoming abstinent often improve their liver function. OLT should be considered when improvement in liver function is lacking after 3 months of abstinence.

Adult↗