Search PubMed⌕ Search

Biomedical subjects

J Lerut

Publications and source records attributed to J Lerut.

At least 19 recordsLinked to original sources
PubMed2006

Living-related versus deceased donor pediatric liver transplantation: a multivariate analysis of technical and immunological complications in 235 recipients.

Timely access to a living donor (LD) reduced pretransplant mortality in pediatric liver transplantation (LT). We hypothesized that this strategy may provide better posttransplant outcome. Between July 1993 and April 2002, 235 children received a primary LT from a LD (n = 100) or a deceased donor (DD) (n = 135). Demographic, surgical and immunological variables were compared, and respective impact on posttransplant complications was studied using a multivariate analysis. Five-year patient survival rates were 92% and 85% for groups LD and DD, respectively (p = 0.181), the corresponding graft survival rates being 89% and 77% (p = 0.033). At multivariate analysis: (1) type of donor (DD) was correlated with higher rate of artery thrombosis (p < 0.012); (2) biliary complication rate at 5 years was 29% and 23% for groups LD and DD, respectively (p = 0.451); (3) lower acute rejection incidence could be correlated with type of donor (DD) (p = 0.001), and immunosuppressive therapy (tacrolimus) (p < 0.001). We conclude that (1) according to the multivariate analysis, LT with LD provided similar patient and graft outcome, when compared to DD; (2) a higher rate of artery thrombosis and a lower rate of rejection were observed in group DD; (3) this study confirms the efficacy of tacrolimus for immunoprophylaxis, whatever the type of organ donor is.

Adolescent↗
PubMed2006

An appraisal of tolerance in liver transplantation.

Human liver allografts have a lower susceptibility to rejection than other organs. In addition, in some liver transplant recipients immunosuppressive drugs can be completely withdrawn, and these patients are considered as 'operationally' tolerant. Careful scrutiny of accumulated clinical experience indicates that elective immunosuppressive drug weaning is feasible in almost 20% of selected liver transplant recipients. This is associated with an incidence of 12% to 76% of acute cellular rejection, but these episodes are commonly mild and often resolve by return to baseline immunosuppression (IS), many times without the need to administer steroid boluses. Study of tolerance in liver transplantation (LT) has been hampered by confusion regarding the definitions of rejection and tolerance, and by the absence of prospective studies correlating results of immune monitoring assays and clinical outcome. Thus, we lack a clinically validated treatment-stopping rule capable of predicting the success of IS withdrawal and this procedure has to be performed on a 'trial and error' basis. The search for an accurate means to identify allograft tolerance among immunosuppressed recipients should become a priority in LT research. This information would provide a biological basis for guiding IS withdrawal protocols and for the implementation of tolerance-promoting strategies in LT.

Animals↗
PubMed2001

Use of mycophenolate mofetil as rescue therapy after pediatric liver transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) has been increasingly used after liver transplantation (LT) in adults. We report our preliminary experience with MMF as rescue therapy after pediatric LT. METHODS: A total of 19 children received MMF for 21 indications. Median age at LT was 30 months (range 7-149). The median initial oral dose of MMF was 23 mg/kg/day (range 12-43) orally. Median follow-up after initiation of MMF therapy was 642 days (range 229-1606). RESULTS: 1) EFFICACY: MMF was indicated for rejection or insufficient immunosuppression in 16 cases, with normalization of both liver function tests and liver histology in 10 (62%). MMF was successfully used in one patient with post-LT immmune hepatitis and one patient with corticodependence. In three patients with renal function impairment, MMF allowed reduction of cyclosporine A or tacrolimus blood levels, without subsequent rejection. 2) Tolerance: Six patients (32%) experienced eight side effects, mainly gastrointestinal and hematological, which resolved after cessation of MMF in five cases and dose reduction in three. One case of posttransplant lymphoproliferative disease (PTLD) occurred under MMF therapy (5.2%). Four patients had EBV primary infection, while under MMF therapy, without subsequent PTLD. Three patients had CMV primary infection, and five CMV reactivation, under MMF therapy. Seven remained asymptomatic, and one presented with CMV enteritis. CONCLUSIONS: These preliminary results suggest that MMF is an effective and safe immunosuppressant in pediatric LT recipients. Its use is hampered by frequent gastrointestinal and hematological side-effects. MMF does not seem to increase the risk of PTLD nor CMV disease.

Burkitt Lymphoma↗
PubMed2001

Simplified technique of orthotopic liver transplantation in pigs.

BACKGROUND: Pig models have become common in transplantation immunological research. However, in pigs, clamping of the venous splanchnic system during orthotopic liver transplantation (OLT) is responsible for high morbidity and mortality rates; therefore, the use of venovenous bypass (VVB) is advocated. Because venous bypass can also cause specific complications, a simplified method for OLT in pigs has been developed and evaluated in terms of morbidity and mortality. METHODS: Twenty-three OLTs were performed between pairs of inbred miniature swine. Donor and recipient pairs (weighing 20-35 kg) were selected at 3-6 months of age. In the donor, the portal vein, infrahepatic vena cava, and suprahepatic vena cava were dissected, whereas the hepatic artery was preserved in continuity with the coeliac trunk and the abdominal aorta up to the iliac bifurcation. In situ cold perfusion was then performed. The recipient was prepared simultaneously by another surgical team. After total hepatectomy and complete portal and caval clamping, the suprahepatic vena cava and portal vein were sutured; VVB was not used. After completion of both venous sutures, the liver graft was reperfused. The infrahepatic vena cava was then anastomosed and unclamped. The donor aorta conduit was implanted end-to-side to the recipient infrarenal aorta, and the biliary reconstruction consisted of a cholecystojejunostomy with a Roux-Y loop. RESULTS: Twenty of 23 (87%) animals survived more than 1 week (7-483 days). The mean anhepatic time was 29.6+/-4.12 min. Although severe hypotension was noted during the anhepatic phase, the hemodynamic status rapidly recovered and stabilized after graft reperfusion. CONCLUSION: Simplified technique without VVB is appropriate for successfully achieving OLT in pigs.

Animals↗
PubMed2001

Hepatic vein obstruction due to hypertrophy of right split-liver adult allograft.

The increasing shortage of liver allografts has led to the development of split liver transplantation. More frequent applications have permitted the resolution of most of its technical complications. A hitherto unreported complication of split liver transplantation, hepatic vein obstruction caused by hypertrophy of a right split-liver adult allograft, is discussed. As surgical correction was impossible, the outflow obstruction was treated successfully with interventional radiology.

Adult↗
PubMed2001

Favorable outcome of orthotopic liver transplantation in a patient with subacute liver failure due to the emergence of a hepatitis B YMDD escape mutant virus.

BACKGROUND/AIMS: Patients with end-stage liver disease due to chronic hepatitis B infection in whom a YMDD escape hepatitis B virus (HBV) mutant has emerged under lamivudine treatment are generally denied liver transplantation (OLT). METHODS: We report the case of a male patient who was started on prophylactic treatment with lamivudine in the context of recurrent episodes of HBV reactivation during high dose immunosuppressive therapy for relapsing severe pulmonary sarcoidosis. RESULTS: Following the emergence of a YMDD escape mutant virus under lamivudine treatment, he developed subacute liver failure requiring liver transplantation. The patient was treated with a combination of intravenous hepatitis B immune globulin (HBIG) which was started perioperatively and also continued lamivudine after OLT. Twelve months after OLT, there was no evidence of HBV reinfection of the liver graft with the use of HBIG and lamivudine. CONCLUSIONS: This observation suggests that emergence of the YMDD mutation is not a contra-indication to OLT, providing adequate immunoprophylaxis using HBIG and lamivudine combination therapy.

Adult↗
PubMed2000

A 12-day course of FK506 allows long-term acceptance of semi-identical liver allograft in inbred miniature swine.

BACKGROUND: Spontaneous tolerance to liver allograft has been reported previously in outbred pig models, but the lack of genetic background did not allow to analyze the impact of the major histocompatibility complex (MHC) on tolerance induction. A model of semi-identical liver allograft was therefore developed in inbred miniature swine in order to mimic the clinical situation of living related liver transplant (parent into infant) and to study a protocol for inducing tolerance to liver allograft. METHODS: SLAdd (class Id/d, class IId/d) pigs received orthotopic liver allograft from heterozygous SLAcd (class Ic/d, class IIc/d) miniature swine. Eight animals did not receive immunosuppression. Fourteen SLAdd animals had a 12-day course of FK506 and were divided in two subgroups. In subgroup FK-1, six pigs received a daily intramuscular injection of FK506 at 0.1-0.4 mg/kg, in order to reach daily trough levels between 7 and 20 ng/ml; in subgroup FK-2, eight additional animals received two daily injections of FK506 at 0.05 mg/kg regardless of the daily trough levels. Graft survival, liver biological tests, histology, cellular and humoral immune responses, as well as detection of microchimerism were assessed in all groups. RESULTS: All untreated animals rejected their allograft and died within 28.1 +/- 9.5 days. These rejector animals developed a significant anti-donor cellular and humoral immune response. No peripheral or lymphoid tissue microchimerism was detected in this group. In contrast, long-term survival was obtained in five FK-treated animals (112, 154, 406, 413, and 440 days), whereas several pigs died with a normal allograft function from either overimmunosuppression or intercurrent causes. All FK-treated pigs developed a specific anti-donor unresponsiveness in both cell mediated lymphocytotoxicity and mixed lymphocyte reaction and did not develop anti-donor alloantibodies. The study of the anti-donor immune response by mixed lymphocyte reaction, during the first postoperative week, demonstrated a specific anti-donor unresponsiveness in the peripheral blood from the first posttransplant day. Although microchimerism was detectable in the peripheral blood for several postoperative weeks (maximum 10 weeks) in FK-treated animals, donor cells or DNA were not detected during the long-term follow-up in peripheral blood or lymphoid tissues. CONCLUSIONS: Spontaneous tolerance to semi-identical orthotopic liver allograft did not occur, whereas a 12-day course of FK506 allowed long-term graft acceptance. All FK-treated animals developed in vitro signs of specific immune unresponsiveness and transient peripheral microchimerism. The specific anti-donor cellular unresponsiveness occurred on the first postoperative day after surgery and was of long-term duration. The study of the early immunological events in this model could be of major importance regarding clinical living related liver transplantation.

Animals↗
PubMed2000

Adult liver transplantation: the Université Catholique de Louvain experience.

Liver transplantation remains a formidable surgical and medical procedure. The larger single centre experience confirms that standardization of perioperative care and simplification of the surgical procedure markedly improve results. Further efforts must be made in relation to immunosuppressive therapy in order to minimize late morbidity and mortality.

Adolescent↗
PubMed1999

Preserved vascular homograft for revascularization of pediatric liver transplant: a clinical, histological, and bacteriological study.

BACKGROUND: Arterial or venous homografts are frequently implanted for vascular reconstruction in orthotopic liver transplantation (OLT). When fresh vascular homografts (VH) from the same donor were not available, VH from another donor preserved at 4 degrees C in Terasaki (Ter) solution (modified lymphocyte culture medium) were used. METHODS: The clinical results after implantation of Ter-stored VH versus fresh VH in the revascularization of pediatric OLT were studied retrospectively. Short- and long-term follow-up of vascular patency was carried out by doppler ultrasonography in each case. A histological and bacteriological study of nonimplanted VH stored at 4 degrees C in saline (Sal), Ter and University of Wisconsin (UW) solutions for various time periods (days 0-28) was also undertaken. RESULTS: Between 1989 and 1996, 21 iliac arteries and 21 iliac veins preserved in Ter solution (mean preservation time: 8 days; range 1-26) and 100 fresh VH (68 arteries and 32 veins) (preservation time: 8 hr, range 4-21) were used in pediatric OLT. Thrombosis rates were 0 of 21 for stored arteries vs. 7 of 68 (10%) for fresh arteries (NS) and 3 of 21 (14%) for stored veins vs. 3 of 32 (9%) for fresh veins (NS). Actuarial graft survival rates were similar in both groups. Histological analysis of stored, nonimplanted VH invariably showed endothelial destruction within 24-48 hr after procurement. The bacteriological study showed contamination rates of 14 of 25 (56%) for Sal-stored VH, 5 of 25 (20%) for UW, and 1 of 19 (5%) for Ter (Sal vs. UW and Sal vs. Ter: P<0.01; UW vs. Ter: NS). CONCLUSIONS: Ter-preserved cadaveric VH could be safely used in OLT despite early destruction of endothelium.

Adenosine↗
PubMed1999

European collaborative study on factors influencing outcome after liver transplantation for hepatitis C. European Concerted Action on Viral Hepatitis (EUROHEP) Group.

BACKGROUND & AIMS: Liver transplantation for hepatitis C virus (HCV)-related liver disease is characterized by frequent graft infection by HCV. The prognosis and risk factors for morbidity and mortality in this condition were determined. METHODS: A retrospective study of 652 consecutive anti-HCV-positive patients undergoing liver transplantation between 1984 and 1995 in 15 European centers was conducted; 102 patients coinfected with hepatitis B virus (HBV) received immunoglobulin prophylaxis for antibody to hepatitis B surface antigen. RESULTS: Overall, 5-year survival was 72%. Five-year actuarial rates of hepatitis and cirrhosis were 80% and 10%. Genotypes 1b, 1a, and 2 were detected in 214 (80%), 24 (9%), and 24 (9%) of 268 patients analyzed. The only discriminant factor for patient or graft survival was hepatocellular carcinoma as primary indication. Independent risk factors for recurrent hepatitis included the absence of HBV coinfection before transplantation (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2-2.6; P = 0.005), genotype 1b (RR, 2; 95% CI, 1.3-2.9; P = 0.01), and age > 49 years (RR, 1.4; 95% CI, 1.1-1.8; P = 0.01). CONCLUSIONS: The results of transplantation for HCV-related disease are compromised by a significant risk of cirrhosis, although 5-year survival is satisfactory. Genotype 1b, age, and absence of pretransplantation coinfection by HBV are risk factors for recurrent HCV.

Female↗
PubMed1999

Living-related liver transplantation: is Doppler sonography sufficient to define the hepatic artery anatomy before surgery?

OBJECTIVE: to evaluate the accuracy of colour Doppler sonography (CDS) in the assessment of the left hepatic arterial supply in living donors before hepatic transplantation. MATERIAL AND METHODS: Pre-operative sonographic Doppler data of the left hepatic artery (LHA) were compared retrospectively with the selective hepatic angiographic data and the intra-operative observations in 60 living donors. RESULTS: Pre-operative Doppler data of the LHA were available in 53 cases and incomplete or absent in seven cases. In 51 cases (96%) the origin of the LHA or an accessory LHA were correctly described at Doppler sonography (44 classical LHA in anatomic position, seven accessory LHA). In 11 cases (21%), Doppler data were insufficient or incorrect to define the arterial supply of the hepatic segments II, III and IV. Doppler studies were unable to determine the length or the diameter of the LHA. CONCLUSION: Doppler sonography seems to be able to define the main left hepatic artery anatomy. Selective hepatic angiography is still indicated to determine the length, diameter and intra-hepatic segmental supply.

Hepatic Artery↗
PubMed1998

Pediatric liver transplantation: from the full-size liver graft to reduced, split, and living related liver transplantation.

Between 1984 and 1996, the authors performed 499 liver transplants in 416 children less than 15 years old. The overall patient survival at 10 years was 76.5%. It was 71.3% for the 209 children grafted in 1984-1990; 78.5% for biliary atresia (n = 286), 87.3% for metabolic diseases (n = 59), and 72.7% for acute liver failure (n = 22). The 5-year survival was 73.6% for the 209 children grafted in 1984-1990 and 85% for the 206 grafted in 1991-1996. Scarcity of size-matched donors led to the development of innovative techniques: 174 children who electively received a reduced liver as a first graft in our center had a 5-year survival of 76% while 168 who received a full-size graft had a survival of 85% (NS). Results of the European Split Liver Registry showed 6-month graft survival similar to results obtained with full-size grafts collected by the European Liver Transplant Registry. Extensive use of these techniques allowed the mortality while waiting to be reduced from 16.5% in 1984-1990 to 10% in 1991-1992. It rose again to 17% in 1993, leading the authors to develop a program of living related liver transplantation (LRLT). The legal and ethical aspects are analyzed. Between July 1993 and October 1997, the authors performed 53 LRLTs with 90% survival. In elective cases, a detailed analysis was made of the 45 children listed for LRLT between July 1993 and March 1997 and the 79 registered on the cadaveric waiting list during the same period. Mortality while waiting was 2% and 14.5% for the LRLT and cadaveric lists, respectively. The retransplantation rate was 4.6% and 16.1% for LRLT and cadaveric transplants, respectively. Overall post-transplant survival was 88% and 82% for children who received a LRLT or a cadaveric graft, respectively. Overall survival from the date of registration was 86% and 70% (P < 0.05) for LRLT or cadaveric LT respectively. The 2-year post-transplant survival in children less than 1 year of age at transplantation was 88.8% and 80. 3% with a LRLT or cadaveric graft, respectively; patient survival after 3 months post-transplant was 95.8% and 91.9% for stable children waiting at home, 93.7% and 93.7% in children hospitalized for complications of their disease, and 89.5% and 77.7% for children hospitalized in an intensive care unit at the time of transplantation for children who received a LRLT or cadaveric graft, respectively. It is concluded that LRLT seems to be justified for multidisciplinary teams having a large experience with reduced and split liver grafting.

Child↗
PubMed1998

The effects of intraoperative intravenous clonidine on fluid requirements, hemodynamic variables, and support during liver transplantation: a prospective, randomized study.

UNLABELLED: In this prospective, nonblind study, we report the use of clonidine during orthotopic liver transplantation (OLT). Twenty adult patients in a stable medical condition were studied. General anesthesia consisted of isoflurane in air/oxygen and sufentanil. Patients in the clonidine group received a slow i.v. infusion (15 min) of 4 microg/kg clonidine during induction. The other patients were used as controls. I.v. fluid requirements were determined as follows: albumin (4% solution) was administered to maintain filling pressures to a pulmonary capillary wedge pressure (PCWP) of more than 12 mm Hg. Packed red blood cells were transfused to maintain a hemoglobin level of 8-9 g/dL. Circulatory stability was evaluated using: systolic and diastolic arterial blood pressure and heart rate recorded at 2-min intervals; and the vasopressor/inotropic support required to maintain adequate hemodynamic variables after reperfusion. Intraoperative albumin and packed red blood cell requirements were significantly reduced in patients in the clonidine group (1644 +/- 140 and 50 +/- 50 mL vs 2867 +/- 226 mL and 1350 +/- 443 mL; P < 0.05). Heart rate was significantly slower in patients of the clonidine group. There were no differences in systolic arterial blood pressure. After reperfusion, patients in the control group showed significantly lower diastolic arterial blood pressure, required more vasopressor/inotropic support, and were more acidotic than patients in the clonidine group. We conclude that the administration of 4 microg/kg clonidine during induction of OLT significantly reduced the intraoperative requirements of i.v. fluids and blood products without compromising circulatory stability. Improvement in immediate reperfusion-induced disturbances was observed. IMPLICATIONS: The administration of 4 microg/kg clonidine during induction of liver transplantation significantly reduced the intraoperative requirements for i.v. fluids and blood products without compromising the circulatory stability. Improvement in immediate reperfusion-induced disturbances was also observed.

Blood Volume↗