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Biomedical subjects

Didier Samuel

Publications and source records attributed to Didier Samuel.

At least 19 recordsLinked to original sources
PubMed2006

Solitary pulmonary metastasis arising thirteen years after liver transplantation for HBV-related hepatocellular carcinoma.

We described a 59-year-old male patient who underwent liver transplantation in 1989 for hepatocellular carcinoma (HCC) complicating hepatitis B virus (HBV) cirrhosis. In 2001 (12 years after liver transplantation), he developed a lung metastasis of HCC without intrahepatic recurrence and the resection was done. In July 2003, he was symptom free without any recurrence. HCC metastasis can develop even after a very long time of liver transplantation. Many HCCs grow slowly, and the growth rate of recurrent tumors in patients receiving immunosuppressive therapy is significantly greater than that of those who do not receive immunosuppressive therapy.

Carcinoma, Hepatocellular↗
PubMed2006

Characteristics of patients with chronic hepatitis B in France: predominant frequency of HBe antigen negative cases.

BACKGROUND/AIMS: An increasing prevalence of HBe antigen (HBeAg) negative chronic hepatitis B has been recently reported in many countries. The aim of this study was to analyze the frequency and the characteristics of HBeAg-negative as compared with HBeAg-positive chronic hepatitis B in France. METHODS: Eight hundred and sixty-five patients with histologically proven chronic hepatitis B seen in 26 University centers were included. The proportion with HBeAg-negative chronic hepatitis B was 72% and higher in patients born in Africa, Middle East, Eastern, and Southern Europe than in those of French or Asian origin. HBeAg-negative patients were significantly older (p<0.001) and had lower ALT levels and HBV DNA serum levels (p<0.01) than HBeAg-positive patients. An unknown source of infection was more prevalent in HBeAg-negative patients (p<0.05). Fibrosis score (p<0.05) and proportion of cirrhosis (p<0.01) were significantly higher in HBeAg-negative patients. Age older than 50 years, male gender and viral load lower than 5 logs10 copies/mL were independently associated with cirrhosis. RESULTS: HBeAg-negative chronic hepatitis B is predominant in France. This observation is important for an optimized clinical management and future therapeutic trials in chronic hepatitis B.

Adult↗
PubMed2006

Liver retransplantation: a model for determining long-term survival.

BACKGROUND: Because of the worse results from retransplantation in relation to the initial liver transplantation, there is a need to refine the indication for retransplantation, such that fair distribution of this benefit is obtained. METHODS: This was a study of 139 patients who underwent liver retransplantation. Thirty variables were studied: 18 relating to the recipient and 12 to the donor. All the independent variables were initially compared with the length of survival using univariate analyses. Variables presenting significance were compared with the dependent variable of length of survival, to determine which factors were related to longer survival among patients, when evaluated together. RESULTS: A multivariate model for determining long-term survival among patients with retransplants was built up using the following variables: recipient's age, creatinine, urgency of retransplantation and early failure of the first graft. Through this multivariate model it was possible to determine a score that was categorized according to tertile distributions (below the 33rd percentile, score <24; 33rd to 66th percentile, 24 < or = score < or = 32; above the 66th percentile, score > 32). One-year, 3-year, and 5-year patient survival rates following retransplantation were respectively 85%, 82%, and 77% for scores <24; 69%, 66%, and 61% for scores between 24 and 32; and 21%, 19%, and 16% for scores >32 (P < 0.0001). CONCLUSION: The variables of recipient's age, creatinine, urgency of retransplantation, and early failure of the initial transplantation were factors that were independently related to the long-term survival of patients with liver retransplants.

Adolescent↗
PubMed2006

Safety, tolerability, and efficacy of everolimus in de novo liver transplant recipients: 12- and 36-month results.

Everolimus is a macrolide immunosuppressive agent with known consistent absorption. In this double-blind study, we examined the safety and tolerability of everolimus vs. placebo in de novo liver transplant recipients. One hundred and nineteen liver allograft recipients were randomized to 1 of 4 groups: everolimus 0.5 mg bid, everolimus 1.0 mg bid, everolimus 2 mg bid, or placebo. Patients received oral cyclosporine to achieve a target trough level of 150-400 ng/mL in combination with prednisone. Primary and secondary endpoints of safety, tolerability, and efficacy were determined at 12 months, and patients were followed through 36 months. There was a trend toward fewer treated acute rejections in the everolimus group than in the placebo group: everolimus 0.5 mg: 39.3%; everolimus 1.0 mg: 30.0%; everolimus 2 mg: 29.0%; placebo: 40.0% (P = not significant). Adverse events were higher in everolimus-treated patients especially at the 4-mg/day dose, but there was no difference in the incidence of thrombocytopenia or leukopenia between all groups and renal function as determined by serum creatinine, and creatinine clearance remained stable to 36 months in everolimus-treated patients. Mean cholesterol and triglycerides increased from baseline in all treatment groups, and maximum levels were seen at 6 months. In conclusion, this study demonstrates that everolimus in combination with oral cyclosporine had an acceptable safety and tolerability profile, paving the way for additional studies in this transplant indication.

Adult↗
PubMed2006

12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplant recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus.

The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neoral) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level [predose]) C0 to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85% of CsA-ME patients and 86% of tacrolimus patients survived with a functioning graft (P not significant). Efficacy was similar in deceased- and living-donor recipients. Significantly fewer hepatitis C-positive patients died or lost their graft by 12 months with CsA-ME (5/88, 6%) than with tacrolimus (14/85, 16%) (P < 0.03). Recurrence of hepatitis C virus in liver grafts was similar in each group. Based on biopsies driven by clinical events, the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME (100 +/- 50 days) than with tacrolimus (70 +/- 40 days) (P < 0.05). Median serum creatinine at 12 months was 106 mumol/L with CsA-ME and with tacrolimus. More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months (13% vs. 5%, P < 0.01). Of patients who were diabetic at baseline, more tacrolimus-treated individuals required anti-diabetic treatment at 12 months (70% vs. 49%, P = 0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months, and renal function is similar. More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline.

Age Distribution↗
PubMed2006

Medical community preferences concerning adult living related donor liver transplantation.

OBJECTIVES: To assess acceptance and acceptable estimated mortality levels for right lobe adult-to-adult living related liver transplantation for the medical and allied professions. METHODS: A paper questionnaire was sent to the physicians practicing with the French Graft Agency (Etablissement Français des Greffes) and to all nurses and ancillary staff of the Paul Brousse Hospital Hepatobiliary Center. Responses were received from surgeons: 38/73; internists specialized in hepatology: 44/120; nurses: 98/100; health care assistants: 45/86; others: 17/20. RESULTS: Acceptance of living donor transplantation is above average for all professional categories and indications may be extended including patients with cancer. Acceptable mortality for the donor was 4%, except among internists (0.7%). Currently, the real risk of mortality for the donor (1%) is lower. Acceptable mortality for the recipient was between 15 and 20%. CONCLUSIONS: Acceptance of adult living donor liver transplantation among health care professionals is clearly above average. Thus the psychological involvement of transplantation teams, which is very strong in such situations, should not hamper the development of this type of transplantation.

Adult↗
PubMed2006

[Liver transplantation for complications of hepatitis B].

In the absence of prophylaxis, there is an elevated risk of virus recurrence after liver transplantation required because of chronic hepatitis B. Regardless of prophylaxis, the risk of recurrence is associated with pre-graft viral load. Long-term prophylaxis by hepatitis B immune globulin (HBIG) significantly reduces the risk of recurrence, especially if there was no pre-graft viral replication. Use of antiviral agents such as lamivudine, adefovir, tenofovir, and entecavir, control HBV replication in patients with decompensation of cirrhosis while awaiting transplantation and in patients with HBV recurrence post-graft. The risk of emergence of resistant strains limits the use of these antiviral agents. The choice of one or several combined antiviral agents depends on their resistance profiles. Combining antiviral agents and HBIG after transplantation can reduce the risk of HBV recurrence to less than 10%, even in patients with viral replication pre-graft. If there was no detectable viral load pre-graft, withdrawal of HBIG should be considered at some point, while continuing an antiviral agent or after anti-HBV vaccination.

Adenine↗
PubMed2006

Clinical and therapeutic implications of hepatitis C virus compartmentalization.

BACKGROUND & AIMS: Blood mononuclear cells (BMCs) frequently are infected by hepatitis C virus (HCV) variants that are not found in plasma. The influence of this compartmentalization on the natural and therapeutic outcome of hepatitis C is unknown. METHODS: We studied 119 patients with previously untreated chronic HCV infection. Sixty-five of these patients started first-line treatment with pegylated interferon-alfa and ribavirin after enrollment in the study. The internal ribosomal entry site (IRES) of HCV RNA was amplified and compared between plasma and BMCs by means of single-strand conformational polymorphism (SSCP) analysis, line-probe assay, and cloning sequencing. RESULTS: The IRES SSCP patterns differed between plasma and BMCs in 54 (48%) of 113 assessable patients. Twenty-seven (24%) of these patients were co-infected by 2 HCV types or subtypes, only 1 of which was detectable in BMCs (n = 25) or in plasma (n = 2). SSCP-defined compartmentalization was more frequent in former drug users than in others (35/56 [60%] vs 19/56 [34%]; P < .01), and less frequent in patients with genotype 1 HCV in plasma (26/73 [24%] vs 28/40 [65%]; P < .01). The only variables that were independently predictive of a sustained virologic response were SSCP-defined compartmentalization (25/31 vs 10/32; P = .0001) and genotype 2 or 3 infection of BMCs (22/31 vs 8/34; P = .002). CONCLUSIONS: A significant proportion of patients with hepatitis C are co-infected by 2 or more HCV variants with distinct IRES sequences and distinct cellular tropism. This compartmentalization is a strong independent predictor of treatment efficacy.

Adult↗
PubMed2006

Aspects of hepatitis C virus infection relating to liver transplantation.

End-stage liver disease caused by the hepatitis C virus (HCV) is a major indication for liver transplantation. HCV re-infection after transplantation is almost constant, and recent data confirm that it significantly impairs patient and graft survival. Factors that may influence disease severity and consequent progression of HCV graft injury remain unclear. Chronic HCV infection develops in 75-90% of patients, and 5-30% ultimately progress to cirrhosis within 5 years. Pre-transplantation antiviral treatment is not easily related to poor tolerance. Attempts to administer prophylactic post-transplantation antiviral treatment are under evaluation but are limited by the side-effects of antiviral drugs. Treatment of established graft lesions with interferon or ribavirin as single agents has been disappointing. Combination therapy gave promising results, with sustained virological response in 25-35% of patients, but indications, modality and duration of treatment should be assessed.

Antiviral Agents↗
PubMed2006

Impact of liver transplantation on cardiac autonomic denervation in familial amyloid polyneuropathy.

Familial amyloid polyneuropathy (FAP) is a rare and severe hereditary form of amyloidosis, due to the deposition of a genetic variant transthyretin essentially produced by the liver, and characterized by both sensorimotor and autonomic neuropathy. Liver transplantation (LT) is the most effective treatment to stop the progression of the disease. Cardiac amyloid infiltration is usually associated with cardiac denervation, restrictive cardiomyopathy, conduction disturbances, and sometimes sudden death. Whether the cardiac involvement related to amyloid deposition may be altered after LT remains unclear. We conducted the present study to define the outcome of cardiac involvement after LT in 31 patients with FAP (age, 39 +/- 12 yr). Patients were evaluated before and after LT (24 +/- 15 mo). Cardiac sympathetic denervation was assessed by both iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy and heart rate variability (HRV) analysis. The scintigraphic importance of sympathetic denervation was evaluated globally on planar imaging using heart-to-mediastinum activity ratio (H/M) measured 4 hours after injection, and regionally using single-photon emission tomography (SPET) imaging. Amyloid myocardial infiltration was assessed by echocardiography. Diffuse sympathetic denervation was found when using cardiac MIBG planar imaging in patients evaluated before LT and compared with 12 control subjects (H/M: 1.45 +/- 0.29 vs. 1.98 +/- 0.35, p < 0.001). On SPET images, defects were diffuse in 12 patients and focal in 19 patients, with predominance at the inferior and apical segments. No change in sympathetic innervation was found in patients after LT as assessed either with planar imaging (H/M after LT: 1.46 +/- 0.28, p = not significant vs. H/M before LT) or with SPET imaging. HRV nonspectral indexes showed that the standard deviation of all cycles was significantly lower in patients compared with control subjects, and remained unchanged after LT. Conduction disturbances and ventricular arrhythmias were associated with low cardiac MIBG uptake, and progressed after LT. The left ventricular wall was slightly thickened in patients, and a further increase was observed after LT (posterior wall from 9.2 +/- 1.8 to 10.1 +/- 2.3 mm, p = 0.02; septal wall from 10.6 +/- 2.7 to 12.1 +/- 4, p = 0.046). Neurologic status stabilized in 26 patients, but worsened in the 5 patients who had the most severe cardiac sympathetic denervation before LT as measured by MIBG imaging. The magnitude of the cardiac sympathetic denervation remained stable 2 years after LT in patients with FAP, whereas the cardiac amyloid infiltration progressed. The importance of cardiac sympathetic denervation found in FAP patients before LT was associated with a neurologic worsening after LT.

3-Iodobenzylguanidine↗
PubMed2005

First outbreak of multidrug-resistant Klebsiella pneumoniae carrying blaVIM-1 and blaSHV-5 in a French university hospital.

OBJECTIVES: We studied eight imipenem-resistant isolates of Klebsiella pneumoniae involved in an outbreak in a French teaching hospital. METHODS: The eight isolates were recovered from clinical specimens or rectal swabs. Antibiotic susceptibilities were determined using standard agar diffusion and dilution methods including synergy tests. PFGE was used to study the relatedness of isolates. Genes encoding beta-lactamases were characterized by transfer assays, specific amplification and cloning. RESULTS: The eight isolates were closely related by PFGE analysis and highly related to a K. pneumoniae strain from Greece. They were highly resistant to beta-lactams, including aztreonam and imipenem (MIC > or =32 mg/L), and were positive by the imipenem-EDTA disc synergy test. Isolates were also resistant to aminoglycosides, newer quinolones and sulfamethoxazole, and showed an intermediate level of resistance to tetracycline. VIM-1 and SHV-5 beta-lactamases were revealed in all isolates by PCR. The analysis of plasmid contents of Escherichia coli DH10B electroporants expressing the VIM-1 beta-lactamase or the SHV-5 beta-lactamase confirmed that the two enzymes were coded by two different plasmids. The bla(VIM-1) gene was part of a class 1 integron that also included aac6, dhfrI and aadA genes and was similar to those reported from strains isolated in Greece. CONCLUSIONS: This study confirms the potential risk of spread of multiresistant bacteria with international transfer of patients.

Anti-Bacterial Agents↗
PubMed2005

Cu-Zn super oxide dismutase as a potential antifibrotic drug for hepatitis C related fibrosis.

Liver fibrosis plays a pivotal role in liver function impairment and is a feature of chronic infection by hepatitis C virus (HCV). Ten to 20% of patients progress to cirrhosis leading to an increased risk of liver failure or hepatocellular carcinoma (HCC). Recent advances have culminated in clear evidence that fibrosis can be reversible, and in expectation that effective anti-fibrotic therapy will improve the prognosis. Among the different cellular pathways involved in fibrosis, the transforming growth factor-beta1 (TGF-beta1) signaling plays a major role. Increases of TGF-beta1 expression is associated with fibrotic diseases and this cytokine could be a target for an antifibrotic drug. Clinical results on radiation-induced fibrosis have brought some evidences that Cu-Zn SOD (SOD1) could be an anti-fibrotic drug. Its therapeutic effect could be related to a down-regulation of TGF-beta1 as proved in a well characterized pig model of radiation induced fibrosis, where the efficacy of Cu-Zn SOD has been shown in reversing fibrosis. Using 3-D skin co-culture of fibroblasts from this pig model, it was showed that SOD significantly reduces the expression of the TGFbeta1, both at the mRNA and protein level. An experimental work could be undertaken to validate the Cu-Zn SOD as an anti-fibrotic drug, using HCV core protein expressing transgenic mice. As the current anti-HCV therapy with pegylated interferon combined with ribavirin can eradicate virus and stop the progression of fibrosis, but near 50% of HCV infected patients are non responders, a controlled trial is planned for HCV infected patients non responders to this therapy with a Metavir fibrosis score reaching F = 2 or >2.

Animals↗
PubMed2005

Cadaveric full-size liver transplantation and the graft alternatives in adults: a comparative study from a single centre.

BACKGROUND/AIMS: This study aims to compare the results of living donor (LDLT), cadaveric split (SLT) and domino (DO) liver transplantation which are currently available alternatives to the conventional cadaveric full-size liver transplantation (CAD). METHODS: Immunologic, vascular and biliary complications (BC) were evaluated in 38 LDLT, 20 SLT, 17 DO and 38 CAD recipients. RESULTS: The incidence of acute rejection (AR) was similar between groups, and between blood-related and blood-unrelated patients. AR was more severe in the SLT group according to the Banff scores (P=0.03, P<0.001, P<0.001). The evolution of AR was similar between the groups, in terms of development of chronic rejection. No venous complications occurred in the overall population. The rate of arterial thrombosis (10.5, 10, 0 and 3%, respectively) was statistically similar between groups. The rate of BC (26, 40, 12, and 8%, respectively) was higher in the partial grafts than in the whole grafts (P=0.006), but was not significantly different within each group. There was an association between the severity of preservation injury and occurrence of AR (P=0.01) and arterial thrombosis (P=0.016), but not BC. One- and 2-year graft and patient survival rates were similar between groups. CONCLUSIONS: None of the graft types seemed to confer immunological advantage. BC remained problematic in the partial grafts, independently from ischemia time.

Adult↗
PubMed2005

Treatment of hepatitis B and C after liver transplantation. Part 1, hepatitis B.

The outcome of OLT for HBV-related liver disease is dependent on the prevention of allograft re-infection. Over the past decade, major advances have been made in the management of HBV transplant candidates. The advent of long-term hepatitis B immune globulin (HBIG) administration as a prophylaxis against HBV recurrence, and the introduction of new antiviral agents against HBV infection, such as lamivudine (LAM), were a major breakthrough in the management of these patients. Results of OLT for HBV infection are similar to those achieved with other indications. Pre-OLT antiviral treatment such as LAM can suppress HBV replication before OLT and thus decrease the risk of re-infection of the graft. Combination prophylaxis with LAM and HBIG after transplantation highly effectively reduces the rate of HBV re-infection, even in HBV replicative cirrhotic patients. The optimal HBIG protocol in the LAM era is yet to be defined: dosing of HBIG, routes of administration, and possibility of stopping HBIG. Several antiviral drugs have been developed for the management of HBV infection on the graft, so outcome is currently good.

Antiviral Agents↗