C Jacquelinet

Unité Inserm U1077, Caen, Lower Normandy, France

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Publications (16)89.94 Total impact

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    ABSTRACT: Because 70% to 75% of patients with chronic hepatitis C either do not respond to or relapse after interferon (IFN) therapy, and because ursodeoxycholic acid (UDCA) has been shown to reduce aminotransferase levels in patients with chronic hepatitis, we undertook a prospective controlled randomized trial of IFN (group I) versus IFN plus UDCA (group II) in 80 patients with chronic hepatitis C. IFN was administered in both groups for 6 months (3 to 5 million units [MU] three times a week), and in group II UDCA (10 mg/kg/d) was administered with IFN and then alone for 3 additional months. Response to therapy was defined as the normalization of alanine transaminase (ALT) levels. The results showed that 6 months after cessation of IFN, 59% of responders had relapsed in group I but only 27% had relapsed in group II (P = .03). There was no difference between the two groups for the initial (month 6) and the late (months 15 and 18) response rates to IFN. There was no virological effect or significant histological improvement attributable to the addition of UDCA to IFN treatment. In conclusion, the results of this study show that the addition of UDCA to IFN therapy significantly prolongs the period for which serum ALT remain, within the normal range after discontinuation of IFN. Further studies would be required to determine whether UDCA has any potential for long-term amelioration of the histological severity of liver disease caused by hepatitis C virus (HCV) infection, and therefore, whether it could be advocated as an adjunct to antiviral therapy. (HEPATOLOGY 1995;21:322–327.)
    Hepatology 12/2005; 21(2):322 - 327. · 12.00 Impact Factor
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    ABSTRACT: 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.
    Liver international: official journal of the International Association for the Study of the Liver 08/2003; 23(4):255-61. · 3.87 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2001; 34:167-167.
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    ABSTRACT: To evaluate in a prospective study the prognostic factors of recurrent bleeding and mortality in patients presenting with high risk peptic ulcer bleeding routinely treated by endoscopic hemostasis. A multicenter study was carried out in 8 Western French hospitals in 144 patients with gastrointestinal bleeding peptic from ulcer type I or IIa, b as defined by Forrest classification. Thirty four and 38 parameters were studied respectively in order to predict recurrent bleeding and death. Significant predictive factors (P < 0.1) in univariate analysis were entered in a multivariate logistic regression analysis. Endoscopic hemostasis was performed in 108 of 144 cases (75%). Recurrent bleeding and death occurred in 39 (28%) and 22 cases (15%), respectively. By multivariate analysis, the only predictor of rebleeding was hypovolemia at admission. Predictors of death were ASA score, cardiovascular Goldman score and recurrent bleeding. In this study, prevalence of Helicobacter pylori infection was low (41%) but was not a predictive factor. In a selected population of peptic ulcer bleeding patients with high risk of rebleeding, prevalence of recurrent bleeding and death remains rather high, despite routine endoscopic hemostasis. In the era of endoscopic hemostasis, clinical parameters remain the best prognostic factors of peptic ulcer bleeding outcome.
    Gastroentérologie Clinique et Biologique 02/2000; 24(2):193-200. · 1.14 Impact Factor
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    ABSTRACT: The diagnosis of hemochromatosis is now possible for C282Y homozygous patients using noninvasive molecular genetic tests. The aim of this study was to define noninvasive factors predictive of severe fibrosis (bridging fibrosis or cirrhosis) to avoid unnecessary liver biopsies in such patients. Clinical and biological data were recorded at the time of diagnosis in 197 French C282Y homozygous patients, 52 (26%) of whom had severe fibrosis. Variables significantly linked to severe fibrosis using univariate analysis were entered into a multivariate stepwise analysis. These variables were combined to obtain a simple index allowing for prediction of severe fibrosis. Serum ferritin, hepatomegaly, and serum aspartate aminotransferase were selected using multivariate analysis. Their combination applied to the 96 patients with ferritin level of </=1000 microgram/L, normal aspartate aminotransferase values, and absence of hepatomegaly showed that no severe fibrosis was encountered in this subgroup of patients. The results were validated in 113 C282Y homozygous patients in Canada with a good reproducibility of negative prediction but a poor reproducibility of the positive prediction of severe fibrosis. In C282Y homozygous patients, the diagnosis of severe fibrosis relies on liver biopsy, but absence of severe fibrosis can be accurately predicted in most patients on the basis of simple clinical and biochemical variables.
    Gastroenterology 11/1998; 115(4):929-36. · 12.82 Impact Factor
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    ABSTRACT: We studied the activities of the new fluoroquinolones clinafloxacin, levofloxacin, ofloxacin, and sparfloxacin alone or in combination on the intracellular growth of Listeria monocytogenes. Against intracellular growth of the four strains tested, a similar reduction of the bacterial count was obtained with clinafloxacin at the dose of 10 x MIC (delta log10 CFU/ml = -2.19 +/- 0.24), with levofloxacin at 8 x MIC (delta log10 CFU/ml = -2.28 +/- 0.25), and with sparfloxacin at 4 x MIC (delta log10 CFU/ml = -2.16 +/- 0.21) after 24 h of incubation. The combination of the quinolones with trimethoprim-sulfamethoxazole or amoxicillin did not show a substantial increase in activity compared to the fluoroquinolone alone. Antagonism with rifampin was strongly suggested. No modification of the MIC was observed after 20 successive infections of HeLa cells and contact with subinhibitory concentrations of clinafloxacin, levofloxacin, and sparfloxacin for 24 h. We conclude that clinafloxacin, levofloxacin, or sparfloxacin could represent a therapeutic alternative to amoxicillin for the treatment of Listeria infections in adults, especially clinafloxacin, whose MIC is low (0.06 to 0.12 micrograms/ml), and whose best activity against intracellular L. monocytogenes was obtained at a concentration of 1.2 micrograms/ml, which is similar to clinically achievable levels. The results must be confirmed in an experimental model.
    Antimicrobial Agents and Chemotherapy 02/1997; 41(1):60-5. · 4.57 Impact Factor
  • Annales Francaises D Anesthesie Et De Reanimation - ANN FR ANESTH REANIM. 01/1996; 15(6):809-809.
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    ABSTRACT: To compare the advantages of endoscopic ligation and endoscopic sclerotherapy for bleeding esophageal varices, published randomized clinical trials were critically reviewed by meta-analysis. Only ten clinical trials concerning a history of recent or active bleeding esophageal varices were included. The methodology, population, treatment and outcomes of each relevant trial were evaluated by duplicate independent review. Endoscopic sclerotherapy compared to banding ligation significantly increased the rate of rebleeding (OR: 1.6; 95% IC: 1.1-2.3) without increasing early mortality compared to endoscopic banding ligation (OR: 1.3; 95% IC: 0.8-1.9). The rate of varice eradication associated with these two types of treatment was not different (OR: 0.9; 95% IC: 0.6-1.3) but was obtained more quickly with endoscopic banding ligation (3.8 +/- 1.6 versus 5.8 +/- 2.2; P < 0.05). The rate of complications was higher after sclerotherapy (OR: 2.5; 95% IC: 1.7-3.7), in those cases with a positive heterogeneity test. This meta-analysis shows a lower morbidity with endoscopic banding ligation in patients with variceal hemorrhage. The most important advantage of endoscopic banding ligation was the reduction of the rate of rebleeding.
    Gastroentérologie Clinique et Biologique 11/1995; 19(11):914-20. · 1.14 Impact Factor
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    ABSTRACT: To determine the prognostic value of plasma viremia in long-term zidovudine (AZT)-treated HIV-infected patients, HIV-1 plasma viremia (PV) was quantified in 28 HIV-infected patients before and during AZT long-term treatment; the follow-up also included p24 antigenemia and CD4 cell counts. The variations of these markers during the follow-up period, the correlation with the clinical outcome (progressors versus nonprogressors), and the discrepancies between PV and surrogate markers were then analyzed. A significant and stable decrease in PV titer was observed in only nonprogressors (Friedman test, p < 0.005). At the end of follow-up, 11 (73%) of the 15 non-progressors were PV responders (patients who remained or became PV- long-term), whereas all the 13 progressors were PV nonresponders (patients who remained or became PV+). These results indicated a strong correlation between PV and clinical outcome (Fischer's exact test, p < 0.0001). The persistence, increase, or reappearance of viral replication appeared to be an important predictor of poor clinical outcome in HIV-infected patients under AZT treatment. This finding could provide a rational basis to help the clinician's decision in the clinical treatment of HIV-infected patients.
    Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 08/1995; 9(3):243-8.
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    ABSTRACT: Because 70% to 75% of patients with chronic hepatitis C either do not respond to or relapse after interferon (IFN) therapy, and because ursodeoxycholic acid (UDCA) has been shown to reduce aminotransferase levels in patients with chronic hepatitis, we undertook a prospective controlled randomized trial of IFN (group I) versus IFN plus UDCA (group II) in 80 patients with chronic hepatitis C. IFN was administered in both groups for 6 months (3 to 5 million units [MU] three times a week), and in group II UDCA (10 mg/kg/d) was administered with IFN and then alone for 3 additional months. Response to therapy was defined as the normalization of alanine transaminase (ALT) levels. The results showed that 6 months after cessation of IFN, 59% of responders had relapsed in group I but only 27% had relapsed in group II (P = .03). There was no difference between the two groups for the initial (month 6) and the late (months 15 and 18) response rates to IFN. There was no virological effect or significant histological improvement attributable to the addition of UDCA to IFN treatment. In conclusion, the results of this study show that the addition of UDCA to IFN therapy significantly prolongs the period for which serum ALT remain, within the normal range after discontinuation of IFN. Further studies would be required to determine whether UDCA has any potential for long-term amelioration of the histological severity of liver disease caused by hepatitis C virus (HCV) infection, and, therefore, whether it could be advocated as an adjunct to antiviral therapy.
    Hepatology 03/1995; 21(2):322-7. · 12.00 Impact Factor
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    ABSTRACT: Computed tomography (CT) scanning is not highly sensitive in the assessment of liver iron content and magnetic resonance imaging (MRI) appears to be more efficient. The aim of this study was to determine the effectiveness of MRI in the evaluation of liver iron content using a standard spin-echo technique. The study included 23 patients with genetic hemochromatosis and 24 non-iron-overloaded patients as controls. A comparison was made of: (a) MRI signal intensity of liver, spleen, paravertebral muscles and subcutaneous adipose tissue using two different spin-echo sequences (SE 500/28; SE 2000/28,56); (b) liver attenuation determined by a single energy CT scan; and (c) a biochemical determination of hepatic iron. There was a significant decrease in liver signal intensity in the genetic hemochromatosis group (256 +/- 201, mean +/- S.D.) compared with the control group (801 +/- 413, p less than 0.001), but there was no correlation with liver iron concentration. However, such a correlation was found and was even more highly significant than in CT when the ratio between the liver and another organ was taken into account. For a lower limit of liver/spleen ratio calculated at 0.46 (mean 2 S.D. in the control group), the specificity (0.96) of MRI was satisfactory, but the sensitivity (0.78) remained insufficient (MRI being unable to detect an iron overload of up to 125 mumol/g). Hopefully, these results might be improved in the near future by using more sensitive sequences such as gradient echo sequences.
    Journal of Hepatology 08/1992; 15(3):304-8. · 9.86 Impact Factor
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    ABSTRACT: Liver pathology was assessed in 135 patients with well-defined genetic hemochromatosis ranging from mild disease to severe overload. Three lesions were clearly linked to iron-overload intensity--scarce sidero-necrosis, mild inflammation, and progressive fibrosis. Iron-free foci made of typical or dysplastic hepatocytes were found in 7.4% of the cases. An original grading allowed a reliable quantification of iron and the study of cellular and lobular distribution of iron, which permitted (a) the accurate identification of a decreasing iron gradient in hepatocytes from zone 1 to zone 3 in all cases, (b) the definition of a threshold hepatocytic/mesenchymal iron ratio related to the appearance of sidero-necrosis and to the development of fibrosis, and (c) demonstration that non-iron-related factors (mainly alcoholism) could shift iron from hepatocytes to sinusoidal cells without an increase in the total liver iron amount. This study provides a dynamic view of the iron overload process and suggests that sidero-necrosis and progressive sinusoidal iron overload play a role in the development of fibrosis in human genetic hemochromatosis.
    Gastroenterology 07/1992; 102(6):2050-9. · 12.82 Impact Factor
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    ABSTRACT: Serum hepatitis B virus (HBV) infection markers were studied in 272 patients with homozygous genetic haemochromatosis complicated (n = 33) or not (n = 239) with primary liver cancer (PLC). Controls consisted of 255 029 healthy blood donors from whom age- and sex-matched control groups were extracted for statistical evaluation using the Fisher exact test. In blood donors, HBsAg was positive in 0.075% of males and 0.04% of females. This population was not screened for anti-Hbs. Anti-Hbc alone (without HBsAg) was present in 3.7% of men and 1.8% of women. In patients with genetic haemochromatosis without liver cancer (183 males, 45.6 +/- 11.3 yrs and 56 women, 48 +/- 12.4 yrs), HBsAg was found in 1.1% of men and in none of the women. Anti-HBs was present in 7.3% of males and 1.8% of females. Anti-HBc alone was found in 13% of males (p less than 0.005 vs. controls) and 2.1% of females. From male patients with primary liver cancer complicating genetic haemochromatosis (32 males, 61.7 +/- 6.8 yrs and one female), 6.2% were HBsAg positive, 3.4% were anti-HBs positive and 16.6% anti-HBc positive (p = 0.05 vs. controls). No serum HBV marker was found in the woman. In conclusion, the prevalence of HBV infection markers--especially anti-HBc--is significantly increased in patients with genetic haemochromatosis complicated or not with primary liver cancer.
    Journal of Hepatology 12/1991; 13(3):286-90. · 9.86 Impact Factor
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    ABSTRACT: Twenty-nine patients with chronic hepatitis B, presenting both hepatitis B surface antigen and hepatitis B virus deoxyribonucleic acid in serum, were studied in a randomized trial treatment consisting of oral prednisolone for 28 days followed 14 days after steroid withdrawal, by either a 55 s.c. injection course of 5 M unit recombinant human alpha-interferon (group 1, 14 patients) or by adenine-arabinoside (for 21 days) combined from the fourteenth day on with the same 55 s.c. injection schedule of interferon (IFN) (group 2, 15 cases). The two groups were well matched with respect to demographic, biochemical, virological and histologic features. Significant side-effects leading to premature discontinuation of interferon were observed in only four cases in group 2 and were always reversible. Efficacy was judged on a mean follow-up period of 17 months. For the whole population, 17 patients (59%) exhibited a sustained serum hepatitis B virus deoxyribonucleic acid disappearance which corresponded to a marked improvement in liver function as demonstrated by a quasi-normalization of their serum transaminase values (ALT with n less than 22 UI/l: 23 +/- 24 vs. 139 +/- 115 before treatment; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
    Journal of Hepatology 04/1991; 12(2):181-9. · 9.86 Impact Factor
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    ABSTRACT: Twenty-nine patients with chronic hepatitis B, presenting both hepatitis B surface antigen and hepatitis B virus deoxyribonucleic acid in serum, were studied in a randomized trial treatment consisting of oral prednisolone for 28 days followed 14 days after steroid withdrawal, by either a 55 s.c. injection course of 5 M unit recombinant human α-interferon (group 1, 14 patients) or by adenine-arabinoside (for 21 days) combined from the forteenth day on with the same 55 s.c. injection schedule of interferon (IFN) (group 2, 15 cases). The two groups were well matched with respect to demographic, biochemical, virological and histologic features. Significant side-effects leading to premature discontinuation of interferon were observed in only four cases in group 2 and were always reversible. Efficacy was judged on a mean follow-up period of 17 months. For the whole population, 17 patients (59%) exhibited a sustained serum hepatitis B virus deoxyribonucleic acid disappearance which corresponded to a marked improvement in liver function as demonstrated by a quasi-normalization of their serum transaminase values (ALT with n < 22 UI/l: 23 ± 24 vs. 139 ± 115 before treatment; P < 0.001). Comparison of the two groups revealed a tendency towards better results in the triple therapy group in view of a higher transient or sustained HBV-DNA clearance ( vs. in group 1; p = 0.042; Fisher's exact test) and a higher HBe seroconversion rate ( vs. ; chi-square) reaching 60% (vs. 36% in group 1) when taking into account two patients (one in each group) with initially HBeAg(−) Anti-HBe(+) HBV-DNA (+) chronic active hepatitis who developed a sustained HBV-DNA loss with ALT normalization. These findings confirm the interest of associating corticosteroid pretreatment and antiviral therapy in chronic hepatitis B and suggest that this therapeutic approach could be improved by combining two antiviral agents.
    Journal of Hepatology - J HEPATOL. 01/1991; 12(2):181-189.
  • Journal of Hepatology - J HEPATOL. 01/1990; 11.