Efficacy and Safety of Everolimus and Mycophenolic Acid With Early Tacrolimus Withdrawal After Liver Transplantation: A Multicenter Randomized Trial.

SIMCER was a 6-mo, multicenter, open-label trial. Selected de novo liver transplant recipients were randomized (week 4) to everolimus with low-exposure tacrolimus discontinued by month 4 (n = 93) or to tacrolimus-based therapy (n = 95), both with basiliximab induction and enteric-coated mycophenolate sodium with or without steroids. The primary end point, change in estimated GFR (eGFR; MDRD formula) from randomization to week 24 after transplant, was superior with everolimus (mean eGFR change +1.1 vs. -13.3 mL/min per 1.73 m2 for everolimus vs. tacrolimus, respectively; difference 14.3 [95% confidence interval 7.3-21.3]; p < 0.001). Mean eGFR at week 24 was 95.8 versus 76.0 mL/min per 1.73 m2 for everolimus versus tacrolimus (p < 0.001). Treatment failure (treated biopsy-proven acute rejection [BPAR; rejection activity index score >3], graft loss, or death) from randomization to week 24 was similar (everolimus 10.0%, tacrolimus 4.3%; p = 0.134). BPAR was more frequent between randomization and month 6 with everolimus (10.0% vs. 2.2%; p = 0.026); the rate of treated BPAR was 8.9% versus 2.2% (p = 0.055). Sixteen everolimus-treated patients (17.8%) and three tacrolimus-treated patients (3.2%) discontinued the study drug because of adverse events. In conclusion, early introduction of everolimus at an adequate exposure level with gradual calcineurin inhibitor (CNI) withdrawal after liver transplantation, supported by induction therapy and mycophenolic acid, is associated with a significant renal benefit versus CNI-based immunosuppression but more frequent BPAR.

Ad Integrum Functional and Volumetric Recovery in Right Lobe Living Donors: Is It Really Complete 1 Year After Donor Hepatectomy?

The partial liver's ability to regenerate both as a graft and remnant justifies right lobe (RL) living donor liver transplantation. We studied (using biochemical and radiological parameters) the rate, extent of, and predictors of functional and volumetric recovery of the remnant left liver (RLL) during the first year in 91 consecutive RL donors. Recovery of normal liver function (prothrombin time [PT] ≥70% of normal and total bilirubin [TB] ≤20 µmol/L), liver volumetric recovery, and percentage RLL growth were analyzed. Normal liver function was regained by postoperative day's 7, 30, and 365 in 52%, 86%, and 96% donors, respectively. Similarly, mean liver volumetric recovery was 64%, 71%, and 85%; whereas the percentage liver growth was 85%, 105%, and 146%, respectively. Preoperative PT value (p = 0.01), RLL/total liver volume (TLV) ratio (p = 0.03), middle hepatic vein harvesting (p = 0.02), and postoperative peak TB (p < 0.01) were predictors of early functional recovery, whereas donor age (p = 0.03), RLL/TLV ratio (p = 0.004), and TLV/ body weight ratio (p = 0.02) predicted early volumetric recuperation. One-year post-RL donor hepatectomy, though functional recovery occurs in almost all (96%), donors had incomplete restoration (85%) of preoperative total liver volume. Modifiable predictors of regeneration could help in better and safer donor selection, while continuing to ensure successful recipient outcomes.

Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a syndrome that occurs in cirrhosis characterized by organ failure(s) and high mortality rate. There are no biomarkers of ACLF. The LCN2 gene and its product, neutrophil gelatinase-associated lipocalin (NGAL), are upregulated in experimental models of liver injury and cultured hepatocytes as a result of injury by toxins or proinflammatory cytokines, particularly Interleukin-6. The aim of this study was to investigate whether NGAL could be a biomarker of ACLF and whether LCN2 gene may be upregulated in the liver in ACLF. METHODS: We analyzed urine and plasma NGAL levels in 716 patients hospitalized for complications of cirrhosis, 148 with ACLF. LCN2 expression was assessed in liver biopsies from 29 additional patients with decompensated cirrhosis with and without ACLF. RESULTS: Urine NGAL was markedly increased in ACLF vs. no ACLF patients (108(35-400) vs. 29(12-73)µg/g creatinine; p<0.001) and was an independent predictive factor of ACLF; the independent association persisted after adjustment for kidney function or exclusion of variables present in ACLF definition. Urine NGAL was also an independent predictive factor of 28day transplant-free mortality together with MELD score and leukocyte count (AUROC 0.88(0.83-0.92)). Urine NGAL improved significantly the accuracy of MELD in predicting prognosis. The LCN2 gene was markedly upregulated in the liver of patients with ACLF. Gene expression correlated directly with serum bilirubin and INR (r=0.79; p<0.001 and r=0.67; p<0.001), MELD (r=0.68; p<0.001) and Interleukin-6 (r=0.65; p<0.001). CONCLUSIONS: NGAL is a biomarker of ACLF and prognosis and correlates with liver failure and systemic inflammation. There is remarkable overexpression of LCN2 gene in the liver in ACLF syndrome. LAY SUMMARY: Urine NGAL is a biomarker of acute-on-chronic liver failure (ACLF). NGAL is a protein that may be expressed in several tissues in response to injury. The protein is filtered by the kidneys due to its small size and can be measured in the urine. Ariza, Graupera and colleagues found in a series of 716 patients with cirrhosis that urine NGAL was markedly increased in patients with ACLF and correlated with prognosis. Moreover, gene coding NGAL was markedly overexpressed in the liver tissue in ACLF.

Renal function at two years in liver transplant patients receiving everolimus: results of a randomized, multicenter study.

In a 24-month prospective, randomized, multicenter, open-label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR) + Reduced tacrolimus (TAC; n = 245), TAC Control (n = 243) or TAC Elimination (n = 231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy-proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR + Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference -2.2%, 97.5% confidence interval [CI] -8.8%, 4.4%). BPAR was less frequent in the EVR + Reduced TAC group (6.1% vs. 13.3% in TAC Control, p = 0.010). Adjusted change in estimated glomerular filtration rate (eGFR) from randomization to month 24 was superior with EVR + Reduced TAC versus TAC Control: difference 6.7 mL/min/1.73 m(2) (97.5% CI 1.9, 11.4 mL/min/1.73 m(2), p = 0.002). Among patients who remained on treatment, mean (SD) eGFR at month 24 was 77.6 (26.5) mL/min/1.73 m(2) in the EVR + Reduced TAC group and 66.1 (19.3) mL/min/1.73 m(2) in the TAC Control group (p < 0.001). Study medication was discontinued due to adverse events in 28.6% of EVR + Reduced TAC and 18.2% of TAC Control patients. Early introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation provided a significant and clinically relevant benefit for renal function at 2 years posttransplant.

Phase I and pharmacokinetic study of IV vinflunine in cancer patients with liver dysfunction.

Vinflunine is a novel tubulin-targeted agent that is currently indicated as a monotherapy in bladder cancer patients. The recommended dose of 320 mg/m(2) is given as an intravenous infusion once every 3 weeks. Vinflunine is metabolized through CYP3A4 and mainly eliminated via the feces. A phase I trial was designed to explore the tolerability and pharmacokinetics of vinflunine in cancer patients with ranging degrees of liver dysfunction (LD). A sequential design was used for patient accrual, with the objective of determining the maximum tolerated dose (MTD) and the recommended dose (RD) of vinflunine in 3 groups of increasing LD levels. Vinflunine and its only active metabolite 4-O-deacetylvinflunine were quantified in serial whole blood samples. PK parameters were derived and compared between LD groups and with a reference PK database. Vinflunine and 4-O-deacetylvinflunine PK parameters were not affected in any of the explored LD levels. Geometric mean values for vinflunine total clearance were 47.8, 37.5 and 45.4 L/h in the 3 groups of increasing degrees of LD, as compared to 42.5 L/h in reference patients with no LD. No relationship was found between vinflunine clearance and the presence or absence of cirrhosis, nor was it found with the presence or absence of liver metastasis or with liver-related biochemical parameters. Based on the observed tolerability profile, the recommended doses of i.v. vinflunine are 320 mg/m(2), 250 mg/m(2) or 200 mg/m(2) for patients with increasing degrees of liver dysfunction.

Efficacy and safety of maribavir dosed at 100 mg orally twice daily for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, double-blind, multicenter controlled trial.

Maribavir is an oral benzimidazole riboside with potent in vitro activity against cytomegalovirus (CMV), including some CMV strains resistant to ganciclovir. In a randomized, double-blind, multicenter trial, the efficacy and safety of prophylactic oral maribavir (100 mg twice daily) for prevention of CMV disease were compared with oral ganciclovir (1000 mg three times daily) in 303 CMV-seronegative liver transplant recipients with CMV-seropositive donors (147 maribavir; 156 ganciclovir). Patients received study drug for up to 14 weeks and were monitored for CMV infection by blood surveillance tests and also for the development of CMV disease. The primary endpoint was Endpoint Committee (EC)-confirmed CMV disease within 6 months of transplantation. In a modified intent-to-treat analysis, the noninferiority of maribavir compared to oral ganciclovir for prevention of CMV disease was not established (12% with maribavir vs. 8% with ganciclovir: event rate difference of 0.041; 95% CI: -0.038, 0.119). Furthermore, significantly fewer ganciclovir patients had EC-confirmed CMV disease or CMV infection by pp65 antigenemia or CMV DNA PCR compared to maribavir patients at both 100 days (20% vs. 60%; p < 0.0001) and at 6 months (53% vs. 72%; p = 0.0053) after transplantation. Graft rejection, patient survival, and non-CMV infections were similar for maribavir and ganciclovir patients. Maribavir was well-tolerated and associated with fewer hematological adverse events than oral ganciclovir. At a dose of 100 mg twice daily, maribavir is safe but not adequate for prevention of CMV disease in liver transplant recipients at high risk for CMV disease.

Everolimus with reduced tacrolimus improves renal function in de novo liver transplant recipients: a randomized controlled trial.

In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30±5 to (i) everolimus initiation with tacrolimus elimination (TAC Elimination) (ii) everolimus initiation with reduced-exposure tacrolimus (EVR+Reduced TAC) or (iii) standard-exposure tacrolimus (TAC Control). Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR). EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss or death at 12 months posttransplantation): 6.7% versus 9.7% (-3.0%; 95% CI -8.7, 2.6%; p<0.001 for noninferiority [12% margin]). tBPAR occurred in 2.9% of EVR+Reduced TAC patients versus 7.0% of TAC Controls (p = 0.035). The change in adjusted estimated GFR from randomization to month 12 was superior with EVR+Reduced TAC versus TAC Control (difference 8.50 mL/min/1.73 m(2) , 97.5% CI 3.74, 13.27 mL/min/1.73 m(2) , p<0.001 for superiority). Drug discontinuation for adverse events occurred in 25.7% of EVR+Reduced TAC and 14.1% of TAC Controls (relative risk 1.82, 95% CI 1.25, 2.66). Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 (95% CI 1.03, 3.00). Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function, compared to a standard tacrolimus exposure regimen 12 months after liver transplantation.

Short- and long-term donor morbidity in right lobe living donor liver transplantation: 91 consecutive cases in a European Center.

The lack of use of a common grading system in reporting morbidity impedes estimation of the true risk to a right lobe living donor (RLLD). We report outcomes in 91 consecutive RLLD's using the validated 5-tier Clavien grading and a quality of life (QOL) questionnaire. The median follow-up was 79 months. The donors were predominantly female (66%), 22 (24%) received autologous blood transfusions. Fifty-three complications occurred in 43 donors (47% morbidity), 19 (37%) were ≥ Grade III, biliary fistula (14%) was the most common. There was no donor mortality. Two intraoperative complications could not be graded and two disfiguring complications in female donors were graded as minor. Two subgroups (first 46 vs. later 45 donors) were compared to study the presence if any, of a learning curve. The later 45 donors had lesser autologous transfusions, lesser rehospitalization and no reoperation and a reduction in the proportion of ≥ Grade III (major) complications (24% vs. 50%; p = 0.06). In the long term, donors expressed an overall sense of well being, but some sequelae of surgery do restrain their current lifestyle. Our results warn against lackadaisical vigilance once RLLD hepatectomy becomes routine.

Reduced-dose tacrolimus with mycophenolate mofetil vs. standard-dose tacrolimus in liver transplantation: a randomized study.

We conducted a multicenter randomized study in liver transplantation to compare standard-dose tacrolimus to reduced-dose tacrolimus with mycophenolate mofetil to reduce the occurrence of tacrolimus side effects. Two primary outcomes (censored criteria) were monitored during 48 weeks post-transplantation: occurrence of renal dysfunction or arterial hypertension or diabetes (evaluating benefit) and occurrence of acute graft rejection (evaluating risk). Interim analyses were performed every 40 patients to stop the study in the case of increased risk of graft rejection. One hundred and ninety-five patients (control: 100; experimental: 95) had been included when the study was stopped. Acute graft rejection occurred in 46 (46%) and 28 (30%) patients in control and experimental groups, respectively (HR = 0.59; 95% CI: [0.37-0.94]; p = 0.024). Renal dysfunction or arterial hypertension or diabetes occurred in 80 (80%) and 61 (64%) patients in control and experimental groups, respectively (HR = 0.68; 95% CI: [0.49-0.95]; p = 0.021). Renal dysfunction occurred in 42 (42%) and 23 (24%) patients in control and experimental groups, respectively (HR = 0.49; 95% CI: [0.29-0.81]; p = 0.004). Leucopoenia (p = 0.001), thrombocytopenia (p = 0.017) and diarrhea (p = 0.002) occurred more frequently in the experimental group. Reduced-dose tacrolimus with mycophenolate mofetil reduces the occurrence of renal dysfunction and the risk of graft rejection. This immunosuppressive regimen could replace full-dose tacrolimus in adult liver transplantation.

Non-invasive ICG-clearance: a useful tool for the management of hepatic artery thrombosis following liver transplantation.

BACKGROUND: The clinical presentation of hepatic artery thrombosis (HAT) post-liver transplantation (LT) varies considerably. Doppler ultrasonography (Doppler US) is the first line investigation, with a diagnostic sensitivity for HAT as high as 92%. Because indocyanine green (ICG) elimination from the blood depends among other factors on the hepatic blood flow, we hypothesized that plasma disappearance rate of indocyanine green (PDR-ICG) can be influenced by the flow in the hepatic artery. Thus, we evaluated the role of PDR-ICG measurement in HAT diagnosis in post-LT patients. PATIENTS AND METHODS: Fourteen liver transplant patients with no visible flow in the hepatic artery (Doppler US) were identified. Of the 14, seven patients had HAT confirmed by CT-angiography. The PDR-ICG measurement, an investigation routinely used in our center, was performed in all 14 patients. RESULTS: The PDR-ICG in patients with HAT was significantly lower than in patients without HAT (5.8 ± 4.3 vs. 23.8 ± 7.4%/min, p= 0.0009). In patients with HAT, after the revascularization, the PDR-ICG value increased (5.8 ± 4.3 vs. 15.6 ± 3.5%/min, p = 0.006). CONCLUSION: The ICG elimination may be an adjunct diagnostic tool in the management of patients with suspected HAT following LT.

Extended measures for controlling an outbreak of VIM-1 producing imipenem-resistant Klebsiella pneumoniae in a liver transplant centre in France, 2003-2004.

We report the successful control of an outbreak caused by imipenem-resistant VIM-1-producing Klebsiella pneumoniae (IR-Kp) in France. This outbreak occurred in a care centre for abdominal surgery that includes a 15-bed liver intensive care unit and performs more than 130 liver transplantations per year. The index case was a patient with acute liver failure transferred from a hospital in Greece for urgent liver transplantation who was carrying IR-Kp at admission as revealed by routine culture of a rectal swab. Infection control measures were undertaken and included contact isolation and promotion of hand hygiene with alcohol-based hand rub solution. Nevertheless, secondary IR-Kp cases were identified during the six following months from 3 December 2003 to 2 June 2004. From 2 June to 21 October, extended infection control measures were set up, such as cohorting IR-Kp carriers, contact patients and new patients in distinct sections with dedicated staff, limiting ward admission, and strict control of patient transfer. They led to a rapid control of the outbreak. The global attack rate of the IR-Kp outbreak was 2.5%, 13% in liver transplant patients and 0.4% in the other patients in the care centre (p<0.005). Systematic screening for IR-Kp of all patients admitted to the care centre is still maintained to date and no secondary IR-Kp case has been detected since 2 June 2004.

Management of liver failure in general intensive care unit.

OBJECTIVE: To produce French guidelines on Management of Liver failure in general Intensive Care Unit (ICU). DESIGN: A consensus committee of 23 experts from the French Society of Anesthesiology and Critical Care Medicine (Société française d'anesthésie et de réanimation, SFAR) and the French Association for the Study of the Liver (Association française pour l'étude du foie, AFEF) was convened. A formal conflict-of-interest (COI) policy was developed at the start of the process and enforced throughout. The entire guideline process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide their assessment of the quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. Some recommendations were ungraded. METHODS: Two fields were defined: acute liver failure (ALF) and cirrhotic patients in general ICU. The panel focused on three questions with respect to ALF: (1) Which etiological examinations should be performed to reduce morbidity and mortality? (2) Which specific treatments should be initiated rapidly to reduce morbidity and mortality? (3) Which symptomatic treatment should be initiated rapidly to reduce morbidity and mortality? Seven questions concerning cirrhotic patients were addressed: (1) Which criteria should be used to guide ICU admission of cirrhotic patients in order to improve their prognosis? (2) Which specific management of kidney injury should be implemented to reduce morbidity and mortality in cirrhotic ICU patients? (3) Which specific measures to manage sepsis in order to reduce morbidity and mortality in cirrhotic ICU patients? (4) In which circumstances, human serum albumin should be administered to reduce morbidity and mortality in cirrhotic ICU patients? (5) How should digestive haemorrhage be treated in order to reduce morbidity and mortality in cirrhotic ICU patients? (6) How should haemostasis be managed in order to reduce morbidity and mortality in cirrhotic ICU patients? And (7) When should advice be obtained from an expert centre in order to reduce morbidity and mortality in cirrhotic ICU patients? Population, intervention, comparison and outcome (PICO) issues were reviewed and updated as required, and evidence profiles were generated. An analysis of the literature and recommendations was then performed in accordance with the GRADE® methodology. RESULTS: The SFAR/AFEF Guidelines panel produced 18 statements on liver failure in general ICU. After two rounds of debate and various amendments, a strong agreement was reached on 100% of the recommendations: six had a high level of evidence (Grade 1 ±), seven had a low level of evidence (Grade 2 ±) and six were expert judgments. Finally, no recommendation was provided with respect to one question. CONCLUSIONS: Substantial agreement exists among experts regarding numerous strong recommendations on the optimum care of patients with liver failure in general ICU.

Real-time PCR on the first galactomannan-positive serum sample for diagnosing invasive aspergillosis in liver transplant recipients.

Invasive aspergillosis (IA) is a life-threatening complication of liver transplantation. Detection of circulating galactomannan (GM) in serum samples is a method to improve the microbiological diagnosis in patients at risk for IA. However, the assay is hampered by false-positive results. The search for circulating Aspergillus DNA in the first GM-positive sample could improve the specificity of the test. Among 484 liver transplant recipients followed in a single center over 4 years, 25 patients had at least 1 GM-positive serum sample. The threshold of GM positivity was a ratio >or=1. These 25 patients were classified by the clinicians as probable IA (n=11), possible IA (n=2), and no IA (n=12) using the EORTC/MSG criteria with blinding to the polymerase chain reaction (PCR) results. After 1 mL aliquots of the first GM-positive serum sample were thawed, 2 independent DNA extractions were performed using the MagNA Pure Compact apparatus. Real-time amplification targeted at Aspergillus fumigatus mitochondrial DNA was performed on 10 microL of the final eluate in duplicate in the 2 independent DNA extractions using a LightCycler instrument. A sample was considered positive when the crossing point was

Pathophysiology and therapy of irinotecan-induced delayed-onset diarrhea in patients with advanced colorectal cancer: a prospective assessment.

PURPOSE: Irinotecan (CPT-11), a camptothecin derivative, has shown efficacy against colorectal cancer. Delayed-onset diarrhea is its main limiting toxicity. The aim of this study was to determine the pathophysiology of CPT-11-induced delayed-onset diarrhea and assess the efficacy of combined antidiarrheal medication in a phase II, prospective, successive-cohorts, open study. PATIENTS AND METHODS: Twenty-eight patients with advanced colorectal cancer refractory to fluorouracil (5-FU) therapy received CPT-11 350 mg/m2 every 3 weeks. The first cohort of 14 consecutive patients explored for the mechanism of diarrhea received acetorphan (a new enkephalinase inhibitor) 100 mg three times daily; the second 14-patient cohort received, in addition to acetorphan, loperamide 4 mg three times daily. Before treatment, and if late diarrhea occurred, patients underwent colon mucosal biopsies for CPT-11 and topoisomerase I levels; intestinal transit time; fecalogram; fat and protein excretion; alpha1-antitrypsin clearance; D-xylose test; blood levels for vasoactive intestinal polypeptide, glucagon, gastrin, somatostatin, prostaglandin E2, and carboxylesterase; CPT-11/SN-38 and SN-38 glucuronide pharmacokinetics; and stool cultures. RESULTS: Delayed-onset diarrhea occurred during the first three treatment cycles in 23 patients (82%). Electrolyte fecal measurements showed a negative or small osmotic gap in nine of nine patients and an increased alpha1-antitrypsin clearance in six of six patients. There were no modifications in stool cultures or hormonal dysfunction. Four of 11 patients (36%) with delayed-onset diarrhea in the first cohort responded to acetorphan, whereas nine of 10 patients (90%) responded to the combination of acetorphan and loperamide (P < .02). CONCLUSION: CPT-11-induced delayed-onset diarrhea is caused by a secretory mechanism with an exudative component. Early combined treatment with loperamide and acetorphan seems effective in controlling the diarrheal episodes.

Artificial liver support: a real step forward.

Since the early 1960s, several authors reported on the use of some experimental artificial liver devices in order to support patients with either acute liver failure (ALF) or end-stage chronic liver disease. In the 1980s, liver transplantation became an established real treatment replacing the whole liver with a major survival benefit. In the 1990s, the concept of albumin dialysis appeared as a new revolution in the concept of dialysis with the great capacity of removal of toxins, drugs and molecules strongly bound to albumin. Currently, three artificial liver support devices are available: The MARS®, the Prometheus® and the SPAD®. The most widely studied and used system is the MARS® that uses albumin dialysis to replace the detoxification function of the liver. MARS has shown in several uncontrolled studies and few randomized studies an improvement in the patient condition in terms of clinical symptoms (hepatic encephalopathy, pruritus, jaundice) and in liver and kidney biological parameters bringing these patients safely to liver transplantation. MARS® has shown for some patients with ALF (mainly paracetamol intoxication) an improvement of spontaneous or transplant free survival. The use of MARS in acute on chronic liver failure (ACLF) require further studies based on strict definition of the syndrome. The use of albumin dialysis technique, require the performance of multiple sessions of treatment or even (in situations of ALF) a continuous treatment in order to improve spontaneous recovery or bridge these patients to liver transplantation. The performance of these systems would need further improvement. Large randomized trials are still needed in both patients with ALF and ACLF to establish the indications, the timing and the real place of liver support therapies. Meanwhile, early use of these devices in patients with ALF and ACLF could be considered as an additional tool among others in the management of these patients in specialized liver units.

The use of ABO-incompatible grafts in liver transplantation: a life-saving procedure in highly selected patients.

The aim of this study was to assess the long term results of 43 ABO-incompatible liver transplantations performed in 40 patients. The 5-year patient and graft survival rates were 50 and 20%, respectively. In the group of patients transplanted in emergency for fulminant or subfulminant liver failure, ABO incompatibility had no significant impact on patient survival (P = 0.09). Graft survival, however, was significantly impaired (P = 0.0002) through a greater incidence of hyperacute rejection (20%), vascular thrombosis, and biliary injury (56%). Increasing the magnitude of immunosuppression and postoperatively reducing the titer of anti A/B antibodies by plasmapheresis had little influence on the incidence of these complications and were associated with a greater incidence of septic complications. These results indicate that the use of ABO-incompatible liver grafts is a life-saving procedure in patients with life-threatening acute liver failure, but at a high price. Justification for accepting or not accepting an ABO-incompatible graft in these emergency situations depends on the personal choice in giving priority to saving the patient in an acute life-threatening condition or to giving the graft the best chance of success. To avoid this difficult choice, efforts should aim at expanding the pool of grafts available in emergency, at developing artificial support devices that could allow to safely delay transplantation, or at more efficiently controlling the humoral response.

Pulsed field gel electrophoresis typing of coagulase-negative staphylococci with decreased susceptibility to teicoplanin isolated from an intensive care unit.

Increased isolation of coagulase-negative staphylococci (CoNS) with decreased susceptibility to teicoplanin prompted this epidemiological survey in the authors intensive care unit. Of 224 medical and surgical patients with hepatobiliary disease, in hospital between December 1998 and July 1999, 14 (6.3%) had at least one isolate of CoNS with decreased susceptibility to teicoplanin. A total of 27 isolates with decreased susceptibility to teicoplanin were recovered from these 14 patients. Pulsed field electrophoresis (PFGE) with Sma I endonuclease demonstrated that CoNS isolates obtained from different patients were unrelated. In addition, different isolates obtain from the same patient were also unrelated, with the exception of two patients. Eighteen out of 27 isolates (66.7%) with decreased susceptibility to teicoplanin were recovered after an earlier treatment with teicoplanin or vancomycin (median 13.1 g, range 2.4-32.7 g per patient). Only four CoNS strains with decreased susceptibility to teicoplanin induced serious infection, all of which responded well to vancomycin therapy. Emergence of CoNS strains with decreased susceptibility to teicoplanin remained limited in hospitalized patients, and was not related to a clonal spread of a particular resistant strain.

[Labor complications of the HELLP syndrome without any predictive factors]. / Accouchement compliqué de HELLP syndrome sans facteur prédictif de survenue. Deux observations.

Liver disease is a rare complication of pregnancy which can be serious for both the mother and the infant. In particular, HELLP syndrome (hemolysis, elevated liver enzymes and a low platelet count) is a life threatening complication of severe preeclampsia. Pregnancies complicated by the HELLP syndrome are usually associated with increased maternal and perinatal morbidity and mortality including disseminated intravascular coagulopathy, pulmonary and cerebral oedema, acute renal failure, rupture of the liver hematoma and a variety of hemorrhagic complications. The HELLP syndrome occurs in 4 to 12% of patients with severe preeclampsia and prompt delivery is the only treatment. We report two cases of HELLP syndrome which developed in women during delivery and without any predictive factors during pregnancy.