J Dumortier

Hospices Civils de Lyon, Lyons, Rhône-Alpes, France

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Publications (134)437.62 Total impact

  • A Lachaux, J Dumortier
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    ABSTRACT: Apha-1-antitrypsin deficiency is an autosomal recessive genetic disorder seen in all races. The molecular defect is a specific mutation of the SERPINA1 gene leading to synthesis of an abnormal protein (alpha-1-antitrypsin Z) that cannot be secreted and polymerizes in the endoplasmic reticulum of hepatocytes. The inter-individual variability in the responses to intracellular stress induced by the accumulation of abnormal polymers and the mechanisms allowing their degradation is, without doubt, responsible for the different clinical manifestations of the disease. The disease affects the liver where the abnormal protein is synthesized and the lung, which is its place of action. Liver involvement is well recognized in homozygous infants of the phenotype ZZ. In this situation the disease may present a varying picture from neonatal cholestasis (about 15% of neonatal defects) to cirrhosis. However, evolution towards cirrhosis affects less than 3% of infants with the ZZ phenotype and it is preceded in 80% of cases by neonatal cholestasis. In adolescents or adults the manifestations associated with alpha-1-antitrypsin deficiency are usually limited to biochemical abnormalities but may lead to cirrhosis or hepatocellular carcinoma. The hepatic disorder and its complications are treated symptomatically though the pulmonary involvement may benefit from substitution treatment. More specific treatments targeting the molecular and cellular abnormalities are the subject of research.
    Revue des Maladies Respiratoires 04/2014; 31(4):357-364. · 0.50 Impact Factor
  • A. Lachaux, J. Dumortier
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    ABSTRACT: Apha-1-antitrypsin deficiency is an autosomal recessive genetic disorder seen in all races. The molecular defect is a specific mutation of the SERPINA1 gene leading to synthesis of an abnormal protein (alpha-1-antitrypsin Z) that cannot be secreted and polymerizes in the endoplasmic reticulum of hepatocytes. The inter-individual variability in the responses to intracellular stress induced by the accumulation of abnormal polymers and the mechanisms allowing their degradation is, without doubt, responsible for the different clinical manifestations of the disease. The disease affects the liver where the abnormal protein is synthesized and the lung, which is its place of action. Liver involvement is well recognized in homozygous infants of the phenotype ZZ. In this situation the disease may present a varying picture from neonatal cholestasis (about 15% of neonatal defects) to cirrhosis. However, evolution towards cirrhosis affects less than 3% of infants with the ZZ phenotype and it is preceded in 80% of cases by neonatal cholestasis. In adolescents or adults the manifestations associated with alpha-1-antitrypsin deficiency are usually limited to biochemical abnormalities but may lead to cirrhosis or hepatocellular carcinoma. The hepatic disorder and its complications are treated symptomatically though the pulmonary involvement may benefit from substitution treatment. More specific treatments targeting the molecular and cellular abnormalities are the subject of research.
    Revue des Maladies Respiratoires. 01/2014;
  • Gastroentérologie Clinique et Biologique 12/2013; · 0.80 Impact Factor
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    ABSTRACT: Renal dysfunction is frequent in liver cirrhosis and is a strong prognostic predictor of orthotropic liver transplantation (OLT) outcome. Therefore, an accurate evaluation of the glomerular filtration rate (GFR) is crucial in pre-OLT patients. However, in these patients, plasma creatinine (Pcr) is inaccurate and the place of serum cystatine C (CystC) is still debated. New GFR-predicting equations, based on standardized assays of Pcr and/or CystC, have been recently recommended in the general population but their performance in cirrhotic patients has been rarely studied. We evaluated the performance of the recently published Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI-Pcr, CKD-EPI-CystC, and CKD-EPI-Pcr-CystC) and the more classical ones (4- and 6-variable MDRD and Hoek formulas) in cirrhotic patients referred for renal evaluation before OLT. Inulin clearance was performed in 202 consecutive patients together with the determination of Pcr and CystC with assays traceable to primary reference materials. The performance of the GFR-predicting equations was evaluated according to ascites severity (no, moderate, or refractory) and to hepatic and renal dysfunctions (MELD score ≤ or > 15 and KDOQI stages, respectively). In the whole population, CystC-based equations showed a better performance than Pcr-based ones (lower bias and higher 10% and 30% accuracies). CKD-EPI-CystC equation showed the best performance whatever the ascites severity and in presence of a significant renal dysfunction (GFR< 60 mL/min/1.73 m(2) ). Conclusions: Pcr-based GFR predicting equations are not reliable in pre-OLT patients even when an IDMS-traceable enzymatic Pcr assay is used. Whenever a CystC-assay traceable to primary reference materials is performed and when true a measurement of GFR is not possible, CystC-based equations, especially CKD-EPI-CystC, may be recommended to evaluate renal function and for KDOQI staging. (Hepatology 2013;).
    Hepatology 10/2013; · 12.00 Impact Factor
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    ABSTRACT: During 1982-2007, alveolar echinococcosis (AE) was diagnosed in 407 patients in France, a country previously known to register half of all European patients. To better define high-risk groups in France, we conducted a national registry-based study to identify areas where persons were at risk and spatial clusters of cases. We interviewed 180 AE patients about their way of life and compared responses to those of 517 controls. We found that almost all AE patients lived in 22 départements in eastern and central France (relative risk 78.63, 95% CI 52.84-117.02). Classification and regression tree analysis showed that the main risk factor was living in AE-endemic areas. There, most at-risk populations lived in rural settings (odds ratio [OR] 66.67, 95% CI 6.21-464.51 for farmers and OR 6.98, 95% CI 2.88-18.25 for other persons) or gardened in nonrural settings (OR 4.30, 95% CI 1.82-10.91). These findings can help sensitization campaigns focus on specific groups.
    Emerging Infectious Diseases 05/2013; 19(5):721-8. · 6.79 Impact Factor
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    ABSTRACT: The aim of this study was to generate an improved prognostic model for predicting recurrence in liver transplant candidates with hepatocellular carcinoma (HCC). Predictors of recurrence were tested by a Cox model analysis in a training cohort of 537 patients transplanted for HCC. A prognostic score was developed and validated in a national cohort of 435 patients followed up prospectively. α-Fetoprotein (AFP) independently predicted tumor recurrence and correlated with vascular invasion and differentiation. At a Cox score threshold of 0.7 (area under the receiver operating characteristic curve, 0.701; 95% confidence interval, 0.63-0.76; accuracy, 75.8%), a model combining log(10) AFP, tumor size, and number was highly predictive of tumor recurrence and death. By using a simplified version of the model, with untransformed AFP values, a cut-off value of 2 was identified. In the validation cohort, a score greater than 2 predicted a marked increase in 5-year risk of recurrence (50.6% ± 10.2% vs 8.8% ± 1.7%; P < .001) and decreased survival (47.5% ± 8.1% vs 67.8% ± 3.4%; P = .002) as compared with others. Among patients exceeding Milan criteria, a score of 2 or lower identified a subgroup of patients with AFP levels less than 100 ng/mL with a low 5-year risk of recurrence (14.4% ± 5.3% vs 47.6% ± 11.1%; P = .006). Among patients within Milan criteria, a score greater than 2 identified a subgroup of patients with AFP levels greater than 1000 ng/mL at high risk of recurrence (37.1% ± 8.9% vs 13.3% ± 2.0%; P < .001). Net reclassification improvement showed that predictability of the AFP model was superior to Milan criteria. Prediction of tumor recurrence is improved significantly by a model that incorporates AFP. We propose the adoption of new selection criteria for HCC transplant candidates, taking into account AFP.
    Gastroenterology 06/2012; 143(4):986-994.e3. · 12.82 Impact Factor
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    ABSTRACT: A 6-month abstinence from alcohol is usually required before patients with severe alcoholic hepatitis are considered for liver transplantation. Patients whose hepatitis is not responding to medical therapy have a 6-month survival rate of approximately 30%. Since most alcoholic hepatitis deaths occur within 2 months, early liver transplantation is attractive but controversial. We selected patients from seven centers for early liver transplantation. The patients had no prior episodes of alcoholic hepatitis and had scores of 0.45 or higher according to the Lille model (which calculates scores ranging from 0 to 1, with a score ≥ 0.45 indicating nonresponse to medical therapy and an increased risk of death in the absence of transplantation) or rapid worsening of liver function despite medical therapy. Selected patients also had supportive family members, no severe coexisting conditions, and a commitment to alcohol abstinence. Survival was compared between patients who underwent early liver transplantation and matched patients who did not. In all, 26 patients with severe alcoholic hepatitis at high risk of death (median Lille score, 0.88) were selected and placed on the list for a liver transplant within a median of 13 days after nonresponse to medical therapy. Fewer than 2% of patients admitted for an episode of severe alcoholic hepatitis were selected. The centers used 2.9% of available grafts for this indication. The cumulative 6-month survival rate (±SE) was higher among patients who received early transplantation than among those who did not (77 ± 8% vs. 23 ± 8%, P<0.001). This benefit of early transplantation was maintained through 2 years of follow-up (hazard ratio, 6.08; P = 0.004). Three patients resumed drinking alcohol: one at 720 days, one at 740 days, and one at 1140 days after transplantation. Early liver transplantation can improve survival in patients with a first episode of severe alcoholic hepatitis not responding to medical therapy. (Funded by Société Nationale Française de Gastroentérologie.).
    New England Journal of Medicine 11/2011; 365(19):1790-800. · 54.42 Impact Factor
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    ABSTRACT: The combination of tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) is used extensively to treat HIV infection and also has potent activity against hepatitis B virus (HBV) infection. The aim of this study was to assess the efficacy and tolerance of TDF + FTC in patients with chronic hepatitis B (CHB). Seventy eight consecutive CHB patients from five European centers were included. All started a TDF + FTC combination between October 2005 and March 2010. Virological, biochemical, and clinical data were recorded during follow-up. Tolerance was also monitored. Patients were classified into either treatment simplification (TS), where efficacy of the previous treatment was obtained at TDF + FTC initiation, and treatment intensification (TI), where the previous line of therapy had failed. TDF + FTC was given as a TI to 54 patients (69%) and as a TS to 24 (31%). Among patients with TI, 83% were males. The median baseline HBV-DNA was 4.4 log10 IU/mL, and median alanine-transaminase (ALT) was 1.10 × ULN. Sixty percent were HBeAg positive, 47% had significant fibrosis (≥ F3 Metavir equivalent), and 29% had confirmed cirrhosis. Median treatment duration was 76 weeks (interquartile range 60-116). Kaplan-Meier analysis showed that, 48 weeks after TI, the probability of being HBV-DNA becoming undetectable was 76%, and reached 94% at week 96. No viral breakthrough occurred. Patients with TS (87% males, median baseline HBV-DNA 1.1 log10 IU/mL, median ALT 0.79 × ULN, 33% HBeAg positive, 61% with significant fibrosis) were treated for a median duration of 76 weeks. In this subgroup, all patients but one remained HBV-DNA undetectable and no ALT flare-up occurred during follow-up. Creatinine levels did not show kidney-function deterioration in either group of patients. After a median follow-up of > 76 weeks, the TDF + FTC combination showed encouraging antiviral efficacy and a good safety profile in all patients with CHB. TDF + FTC may represent an interesting clinical option to simplify therapy and increase the barrier to resistance, which should be assessed in the long term.
    Antiviral research 07/2011; 92(1):90-5. · 3.61 Impact Factor
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    ABSTRACT: New-onset diabetes mellitus (NODM) has important implications for long-term outcome following liver transplantation. To evaluate the impact of conversion from tacrolimus to cyclosporine in liver transplant patients presenting NODM. In a 12-month pilot study, 39 liver transplant patients with NODM were converted from tacrolimus to cyclosporine. Most patients (59%) were receiving antidiabetic therapy (18% insulin, 41% oral) and all patients had received dietary advice prior to the study. At month 12, NODM had significantly resolved (FBG<7 mmol/L without treatment) in 36% of patients (95% CI 20.8-51.0%). In the 16 patients not receiving antidiabetic drugs at baseline, mean FBG decreased from 8.1 mmol/L to 6.6 mmol/L (P=0.008) and mean HbA(1c) decreased from 6.4 to 6.0% (P=0.05). Steroids were stopped rapidly in the nine patients receiving steroids at inclusion but NODM resolution was observed in only one of these nine patients. No significant factors were identified that could have affected NODM resolution. There were three episodes of biopsy-proven acute rejection (7.7%), no graft losses and one death. Overall, cyclosporine tolerance was good with no significant change in creatinine clearance at month 12. Total cholesterol increased from 4.6 mmol/L to 5.1 mmol/L (P<0.001). These results suggest that liver transplant patients with NODM may benefit from conversion to cyclosporine from tacrolimus through improved glucose metabolism. Confirmation in a prospective, randomized comparative study is required.
    Gastroentérologie Clinique et Biologique 06/2011; 35(6-7):482-8. · 0.80 Impact Factor
  • Nephrologie & Therapeutique - NEPHROL THER. 01/2011; 7(5):375-375.
  • Nephrologie & Therapeutique - NEPHROL THER. 01/2011; 7(5):370-371.
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    ABSTRACT: Transcatheter local thrombolytic therapy in patients with portosplanchnic venous thrombosis has been used in few cases. Here, we present our single-center experience with transcatheter thrombolytic therapy in three patients with extensive refractory portal and transjugular intrahepatic portosystemic shunt (TIPS) thrombosis. Thrombolytic therapy was successful for all three patients. Two patients developed minor procedure-related bleeding. Local thrombolysis could be proposed in case of TIPS thrombosis for patients in whom the venous flow cannot be restored by using conventional anticoagulant therapy and stent mechanical revision.
    Gastroentérologie Clinique et Biologique 10/2010; 34(12):721-5. · 1.14 Impact Factor
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    ABSTRACT: Mycophenolate mofetil (MMF) is a cornerstone immunosuppressive drug after liver transplantation (OLT). The aim of this study was to evaluate the long term results of the addition of MMF in maintenance OLT recipients. From 1996 to 2006, MMF was introduced because of (1) histologic features of rejection or (2) calcineurin inhibitor (CNI) toxicity in order to reduce CNI dosage. The study population included 208 patients (median, age 54 ± 9 years), with a median delay between OLT and MMF introduction of 54 ± 43 months. The median dosage of MMF was 1180 mg/d at the end of follow-up. After a median follow-up of 50 ± 26 months, 26.4% of the patients taking MMF did present ≥1 side effect and MMF discontinuation rate was 13.8% (transient in 3.8%). The main side effects were digestive disorders (45%), pruritus ± rash ± mucitis (12.7%), and myelosuppression (16.4%). MMF was withdrawn because of digestive disorders (17.2%), pruritus ± rash ± mucitis (17.2%), and myelosuppression (24.1%). The mean glomerular filtration rate as calculated by the Cockcroft-Gault formula value significantly increased after the introduction of MMF (58.1 vs 71.4 mL/min; paired t-test; P < .01). Improvement of renal function was significantly associated with initial association with tacrolimus (vs cyclosporine), initial trough level of cyclosporine (not tacrolimus), delay between OLT and MMF introduction, and age of renal impairment. Our results suggest that the introduction of MMF in OLT maintenance recipients is efficient and well-tolerated (one quarter of the patients presented significant side effects, leading to treatment discontinuation in 10% of the patients).
    Transplantation Proceedings 09/2010; 42(7):2602-6. · 0.95 Impact Factor
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    ABSTRACT: Tuberous sclerosis complex is a genetic multisystem disorder characterised by widespread hamartomas in several organs, including the brain, heart, skin, eyes, kidney, lung, and liver. Hepatic multiple, bilateral angiomyolipomas are a rare and usually asymptomatic complication in patients with tuberous sclerosis. We report here the case of a patient who needed liver transplantation because of debilitating manifestations and mechanical complications of massive liver involvement by multiple angiomyolipomas (severe malnutrition, anorexia and abdominal pain). Seventeen tumors, from 2 to 16 cm in diameter, were identified at examination of the liver explant. No feature suggestive of malignant behaviour was identified at histological examination. In conclusion, this unusual indication of liver transplantation underlines the interest of this therapeutic approach for benign tumors for which the multiplicity of the lesions and their huge volume prevent any attempt at surgical resection.
    Gastroentérologie Clinique et Biologique 09/2010; 34(8-9):494-8. · 1.14 Impact Factor
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    ABSTRACT: Accurate evaluation of the glomerular filtration rate (GFR) in patients awaiting liver transplantation is important because they have a greater risk of impaired renal function. A major percentage of these patients have alcoholic cirrhosis, and the accuracy of bedside used GFR estimates have not been specifically evaluated in this group. The aim of this study was to evaluate the validity of the simplified Modification of Diet in Renal Diseases (MDRD) and Cockcroft and Gault (CG) formulas in patients with decompensated alcoholic cirrhosis in comparison to inulin clearance as the reference method. GFR estimated by the simplified MDRD and CG formulas were retrospectively compared to the true GFR measured by inulin clearance in a single-centre cohort of 148 patients with decompensated alcoholic cirrhosis. Mean ± standard deviation of age, body mass index, inulin clearance and MDRD and CG estimates were 54.4 ± 6.9 years, 26.5 ± 4.7 kg/m(2), 76.9 ± 28.0 mL/min per 1.73 m(2), 99.4 ± 34.0 mL/min per 1.73 m(2) and 98.7 ± 32.0 mL/min per 1.73 m(2), respectively; 70% of the patients had a GFR, measured by inulin clearance, below 90 mL/min per 1.73 m(2). The difference between estimated GFR and true GFR were 23 ± 23 mL/min per 1.73 m(2) for MDRD and 22 ± 20 mL/min per 1.73 m(2) for Cockcroft and Gault. The simplified MDRD and CG formulas largely overestimated GFR in patients with decompensated alcoholic cirrhosis. Results of such bedside formulas should be interpreted with caution in these patients.
    Nephrology Dialysis Transplantation 05/2010; 25(11):3569-75. · 3.37 Impact Factor
  • Journal of clinical gastroenterology 03/2010; 44(8):593-4. · 2.21 Impact Factor
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    ABSTRACT: When hepatic artery reconstruction is required during hepatic transplantation, this is generally performed with donor vessels. We describe two cases requiring a prosthesis. The first case was a 58-year-old man transplanted for cirrhosis complicated by hepatocellular carcinoma. During transplantation, dissection of the celiac trunk occurred due to arterial embolization and the use of the patient's vessels was impossible. An extra-anatomical bypass between the infra-renal aorta and the donor hepatic artery was performed via the interposition of a graft tube. The second case was a 52-year-old man transplanted for cirrhosis complicated by hepatocellular carcinoma. On day 16, a ruptured anastomosis was suspected and the patient underwent emergency revision laparotomy. Arterial revascularisation was performed with an aortohepatic bypass using a synthetic GoreTex((R)) graft. Patient follow-up was uneventful.
    Gastroentérologie Clinique et Biologique 02/2010; 34(2):111-4. · 1.14 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2010; 52.
  • Journal of Hepatology - J HEPATOL. 01/2010; 52.
  • Journal of Hepatology - J HEPATOL. 01/2010; 52.

Publication Stats

697 Citations
437.62 Total Impact Points

Institutions

  • 2006–2014
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
  • 1998–2009
    • CHU de Lyon - Groupement Hospitalier Edouard Herriot
      Lyons, Rhône-Alpes, France
  • 2003–2006
    • CHU de Lyon - Hôpital Gériatrique des Charpennes
      Lyons, Rhône-Alpes, France
  • 1999–2000
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
    • Unité Inserm U1077
      Caen, Lower Normandy, France