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Olivier Boillot

Publications and source records attributed to Olivier Boillot.

At least 19 recordsLinked to original sources
PubMed2025

Donor HLA Class I Evolutionary Divergence and Late Allograft Rejection After Liver Transplantation in Children: An Emulated Target Trial.

HLA evolutionary divergence (HED), a continuous metric quantifying the differences between each amino acid of two homologous HLA alleles, reflects the importance of the immunopeptidome presented to T lymphocytes. It has been associated with rejection after liver transplantation. This retrospective cohort study aimed to analyse the potential effect of donor or recipient HED on liver transplant rejection in a new series of patients transplanted during childhood and followed in adulthood. The study included 120 children who had been transplanted between 1991 and 2010 and were followed by routine biopsies and histological evaluations with a median of 14.1 years post-LT. Liver biopsies were performed routinely 1, 5, 10 and 20 years after transplantation and in the event of liver dysfunction. HED was calculated using the physicochemical Grantham distance for donor and recipient Class I (HLA-A, -B, -C) and Class II (HLA-DRB1, -DQB1) alleles. The influence of HED on rejection was analysed using inverse probability weighting (IPW) and target trial emulation using the g method. Based on the IPW score, donor HED class I was correlated with the occurrence of late (> 90 days) rejection (HR, 1.19, 95% CI: 1.01-1.40) independently of HLA mismatches, donor age and initial induction. The emulated target trial confirmed that donor HED Class I has a causal effect on liver graft rejection and this relationship was observed long-term.

Humans↗
PubMed2006

Role of immunosuppression and tumor differentiation in predicting recurrence after liver transplantation for hepatocellular carcinoma: a multicenter study of 412 patients.

AIM: To assess pre-orthotopic liver transplantation (OLT) factors that could be evaluated pre-operatively or controlled post-operatively associated with hepatocellular carcinoma (HCC) recurrence and disease-free survival after liver transplantation (LT). METHODS: Four hundred and twelve patients transplanted for HCC between 1988 and 1998 in 14 French centers, who survived the postoperative period were studied. Kaplan Meier estimates were calculated for 24 variables potentially associated with recurrence of HCC. Uni- and multivariate analyses were conducted to identify independent predictors of recurrence. RESULTS: Overall 5-year disease-free survival was 57.1%. By univariate analysis, variables associated with disease-free survival were: presence of cirrhosis (P = 0.001), etiology of liver disease (P = 0.03), alpha fetoprotein level (< 200, 200 to 2000, or > 2000; P < 0.0001), gamma-GT activity (N, N to 2N or > 2N; P = 0.02), the number of nodules (1, 2-3 or > or = 4; P = 0.02), maximal diameter of the largest nodule (< 3 cm, 3 to 5 cm or > 5 cm; P < 0.0001), the sum of the diameter of the nodules (< 3 cm, 3 to 5 cm, 5 to 10 cm or > 10 cm; P < 0.0001), bi-lobar location (P = 0.01), preoperative portal thrombosis (P < 0.0001), peri-operative treatment of the tumor (P = 0.002) and chemoembolization (P = 0.03), tumor differentiation (P = 0.01), initial type of calcineurin inhibitor (P = 0.003), the use of antilymphocyte antibodies (P = 0.02), rejection episodes (P = 0.003) and period of LT (P < 0.0001). By multivariate analysis, 6 variables were independently associated with HCC recurrence: maximal diameter of the largest nodule (P < 0.0001), time of LT (P < 0.0001), tumor differentiation (P < 0.0001), use of anti-lymphocyte antibody (ATG) or anti-CD3 antibody (OKT3) (P = 0.005), preoperative portal thrombosis (P = 0.06) and the number of nodules (P = 0.06). CONCLUSION: This study identifies immunosuppression, through the use of ATG or OKT3, as a predictive factor of tumor recurrence, and confirms the prognostic value of tumor differentiation.

Analysis of Variance↗
PubMed2006

Evaluation of IGL-1 preservation solution using an orthotopic liver transplantation model.

AIM: To compare, in a pig liver transplantation model, the protective effect of UW with that of IGL-1, a high-sodium preservation solution containing polyethylene glycol (PEG) as an oncotic supply. METHODS: All livers were harvested and grafted orthotopically according to standard techniques. The livers were washed out and preserved for 7 h in IGL-1 (n = 6) or in UW solution (n = 7) at 4 degree centigrade. In a sham group (n = 4), the livers underwent a 60-min warm ischemia at 37 degree centigrade. The hepatocellular injury was assessed in organ preservation solution washed out from the graft at the end of ischemic storage (before revascularization), and in serum 2 h after reperfusion and daily for up to 6 d. RESULTS: Livers preserved in IGL-1 solution released markedly less AST than that preserved in the UW solution before and after revascularization (P < 0.05). Besides, the activity of creatine kinase-BB, a marker of sinusoidal lining cells injury, was higher in the UW group than in the IGL-1 group (P < 0.05). Histological results showed less necrotic regions in livers preserved in IGL-1 solution; however, no difference was observed for inflammation. CONCLUSION: IGL-1 liquid effectively protects parenchymal and non-parenchymal cells against preservation-reperfusion injuries.

Animals↗
PubMed2006

Conversion from tacrolimus to cyclosporine in liver transplanted patients with diabetes mellitus.

Adverse effects associated with calcineurin inhibitors may impact their clinical utility in some patients. This study characterizes the clinical outcomes of liver transplanted (LT) patients who experienced diabetes mellitus (DM) on tacrolimus-based regimen and were converted to cyclosporine-based therapy. Since January 2002, all patients with DM on a tacrolimus-based regimen were recruited and converted to cyclosporine-based therapy, after a 6-month minimal follow-up after LT. Clinical and laboratory data related to the clinical course of the patients were recorded. Twenty-five patients were included after a median delay of 54 months after LT [seven women and 18 men, 51 years (range 30-69)]. There were 11 patients with insulin-treated DM (ITDM), 14 patients with noninsulin-treated DM (NITDM), and the glycemic control was poor (HbA1c > 6.5%) in 13/25 patients (52%). After a median follow-up of 20 months after conversion, there were four patients with ITDM, 17 patients with NITDM, and four patients without DM, and the glycemic control was poor in 3/25 patients (12%). Four patients returned to tacrolimus because of arterial hypertension or digestive side-effects. In conclusion, our results suggest that conversion from tacrolimus to cyclosporine in stable LT patients with DM is well tolerated and beneficial on glycemic control.

Adult↗
PubMed2006

Living donor liver transplantation in high-risk vs. low-risk patients: optimization using statistical models.

Living donors represent a recognized alternative for facilitating the access to transplantation in a period of organ shortage. However, which candidates should be preferentially considered for living-donor liver transplantation (LDLT) is debated. The aim of this study was to create statistical models to determine which strategies of selection for LDLT provide the most efficient contribution. The study included 331 patients listed for deceased-donor transplantation (DDLT) and 128 transplanted with living donors. Statistical models predicting the events following listing were created and combined in a multistate model allowing the testing of different strategies of selection for LDLT and to compare their results. Taking 3-yr survival after listing as the principal end-point, selecting the 20% patients at highest risk of death on the waiting list gave better results than selecting the 20% patients at lowest risk of death after LDLT (70% vs. 64%, respectively). These strategies resulted in waiting list mortality rates of 17% and 8%, respectively. One-year survival after LDLT was lower in high-risk patients (85%) than in low-risk patients (91%). However, the 1-yr survival benefit derived from LDLT was 75% in high-risk patients while it was nil in low-risk patients. In conclusion, LDLT is more effective for overcoming the consequences of organ shortage when performed in patients at high risk of death on the waiting list. On an individual basis, the sickest patients are those who derive the most important benefit from LDLT. This study provides incentives for considering LDLT in high-risk patients.

Adolescent↗
PubMed2006

Preservation of steatotic livers in IGL-1 solution.

A new Institut Georges Lopez (IGL-1) solution was used to preserve steatotic livers. Steatotic (obese [Ob]) and nonsteatotic (lean [Ln]) livers from Zücker rats (n = 16, 8 Ln and 8 Ob) were preserved for 24 hours at 4 degrees C in University of Wisconsin (UW) or IGL-1 solution, respectively, and then perfused ex vivo for 2 hours at 37 degrees C. Additionally, Ob and Ln livers (n = 16, 8 Ln and 8 Ob) were preserved in IGL-1 plus Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME). Hepatic injury and function (aminotransferases, bile production, bromosulfophthalein clearance), and factors potentially involved in the susceptibility of steatotic livers to ischemia-reperfusion injury, such as oxidative stress, mitochondrial damage, and vascular resistance, were studied. Nitric oxide (NO) production and constitutive and inducible NO synthase were also measured. Steatotic and nonsteatotic livers preserved in IGL-1 solution showed lower transaminases, malondialdehyde, glutamate dehydrogenase levels, and higher bile production than UW-solution-preserved livers. IGL-1 solution protected against oxidative stress, mitochondrial damage and the alterations in vascular resistance associated with cold ischemia-reperfusion. Thus, at the end of reperfusion period, aspartate aminotransferase levels in steatotic livers were 281 +/- 6 U/L in UW vs. 202 +/- 10 U/L in IGL-1 solution. Glutamate dehydrogenase was 463 +/- 75 U/L in UW vs. 111 +/- 4 U/L in IGL-1 solution, and oxidative stress was 3.0 +/- 0.1 nmol/mg prot in UW vs. 2.0 +/- 0.1 nmol/mg prot in IGL-1 solution. These beneficial effects of IGL-1 solution were abolished by the addition of L-NAME, which implicates NO in the benefits of IGL-1. In conclusion, IGL-1 solution provided steatotic livers with better protection against the deleterious effects of cold ischemia-reperfusion injury than did UW solution.

Alanine Transaminase↗
PubMed2006

Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in liver transplant patients presenting gastrointestinal disorders: a pilot study.

Gastrointestinal (GI) disorders are one of the main adverse events in patients treated by mycophenolic acid (MPA). The aim of this prospective study was to evaluate the effect of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in liver transplant patients presenting GI side-effects Since January 2003, stable liver transplant patients receiving MMF and presenting GI disorders, without evidence of other origin than MMF were enrolled. Conversion was performed without a washout period at an equimolar daily dosage. Thirty-six patients were included after a median delay of 45 months after liver transplantation (LT) (16 women and 20 men, median age of 47 years). Diarrhoea was the main clinical symptom (n = 28, 77.7%). At the time of inclusion, patients were treated with MMF since 18 months (range 3-28) and GI disorders were known for 9 months (range 3-12). After a median follow-up of 12 months after conversion, GI disorders were resolved in 20 patients (55%), improved in 6 patients (17%) and not modified or worsened in 10 patients (28%). Our results strongly suggest that conversion from MMF to EC-MPS in liver transplant patients can improve gastrointestinal disorders in a majority of the patients, and therefore might be considered as the best therapeutic option.

Adolescent↗
PubMed2006

Impact of UCSF criteria according to pre- and post-OLT tumor features: analysis of 479 patients listed for HCC with a short waiting time.

Orthotopic liver transplantation (OLT) indication for hepatocellular carcinoma (HCC) is currently based on the Milan criteria. The University of California, San Francisco (UCSF) recently proposed an expansion of the selection criteria according to tumors characteristics on the explanted liver. This study: 1) assessed the validity of these criteria in an independent large series and 2) tested for the usefulness of these criteria when applied to pre-OLT tumor evaluation. Between 1985 and 1998, 479 patients were listed for liver transplantation (LT) for HCC and 467 were transplanted. According to pre-OLT (imaging at date of listing) or post-OLT (explanted liver) tumor characteristics, patients were retrospectively classified according to both the Milan and UCSF criteria. The 5-yr survival statistics were assessed by the Kaplan-Meier method and compared by the log-rank test. Pre-OLT UCSF criteria were analyzed according to an intention-to-treat principle. Based on the pre-OLT evaluation, 279 patients were Milan+, 44 patients were UCSF+ but Milan- (subgroup of patients that might benefit from the expansion), and 145 patients were UCSF- and Milan-. With a short median waiting time of 4 months, 5-yr survival was 60.1 +/- 3.0%, 45.6 +/- 7.8%, and 34.7 +/- 4.0%, respectively (P < 0.001). The 5-yr survival was arithmetically lower in UCSF+ Milan- patients compared to Milan+ but this difference was not significant (P = 0.10). Based on pathological features of the explanted liver, 5-yr survival was 70.4 +/- 3.4%, 63.6 +/- 7.8%, and 34.1 +/- 3.1%, in Milan+ patients (n = 184), UCSF+ Milan- patients (n = 39), and UCSF- Milan- patients (n = 238), respectively (P < 0.001). However, the 5-yr survival did not differ between Milan+ and UCSF+ Milan- patients (P = 0.33). In conclusion, these results show that when applied to pre-OLT evaluation, the UCSF criteria are associated with a 5-yr survival below 50%. Their applicability is therefore limited, despite similar survival rates compared to the Milan criteria, when the explanted liver is taken into account.

California↗
PubMed2006

Impact of adult-to-adult living donor liver transplantation on access to transplantation and patients' survival: an 8-year single-center experience.

While the number of candidates for liver transplantation has increased in the recent years, the pool of cadaveric donor organs has remained constant and the waiting time progressively increases. These facts led us to start a program of adult-to-adult living-donor liver transplantation in 1998. The aim of this study was to compare the outcome of all patients put on the waiting list since 1998. Between January 1, 1998, and January 1, 2005, 505 patients were put on the waiting list in our center, and living donor liver transplantation was considered in 57 cases (11.3%). At the time of evaluation (April 1, 2006), liver transplantation was performed in 377 patients (46 living donor liver transplantations), and 89 patients died on waiting list. On an intention-to-treat basis, the 1-year survival rate from the time of listing was 87.5% in the "living donor" group vs. 76.2% in the "cadaveric donor" group (P < 0.05), whereas the 1-year survival after liver transplantation was similar (92.3% vs. 86.9%). Our living donor liver transplantation program was able to improve the access to liver transplantation by reducing waiting time and the number of deaths on waiting list, despite the fact that these patients were more critically ill (liver failure and/or liver cancer).

Adolescent↗
PubMed2006

Liver transplantation for hereditary hemorrhagic telangiectasia: Report of the European liver transplant registry.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is a rare disease characterized by the presence of arteriovenous malformations. Hepatic involvement can lead to life-threatening conditions. MATERIAL AND METHODS: Forty patients, reported to the European Liver Transplant Registry, were analyzed to define the role of liver transplantation in the treatment of the hepatic disease form. Indications for transplantation were classified according to Garcia-Tsao: cardiac failure (14 patients), biliary necrosis causing hepatic failure (12 patients), severe portal hypertension (5 patients), cardiac failure and biliary necrosis (6 patients), cardiac failure and portal hypertension (2 patients), and cardiac failure associated with biliary necrosis and portal hypertension (1 patient). Eighteen (81%) of 22 patients had pulmonary artery hypertension. Twelve (30%) patients had pretransplant hepatic interventions. Follow-up was complete for all patients with a mean of 69 months (range, 0-230 months). RESULTS: One-, 5- and 10-year actuarial patient and graft survival rates are 82.5%. Six of the 7 pretransplant procedures performed on the hepatic artery were severely complicated. Cardiovascular function documented in 24 patients improved in 18 patients and remained stable in 5 patients; 1 patient died perioperatively of acute heart failure. Twenty-four (60%) patients had post-transplant complications, all but one occurring within the first 4 posttransplant months. Seven (17.5%) patients died perioperatively, 6 of them due to bleeding and 1 due to cardiac failure; 1 (2.5%) patient died late due to chronic rejection. There were 2 possible recurrences. Quality of life markedly improved in all 32 surviving patients. CONCLUSION: The results of the largest reported transplant series in the treatment of hepatic-based HHT are excellent. Elimination of hepatobiliary sepsis and reversal of cardiopulmonary changes dramatically improve quality of life of the recipients. LT should be proposed earlier in the course of symptomatic hepatic HHT presenting with life-threatening conditions. Palliative interventions, especially on the hepatic artery, should be avoided in view of their high (infectious) complication rate.

Adult↗
PubMed2005

The outcome of 400 consecutive liver grafts using the aortic perfusion-only technique.

The goal of this study is to establish the effect of cadaveric liver retrieval, using the technique of aortic perfusion only, on liver graft function, and to identify associated potential risk factors for graft dysfunction. The authors reviewed the outcome of 400 consecutive, orthotopic, cadaveric liver transplantation retrieved by the technique of aortic perfusion only. Relevant parameters pertaining to the donor, recipient, procurement, graft and peri-operative variables are analyzed to assess their influence on graft function. The univariant analysis revealed that donor age, body mass index, blood pressure, and vasopressor dependence influence graft function. Furthermore, predictors of dysfunction included prolonged anhepatic phase, transplantation duration and partial grafts. In addition, multivariant analysis revealed significant association between obesity of donors, partial graft, and dysfunction. The technique of aortic perfusion only, is a simple and reproducible procedure. The post-transplantation outcomes appear to be similar to those reported for the traditional liver procurement technique.

Adult↗
PubMed2005

Corticosteroid-free immunosuppression with tacrolimus following induction with daclizumab: a large randomized clinical study.

This open, randomized (1 : 1), multicenter, 3-month study compared a dual tacrolimus plus steroids (Tac / steroids) regimen with a steroid-free immunosuppressive regimen of tacrolimus following daclizumab induction therapy (Tac / Dac) in adult liver transplant recipients. The full analysis set comprised 347 patients in the Tac / steroids group and 351 in the Tac / Dac group. Mean tacrolimus dose during month 3 was 0.11 mg/kg/day in both groups; mean whole-blood trough levels during month 3 were 10.9 ng/mL (Tac / steroids) and 10.6 ng/mL (Tac / Dac). The incidence of biopsy-confirmed acute rejection that required treatment was similar in both groups: 26.5% in the Tac / steroids group and 25.4% in the Tac / Dac group (P = .727). However, the incidence of biopsy-confirmed corticosteroid-resistant acute rejection was higher in the Tac / steroids group than in the Tac / Dac group (6.3 vs. 2.8%; P = .027). Kaplan-Meier estimates of graft survival (92.2 vs. 90.5%) and patient survival (94.5 vs. 93.7%) were similar in both groups. While also the overall adverse event profiles were similar, the incidences of diabetes mellitus (15.3 vs. 5.7%, respectively; P < .001) and cytomegalovirus infection (11.5 vs. 5.1%, respectively; P = .002) were higher in the Tac / steroids group compared with the Tac / Dac group. Mean cholesterol levels increased by 16% in the Tac / steroids group, but were unchanged in the Tac / Dac group during the study. In conclusion, tacrolimus monotherapy following daclizumab induction is an effective and safe regimen, with an advantage over concomitant steroid-maintenance therapy in terms of a lower incidence of diabetes and viral infection, and a lower incidence of steroid-resistant acute rejection.

Acute Disease↗
PubMed2005

Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma.

The actual impact of transarterial chemoembolization before liver transplantation (LT) for hepatocellular carcinoma (HCC) on patient survival and HCC recurrence is not known. Between 1985 and 1998, 479 patients with HCC in 14 French centers were evaluated for LT. Among these 479 patients, this case-control study included 100 patients who received transarterial chemoembolization before LT (TACE group) and 100 control patients who did not receive chemoembolization (no-TACE group). Patients and controls were matched for the pre-LT tumor characteristics, the period of transplantation, the time spent on the waiting list, and pre- and posttransplantation treatments. Kaplan-Meier estimates were calculated 5 years after LT and were compared with the log-rank test. The mean waiting time before LT was 4.2 +/- 3.2 months in the TACE group and 4.3 +/- 4.4 months in the no-TACE group. The median number of TACE procedures was 1 (range: 1-12). Demographic data, median alpha-fetoprotein level (21.6 ng/mL and 22.0 ng/mL, respectively), and pre- and post-LT morphologic characteristics of the tumors did not differ in the TACE and no-TACE groups. Overall 5-year survival was 59.4% with TACE and 59.3% without TACE (ns). Survival rates did not differ significantly between the two groups with respect to the time on the waiting list, the tumor diameter, or the type of TACE (selective or nonselective). In the TACE group, 30 patients had tumor necrosis > or =80% on the liver explant with a 5-year survival rate of 63.2%, compared with 54.2% among their matched controls (P = 0.9). In conclusion, with a mean waiting period of 4.2 months and 1 TACE procedure, pre-LT TACE does not influence post-LT overall survival and disease-free survival.

Carcinoma, Hepatocellular↗