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Biomedical subjects

Didier Samuel

Publications and source records attributed to Didier Samuel.

At least 55 records · Page 3Linked to original sources
PubMed2004

Fatal disseminated Kaposi's sarcoma following human herpesvirus 8 primary infections in liver-transplant recipients.

Human herpesvirus 8 (HHV-8) is associated with the development of Kaposi's sarcoma (KS) and rare lymphoproliferative disorders in immunosuppressed patients. The risk of HHV-8 transmission by liver transplantation and the clinical manifestations of primary infection in this setting have yet to be determined. In order to evaluate this risk, we measured the seroprevalence of HHV-8 among 122 liver donors and their respective recipients before and after transplantation. Molecular methods and immunohistochemical analyses were performed to study the features of HHV-8 infection. Antibodies to HHV-8 were detected in sera of 4 donors before transplantation (3.3%) and of 3 recipients (2.4%). None of the 3 recipients, who were HHV-8 seropositive before transplantation, developed a KS during the follow-up. Four primary HHV-8 infections were detected among the 4 HHV-8 seronegative recipients who received a liver from an HHV-8 positive donor. Among these 4 recipients, 2 particularly immunosuppressed patients developed symptomatic diseases and died a few months after transplantation, harboring disseminated KS and HHV-8 positive lymphoproliferation. In these 2 patients, HHV-8 DNA genome sequences were detectable in peripheral blood mononuclear cells and other tissues with high viremia levels before and at the beginning of HHV-8-related diseases. In conclusion, in liver transplantation recipients, HHV-8 primary infection can be associated with fatal outcome. This study raises the question of screening liver donors for HHV-8--even in low HHV-8 infection prevalence countries--not systematically to exclude the graft but to monitor, clinically and biologically, patients who received a graft from an HHV-8-infected donor.

Adolescent↗
PubMed2004

Evolving strategies to prevent HBV recurrence.

1. Long-term prophylaxis with hepatitis B immune globulin (HBIG) significantly reduces the risk for hepatitis B virus (HBV) recurrence and increases survival. Patients with HBV cirrhosis and / or positive HBV DNA at the time of transplantation have a high risk for recurrence despite HBIG prophylaxis. 2. Pre-orthotopic liver transplantation (OLT) antiviral treatment using lamivudine (LAM) can suppress HBV replication before transplantation and may induce clinical improvement in a subset of patients. Adefovir dipivoxil (ADV) may serve as "rescue" therapy for patients with LAM resistance; its place as first-line therapy requires further evaluation. 3. Combination prophylaxis with LAM and HBIG prevents HBV recurrence in 90% to 100% of patients who undergo transplantation for hepatitis B. The optimal HBIG protocol in the "nucleoside-nucleotide analog era" remains to be determined. The place of ADV or LAM as first-line posttransplant antiviral therapy in combination with HBIG requires further studies. 4. Future research should test new protocols using lower HBIG doses given intravenously (IV) or intramuscularly (IM) alone or in combination with antiviral agents and identify patients in whom HBIG prophylaxis can be stopped safely or replaced by antiviral agents or vaccination.

Antiviral Agents↗
PubMed2004

Steroid withdrawal at day 14 after liver transplantation: a double-blind, placebo-controlled study.

Some clinical studies in liver transplantation have recently reported safety advantages and similar acute rejection rates with early steroid withdrawal. The aim of this study was to evaluate the efficacy and safety of an immunosuppressive regimen with steroid withdrawal at day 14. A multicenter, 1-year, comparative, double blind, placebo-controlled study was performed. Patients undergoing a first cadaveric liver transplantation were recruited and all received basiliximab + cyclosporine + intravenous methylprednisolone. Patients without severe postoperative complications were randomized at day 7 to receive a maintenance regimen with Neoral (cyclosporine) + prednisolone (group 1) or without steroids (Neoral + placebo; group 2), after a 7-day blinded oral steroid tapering period. A total of 174 patients were randomized at day 7 (group 1: n = 90; group 2: n = 84). The incidence of biopsy-confirmed and treated acute rejection at 6 months was 38.1% in group 2 vs. 24.4% in group 1 (P = .03) with a trend for a higher incidence of Grade II / III acute rejection (28.6% vs. 18.9%; P = .12). Changes from baseline were similar with regard to metabolic parameters (glycemia, total cholesterol, and triglycerides). A trend toward a better glucose tolerance was observed, as fewer patients received an antidiabetic treatment in the placebo group (2 vs. 10). In conclusion, this first double-blind, placebo-controlled study of steroid withdrawal at day 14 showed a higher incidence of acute rejection, only balanced by a trend of a lower need of antidiabetic treatment.

Adult↗
PubMed2004

Heterogeneous nuclear ribonucleoprotein A2/B1 identified as an autoantigen in autoimmune hepatitis by proteome analysis.

Our aim was to characterize antinuclear antibody (ANA) targets in type 1 autoimmune hepatitis (AIH1) using a proteomic tool. ANA-positive sera from 29 patients with AIH1 and 14 negative controls were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. The principal antigens identified were a 30 kDa triplet band which was recognized by 79% of patient sera and 14% of control sera, and a 36 kDa antigen which was recognized by 52% and 14% of sera, respectively. The latter antigen was studied in more detail using two-dimensional electrophoresis (2-DE) and mass spectrometry (MS). Its identification corresponded to heterogeneous nuclear ribonucleoprotein A2/B1. This paper presents the first description of this protein as an antigen in AIH1.

Adolescent↗
PubMed2004

Donor age influences 10-year liver graft histology independently of hepatitis C virus infection.

BACKGROUND/AIMS: Factors influencing the long-term histological outcome of liver graft are not known. We conducted a prospective study based on a 10-year liver biopsy in order to identify the main factors influencing long-term graft histology. METHODS: 270 of 423 patients who still had their first functional graft 10 years after liver transplantation accepted to undergo routine liver biopsy. All slides were blindly reviewed by two pathologists. RESULTS: Main histological findings were fibrosis in 143 patients (54%) and ductopenia in 76 patients (29%). Ductopenia was independently related to higher donor age (32+/-12 vs 28+/-13 years; P<0.02). Severity of fibrosis was influenced by hepatitis C virus (HCV) infection (P<0.001), hepatitis B virus (HBV) recurrence (P=0.001) and higher donor age (P=0.03). Eighty biopsies (30%) showed minimal-change lesions which were associated with the absence of HCV infection (24/80 vs 99/185; P<0.001) or of HBV infection (1/80 vs 15/185; P=0.03) and lower donor age (25+/-11 vs 31+/-13 years; P<0.001). CONCLUSIONS: Post-transplant infection by HCV or HBV are main factors influencing the histological course of liver graft. Donor age was also a strong factor in HCV infected patients as well as in HCV-negative patients. This variable should be taken into account, particularly for candidate recipients with long life expectancy.

Adult↗
PubMed2004

Treatment of patients with hepatic failure: the difficult place of liver support systems.

UNLABELLED: Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure. Demetriou AA, Brown RS Jr, Busuttil RW, Fair J, McGuire BM, Rosenthal P, Am Esch JS 2nd, Lerut J, Nyberg SL, Salizzoni M, Fagan EA, de Hemptinne B, Broelsch CE, Muraca M, Salmeron JM, Rabkin JM, Metselaar HJ, Pratt D, De La Mata M, McChesney LP, Everson GT, Lavin PT, Stevens AC, Pitkin Z, Solomon BA. Liver Support Unit, Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite 8215, North Tower, Los Angeles, CA 90048, USA. OBJECTIVE: The HepatAssist liver support system is an extracorporeal porcine hepatocyte-based bioartificial liver (BAL). The safety and efficacy of the BAL were evaluated in a prospective, randomized, controlled, multicenter trial in patients with severe acute liver failure. SUMMARY BACKGROUND DATA: In experimental animals with acute liver failure, we demonstrated beneficial effects of the BAL. Similarly, Phase I trials of the BAL in acute liver failure patients yielded promising results. METHODS: A total of 171 patients (86 control and 85 BAL) were enrolled. Patients with fulminant/subfulminant hepatic failure and primary nonfunction following liver transplantation were included. Data were analyzed with and without accounting for the following confounding factors: liver transplantation, time to transplant, disease etiology, disease severity, and treatment site. RESULTS: For the entire patient population, survival at 30 days was 71% for BAL versus 62% for control (P=0.26). After exclusion of primary nonfunction patients, survival was 73% for BAL versus 59% for control (n=147; P=0.12). When survival was analyzed accounting for confounding factors, in the entire patient population, there was no difference between the 2 groups (risk ratio=0.67; P=0.13). However, survival in fulminant/subfulminant hepatic failure patients was significantly higher in the BAL compared with the control group (risk ratio=0.56; P=0.048). CONCLUSIONS: This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure. [Abstract reproduced by permission of Ann Surg 2004;239:660-667; discussion 667-670].

Clinical Trial↗
PubMed2004

Management of hepatitis B in liver transplantation patients.

The success of orthotopic liver transplantation for patients with hepatitis B virus (HBV) disease has been compromised by reinfection. Prophylaxis has dramatically lowered the rate of reinfection and increased patient survival. Long-term treatment with hepatitis B immunoglobulin (HBIg), although expensive, is effective. New antiviral nucleoside analogs have also been evaluated. In patients with cirrhosis and replicative HBV infection, lamivudine before transplantation and in combination with HBIg post transplantation reduces reinfection, but the rate of resistance mutation is rather high, reaching 25% at 2 years. Adefovir has been used as a rescue therapy and prior to transplantation in lamivudine-resistant patients, significantly improving liver function and reducing HBV DNA levels. Patients with active viral replication should receive preoperative antiviral therapy with lamivudine. HBIg therapy may be discontinued in selected patients after transplantation, albeit with caution, because low levels of HBV DNA have persisted. Antiviral therapy has improved the prognosis after graft infection.

Adenine↗
PubMed2003

Quality of life in adult survivors beyond 10 years after liver, kidney, and heart transplantation.

BACKGROUND: The yearly increasing survival rates testify to the success of transplantation, but questions remain relating to the quality of life (QOL) associated with long-term survival. METHODS: A sample of 126 liver recipients (Liver-R), 229 kidney recipients (Kidney-R), and 113 heart recipients (Heart-R) with more than 10 years posttransplant follow-up were included in the study with a response rate of 86%. Respondents were matched with healthy subjects recruited from general population (GP). The three groups of recipients and GP subjects completed a French version of the questionnaire used by the National Institute of Diabetes and Digestive and Kidney Disease, Pittsburgh, PA, and were compared for each score, with adjustments for age and sex. RESULTS: Personal function and measures of disease by the transplant recipients were significantly worse than in the GP (P<0.0001), with the worst score in Kidney-R. No difference, either between organs or between organs and GP, was found regarding the perceived social and role function. However, for psychologic status and general health perception, Kidney-R had the least favorable performance when compared with GP (P<0.01) and also when compared with Liver-R (P<0.05). With the exception of Kidney-R, the well-being index of Liver-R and Heart-R was significantly better than the GP (P<0.001 and P<0.05, respectively). CONCLUSIONS: The QOL beyond 10 years after liver, heart, and kidney transplantation is quite similar to the GP, with Kidney-R starting out as the worst, Heart-R as intermediate, and Liver-R the best.

Adolescent↗
PubMed2003

Adefovir dipivoxil therapy for lamivudine-resistant hepatitis B in pre- and post-liver transplantation patients.

Three-hundred and twenty-four patients were enrolled in an open-label, multicenter, international study in which pre- and post-liver transplantation (LT) patients with recurrent chronic hepatitis B (CHB) and evidence of lamivudine-resistant HBV were treated with adefovir dipivoxil 10 mg once daily. In the pre- and post-LT cohorts, 128 and 196 patients were treated for a median duration of 18.7 and 56.1 weeks, respectively. In patients who received 48 weeks of treatment, 81% of the pre-LT and 34% of the post-LT cohort achieved undetectable serum hepatitis B virus (HBV) DNA (Roche Amplicor Monitor polymerase chain reaction [PCR] assay lower limit of quantification [LLQ] < 400 copies/mL) with a median change in serum HBV DNA from baseline of -4.1 log(10) and -4.3 log(10) copies/mL, respectively. Serum alanine aminotransferase (ALT), albumin, bilirubin, and prothrombin time normalized in 76%, 81%, 50%, and 83% of pre-LT patients and 49%, 76%, 75%, and 20% of post-LT patients. The Child-Pugh-Turcotte (CPT) score improved in over 90% of patients in both cohorts. Genotypic analysis of 122 HBV baseline samples revealed that 98% of these patients had lamivudine-resistant mutant HBV. No adefovir resistance mutations were identified in patients after 48 weeks of therapy. One-year survival was 84% for pre-LT and 93% for post-LT patients (Kaplan-Meier analysis). Treatment-related adverse effects associated with adefovir dipivoxil in this setting were primarily mild to moderate in severity. In conclusion, 48 weeks of adefovir dipivoxil resulted in significant improvements in virologic, biochemical, and clinical parameters in CHB patients pre- and post-LT with lamivudine-resistant HBV.

Adenine↗
PubMed2003

Human leukocyte antigen-G (HLA-G) expression in biliary epithelial cells is associated with allograft acceptance in liver-kidney transplantation.

BACKGROUND/AIMS: Liver allograft is known to protect simultaneously transplanted organs from acute rejection. We have reported that only 6% of combined liver-kidney recipients, versus 32.5% of kidney recipients, develop kidney graft acute rejection. Release of soluble human leukocyte antigen (HLA) molecules by the liver has been proposed as a possible tolerogenic mechanism involved in the better acceptance of double transplants. The HLA-G molecule is acknowledged to possess tolerogenic properties. METHODS: We investigated the involvement of HLA-G in allogeneic transplant acceptance by analyzing its expression in kidney and liver biopsies of 40 combined transplanted patients. RESULTS: We demonstrate the presence of HLA-G in 14 out of 40 liver and five out of nine kidney transplants biopsies. HLA-G is expressed de novo by cells that are otherwise frequently susceptible target cells of acute rejection, i.e. liver biliary and renal tubular epithelial cells. We show a significant association between HLA-G expression in liver biliary epithelial cells and the absence of liver graft rejection. No acute or chronic rejection of the kidney graft was observed in patients in whom HLA-G was expressed in the liver graft. CONCLUSIONS: HLA-G expression in the liver allograft is associated with a lower frequency of hepatic and renal acute rejection and may be involved in the acceptance of simultaneously transplanted organs.

Adult↗
PubMed2003

Immunosuppression in hepatitis B virus and hepatitis C virus transplants: special considerations.

The management of the immunosuppression treatment must take account its consequences on viral replication. Such treatment operates on the emerging balance between the recurrence of the virus on the graft and the immune response of the host. Randomized and prospective trials are currently ongoing with the purpose of determining the opportunity and relevance of each immunosuppressive agent in the treatment. In HBV patients, good control of HBV reinfection by prophylactic strategies using HBIG, lamivudine, or both have decreased the impact of immunosuppression on HBV recurrence. In contrast, HCV recurrence is now a major problem. The mechanisms of viral recurrence need to be deepened thus requiring new studies. The absence of in vitro and in vivo systems to study HCV reinfection is a lack in the comprehension of the relation between HCV and immunosuppression. It will allow adapting the effectiveness of the immunosuppression treatment. The treatment's primary target is to avoid graft rejection, and its secondary objective is to limit the risk of viral recurrence.

Graft Rejection↗