Showing papers by "Didier Samuel published in 2007"
TL;DR: In conclusion, corticosteroid therapy is of little benefit in severe and fulminant forms of AIH; it may favor septic complications and should not delay LT.
211 citations
TL;DR: The results of liver transplantation in HIV‐HCV–coinfected patients were satisfactory in terms of survival benefit, and earlier referral of these patients to a liver transplant unit, the use of new drugs effective against HCV, and an avoidance of drug toxicity are mandatory to improve the results of this challenging indication for liver transplation.
191 citations
TL;DR: No single factor but a combination of several factors is associated with fibrosis progression on the graft and how these could be modified to improve outcome of recurrent hepatitis C.
Abstract: Hepatitis C virus (HCV)-related end-stage liver disease is the main indication for liver transplantation performed in Europe and the United States. Recurrence of hepatitis C in the graft is universal and may lead to chronic hepatitis in most patients and to cirrhosis in 20-30% of patients within 5-10 years of transplantation. The natural history of HCV recurrence is highly variable but leads to a lower survival rate than other recurrent liver diseases. The immunosuppressed status and several other factors have been linked with the pattern and severity of recurrence. What remains controversial are those factors associated with fibrosis progression and how these could be modified to improve outcome of recurrent hepatitis C. No single factor but a combination of several factors is associated with fibrosis progression on the graft. The major factors associated with accelerated disease recurrence include: high viral load pre- (>10(6) IU / mL) and / or early post-transplantation (>10(7) IU / mL at 4 months), donor older than 40-50 years, prolonged ischaemic time, cytomegalovirus coinfection, over immunosuppression and / or abrupt changes in immunosuppression, HIV coinfection, infection by genotype 1b. Cautious follow-up of the pathology of the graft is mandatory including routine biopsies and / or noninvasive monitoring of fibrosis.
95 citations
TL;DR: This study, which represents the largest published experience with the surgical treatment of patients with symptomatic portal biliopathy, indicates that retroperitoneal splenorenal anastomosis improves outcomes and should be the initial treatment of choice.
Abstract: A portal cavernoma (PC) or a cavernous transformation of the portal vein is a concentrated vascular system composed of dilated periportal veins within the hepatic pedicle.1 This venous abnormality develops from chronic obstruction of the distal portal vein in a compensatory effort to maintain hepatofugal flow. The magnitude of PC is related to the extent of portal thrombosis. Typically, the livers of patients with PC are otherwise normal.
In the absence of abdominal surgery, where PC may lead to significant intraoperative hemorrhage, this abnormality is generally asymptomatic.2,3 However, within the hepatic pedicle dilatation of veins around and inside the bile duct wall can impact on the adjacent biliary ducts.4 Indeed, the majority of patients with PC will develop morphologic biliary abnormalities, termed “portal biliopathy.”5 Portal biliopathy may lead to asymptomatic cholestasis in half of patients; and more rarely, it can cause symptomatic biliary obstruction.6
The development of symptomatic portal biliopathy from PC poses a difficult therapeutic problem, as the PC is frequently a significant obstacle to treatment of the biliary obstruction. Furthermore, there are very few reports in the literature describing the treatment of portal biliopathy and even fewer with long-term outcome analyses. The aim of this study, therefore, was to report our therapeutic strategies and long-term results following the treatment of 19 patients with PC complicated by symptomatic biliary obstruction.
69 citations
TL;DR: The lopinavir/ritonavir combination markedly inhibited tacrolimus metabolism, whereas the effect of efavirenz was small, and tacro Limus dosing must be optimised according to therapeutic drug monitoring and the antiretroviral drug combination.
Abstract: To characterise the interactions between tacrolimus and antiretroviral drug combinations in hepatitis C virus-HIV co-infected patients who had received a liver transplant. An observational, open-label, multiple-dose, two-period, one-sequence design clinical trial in which patients received tacrolimus as an immunosuppressive therapy during the postoperative period and then had an antiretroviral drug regimen added. Tacrolimus pharmacokinetics were evaluated at steady state during these two periods. Fourteen patients participated in the study and seven participated in the intensified pharmacokinetic protocol. Patients were included if they had undergone liver transplantation for end-stage chronic hepatitis C, absence of opportunistic infection, a CD4 cell count of >150 cells/μL and an undetectable HIV plasma viral load (<50 copies/mL) under highly active antiretroviral therapy. During the posttransplantation period, the tacrolimus dose was adjusted according to blood concentrations. When liver function and the tacrolimus dose were stable, antiretroviral therapy was reintroduced. When lopinavir/ritonavir were added to the tacrolimus regimen (seven patients), the tacrolimus dose was reduced by 99% to maintain the tacrolimus concentration within the therapeutic range. Only two patients were treated with nelfinavir, which led to a wide variation in inhibition of tacrolimus metabolism. When efavirenz (four patients) or a nucleoside analogue combination (one patient) was added, very little change in tacrolimus dosing was required. The lopinavir/ritonavir combination markedly inhibited tacrolimus metabolism, whereas the effect of efavirenz was small. Tacrolimus dosing must be optimised according to therapeutic drug monitoring and the antiretroviral drug combination.
62 citations
TL;DR: In liver recipients with CRF, a reduction or withdrawal of CNI concomitantly with the introduction of MMF was safe and was associated with an improvement in renal function and three parameters were identified as risk factors for unresponsiveness to CNI reduction.
50 citations
TL;DR: In tumoral hepatocytes, low‐replicating hepatitis C quasispecies are compartmentalized and more diversified and are subjected to low selective pressure, which supports the importance of core genetic variability in hepatocellular carcinogenesis.
47 citations
TL;DR: Most MHR variants emerge with longer disease duration and upon indirect selective pressure, andVariation of the MHR may serve to restore virus replication of resistant strains.
Abstract: BACKGROUND: Understanding the prevalence of potential antigenic variation of the hepatitis B virus (HBV) surface antigen (HBsAg) is fundamental for assay design and to future changes in vaccine formulation. In this study, the nature and frequency of HBsAg polymorphisms occurring in France in chronic carriers and in newly diagnosed patients were determined. We focused on variations in the major hydrophilic region (MHR), the central core of HBsAg known to be exposed on the surface and involved in antibody binding. METHODS: Two patient groups were identified: 51 chronic HBV carriers followed at our institution for > 1 year; and 129 newly diagnosed patients (63 of whom had a first HBsAg-positive result at our hospital laboratory and 66 a first positive result in a private laboratory). DNA sequences of HBsAg were obtained from these 180 patients and compared with consensus sequences built with 168 full-length HBV sequences imported from GenBank. Polymorphisms of the MHR of HBsAg were analysed with the Mutation Master Software. Literature review and BLOSUM scores were used to define potentially altered antigenicity. RESULTS: The global frequency of MHR variants was 27.8%. Occurrence of MHR variants was independent of viral load, HBeAg status and sex, but was associated with the chronic carriers' group, advancing age, the presence of antibodies to HBsAg, immunoprophylaxis administration, antiviral treatment and genotypic resistance to antivirals. In multivariate analysis, the independent variables associated with MHR variants were advancing age and the presence of genotypic resistance to nucleoside or nucleotide analogues. CONCLUSION: Most MHR variants emerge with longer disease duration and upon indirect selective pressure. Variation of the MHR may serve to restore virus replication of resistant strains. Combined envelope and polymerase variants could impair diagnostic assays and limit treatment alternatives.
31 citations
TL;DR: A significant proportion of human cholangiocarcinomas expresses membrane sodium iodide symporter, which may permit radioiodine therapy, and data suggest that (131)I acts on a crucial target for liver cancer development.
27 citations
TL;DR: The benefit of neoadjuvant TACE may be limited to those patients transplanted from 4 to 9 months from first TACE, and data may help transplant programs to tailor TACE treatments based on predicted waitlist times to achieve optimal resource utilization and improved organ allocation efficiency.
26 citations
TL;DR: This is the first report of proteasome and carbonic anhydrase III as autoantigens in de novo AIH, which could lead to a better diagnosis of this disease using identified autoantIGens in diagnostic tests, and strengthen proteomic approach as a new way of autoantigen investigation.
Abstract: De novo autoimmune hepatitis (AIH) occurs after liver transplantation for nonautoimmune disorders. Autoantibodies so-called atypical anti-liver/kidney microsome antibodies (LKMA) with an unusual liver/kidney cytoplasmic staining as judged by indirect immunofluorescence, can be detected in some patients' sera. Few studies investigated their molecular targets, and the aim of this work was to identify the atypical anti-LKMA targets by proteomic tool. This proteomic approach consisted of (a) two-dimensional gel electrophoresis of cytosolic and microsomal proteins obtained by differential centrifugations of rat liver and rat kidney, followed by (b) two-dimensional immunoblotting with sera of patients with de novo AIH (n = 8, including 2 with anti-LKMA antibodies) and then (c) identifications of interest spots performed by ion trap mass spectrometry. By this way several proteins at 25 kDa were unambiguously identified: isoforms of carbonic anhydrase III, members of different glutathione S-transferase (GST) families, and subunit beta1 of proteasome. This is the first report of proteasome and carbonic anhydrase III as autoantigens in de novo AIH. These results could lead to a better diagnosis of this disease using identified autoantigens in diagnostic tests, and strengthen proteomic approach as a new way of autoantigens investigation.
Journal Article•
TL;DR: During the past 3 decades, more than 2,250 liver transplants were performed at Paul Brousse Hospital, overall patient survival was 82% at one year, 71% at 5 years and 64% at 10 years, with main problem was HCV recurrence which was more severe in HIV co-infected patients.
Abstract: During the past 3 decades, more than 2,250 liver transplants were performed at Paul Brousse Hospital. Overall patient survival was 82% at one year, 71% at 5 years and 64% at 10 years. Our group has developed a variety of approaches to liver transplantation, including: 1. Anti HBs immunoglobulin prophylaxis for the prevention of HBV recurrence. Combination prophylaxis with lamivudine and anti HBs immunoglobulins reduced the rate of HBV re-infection to 20%. 2. Transplantation of HIV-HCV and HIV-HBV infected patients. These transplants are feasible and we achieved 2- year survival rates of 70% and 90%, respectively. The main problem was HCV recurrence which was more severe in HIV co-infected patients. 3. Transplantation for hepatocellular carcinoma on a cirrhotic liver with a single tumor <5 cm or <3 tumors <3 cm. 4. Transplantation for familial amyloidotic polyneuropathy (FAP). The 5- and 10-year survival rates were 76% and 72%, respectively. More than 100 livers obtained after hepatectomy from FAP patients were transplanted as "domino" living donor livers to patients with unresectable liver cancers with a 5-year survival rate of 64%. In some domino recipients, symptoms of FAP disease occurred more rapidly than expected and this could be an indication for a second transplantation of a non FAP-liver. 5. Split-liver transplantation for pediatric patients. This has increased the number of transplantable livers for children by 28%. 6. Split-liver transplantation for 2 adults. The grafts were prepared by ex-vivo or in-situ splitting and the overall 5-year survival rate was 56%. 7. Adult -to-adult living-related liver transplantation. There has been no mortality nor late complications in donors and the overall 5-year survival rate among recipients was 73%. 8. Liver retransplantation with good results in the elective situation. Retransplantation should be used with discretion in the emergency setting.
Journal Article•
TL;DR: Prospective and retrospective studies indicate a significant trend towards reduced incidence of HCC in patients receiving long term interferon therapy, and it is critical for the moment to protect as many patients as possible from irreversible deterioration.
Abstract: Therapy of chronic hepatitis C presently achieves 60% of sustained virological response, with clear on improvement of liver histology. Failure to eradicate HCV infection does not mean that the patient is non-responsive to therapy and indeed most patients improve biochemically and histologically. The objective of maintenance therapy is therefore to reduce fibrosis progression and its complications. Meta-analysis of 4 registration pivotal trials revealed that 40% of patients who failed to clear HCV at the end of therapy, improved histologically. 3 large long term prospective studies in mostly advanced patients have also addressed the issue of maintenance therapy: HALT-C, COPILOT, EPIC 3. Interim analysis at 2 years of the COPILOT study in particular reveals that only 20% patients receiving low dose peg-interferon versus 39% in the placebo colchicine group reached complication end points. Prospective and retrospective studies, controlled or not, do also indicate a significant trend towards reduced incidence of HCC in patients receiving long term interferon therapy. Potent new anti-HCV small molecules will soon become available and will undoubtedly increase dramatically the cure rate. It is critical therefore for the moment to protect as many patients as possible from irreversible deterioration.
TL;DR: Current experience in liver and liver-kidney transplantation, the mechanism of tolerance and the immunosuppressive strategy used in liver transplantation are described and decreased in an attempt to limit side effects and the direct toxicity of calcineurin inhibitor for kidney function.
TL;DR: It has been suggested that, in this particular context, the course of HCV graft disease is accelerated in transplant recipients compared to immune competent patients, resulting in an excess risk of death or re-transplantation for liver failure at 10–15 years posttransplant.
TL;DR: This disease is a more general disease with an autonomic neuropathy with postural hypotension, sexual impotence in men, alternating diarrhoea‐constipation, dysuria and urinary incontinence, and is mainly characterized by a sensory-motor length-dependent polyneuropathy affecting first the lower limbs and then the upper limbs.
Abstract: In 1991, a Swedish group proposed liver transplantation as the treatment of familial amyloidotic polyneuropathy (FAP) [1]. This was a therapeutic breakthrough. Until that time, FAP was a devastating disease leading patients to death in a median of 10 years after appearance of the first symptoms. No medical treatment has been shown to slow down the progression of the disease. The disease is secondary to a point mutation in the gene coding for the production of transthyretin, located on the chromosome 18. Transthyretin is a protein synthesized at 90‐98% by the liver. The disease is a hereditary dominant transmitted disease. The point mutation of the gene coding for transthyretin leads to a disruption of the thransthyretin protein in amyloid fibrils. The symptoms are mainly characterized by a sensory-motor length-dependent polyneuropathy affecting first the lower limbs and then the upper limbs. This disease is, in fact, a more general disease with an autonomic neuropathy with postural hypotension, sexual impotence in men, alternating diarrhoea‐constipation, dysuria and urinary incontinence. Amyloid deposits are present in the cardiac muscle leading to amyloid restrictive cardiomyopathy with conduction troubles, and are present in renal glomeruli leading to amyloid glomerulonephritis. Finally, deposits can be found in the vitreum reducing visual ability. The most
TL;DR: L’infection par le virus de l’immunodeficience humaine (VIH) a longtemps ete consideree comme une contre-indication a la transplantation hepatique, d’un nombre important de patients developpent une cirrhose menacant le pronostic vital.
Abstract: L’infection par le virus de l’immunodeficience humaine (VIH) a longtemps ete consideree comme une contre-indication a la transplantation hepatique. Les raisons en etaient le pronostic sombre lie a la maladie VIH. L’avenement des tritherapies antiretrovirales a revolutionne le traitement des patients infectes par le VIH. Trente pour cent et 10 % des patients infectes par le VIH sont egalement infectes respectivement par le virus de l’hepatite C (VHC) et par le virus de l’hepatite B (VHB). L’hepatite chronique C et B semble progresser plus vite chez les patients co-infectes et un nombre important de patients developpent une cirrhose menacant le pronostic vital. La transplantation hepatique pose plusieurs problemes dans ce contexte : (1) le risque d’accident d’exposition au sang lors de cette intervention longue et hemorragique ; (2) le moment de l’indication de la transplantation ; (3) l’interference entre les antiretroviraux et les inhibiteurs de la calcineurine ; (4) le risque de recidive du VHB ou du VHC. Depuis 1999, un programme de transplantation hepatique chez les patients co-infectes a demarre avec le soutien de l’Agence nationale de recherche contre le sida et les hepatites. Les premiers resultats montrent une survie a 2 ans de 70 % des patients infectes par le VHC et de 100 % des patients infectes par le VHB. Il n’a pas ete note de progression acceleree de la maladie VIH. La recidive virale B est bien prevenue par l’association post-transplantation d’immunoglobulines specifiques anti-HBs et d’analogues nucleosidiques et nucleotidiques efficaces contre le VHB. La difficulte majeure est la recidive virale C. L’identification de ses mecanismes, sa prevention et son traitement sont les futurs defis a resoudre.
TL;DR: Didier Samuel and Anne Marie Roque-Afonso Institut National de la Sante et de the Recherche Medicale (INSERM) and Universite Paris-Sud, UMR-S785, Villejuif, France.
TL;DR: La non-eradication du VHC ne signifie en aucun cas que le patient ne beneficie pas du traitement and, en fait, une proportion significative des malades ameliore leurs transaminases et leur histologie.
Abstract: Resume Tous patients confondus, le traitement de l’hepatite chronique C par bitherapie pegylee permet actuellement d’obtenir 60 % de reponse virologique durable. Cette reponse virologique s’associe a une amelioration histologique. La non-eradication du VHC ne signifie en aucun cas que le patient ne beneficie pas du traitement et, en fait, une proportion significative des malades ameliore leurs transaminases et leur histologie. L’objectif du traitement d’entretien est de reduire la progression de la fibrose et ses complications, cirrhose et cancer. La meta-analyse de 4 etudes pivots a montre que 40 % des patients n’ayant pas elimine le VHC a la fin du traitement avaient une amelioration histologique. Trois vastes essais prospectifs chez des patients evolues ont pour objectif de documenter le benefice d’un traitement d’entretien (HALT-C, COPILOT, EPIC3). Les resultats a deux ans de l’etude COPILOT sont particulierement eloquents, puisque 20 % seulement des patients recevant de l’interferon pegyle ont atteint les criteres de complication, contre 40 % des malades controles. Dans un futur proche (a partir de 2010), de nouvelles molecules antivirales specifiques seront disponibles. Elles vont augmenter dramatiquement le pourcentage de guerison. Il est donc essentiel actuellement d’eviter au plus grand nombre de malades possible de progresser vers les complications hepatiques irreversibles.