Plasma proteome to look for diagnostic biomarkers of early bacterial sepsis after liver transplantation: a preliminary study.

BACKGROUND: While outcome continuously improves after liver transplantation, sepsis remains the leading cause of early postoperative mortality. Diagnosis of infections remains particularly difficult in these patients. This study used plasma profiling coupling Proteinchip array with surface-enhanced laser desorption ionization time-of-fly mass spectrometry to search for biomarkers of postoperative sepsis in patients who underwent liver transplantation. METHODS: Diagnosis of sepsis at day 5 relied on widely accepted clinical signs and positive culture of microbiologic samples. Profiles of day 5 plasma were obtained from SELDI-TOF CM10 chip (BioRad, Marnes-la-Coquette, France) analysis. Mean peak intensity of proteins was compared between septic and nonseptic plasma by U test followed by analysis of the area under the receiver-operating characteristic for the significant peaks. Diagnostic performance of significant proteins was established in a derivation set and in a validation set. RESULTS: In the derivation set of 31 patients with and 30 without infection, 23 plasma protein peaks were differentially expressed between patients with and without sepsis. Combination of five peaks allowed sepsis diagnosis with a positive likelihood ratio of 12.5 and a C-statistics of 0.72, 95% CI 0.57-0.85. In the validation set of 31 patients with infection and 34 without infection, the five peaks were differentially expressed as well and allowed day 5 sepsis diagnosis with a positive likelihood ratio of 5.1 and C-statistics of 0.74 (0.58-0.85). CONCLUSION: A combination of five plasma protein peaks may provide material for useful diagnostic biomarkers of postoperative sepsis in patients undergoing liver transplantation. However, these proteins remain to be identified.

Prospective validation of the "fifty-fifty" criteria as an early and accurate predictor of death after liver resection in intensive care unit patients.

BACKGROUND: Postoperative liver failure after hepatectomy has been identified by the association of prothrombin time <50% and serum bilirubin >50 micromol/L (the "50-50" criteria). Whether these criteria are of prognostic value in a prospective study remains unknown. OBJECTIVE: To determine prospectively the prognostic value of the 50-50 criteria on day 3 and day 5 in intensive care unit (ICU) patients after hepatectomy. METHODS: From January 2005 to February 2007, among 436 elective liver resections, 99 (23%) consecutive patients aged 58 +/- 17 years were admitted postoperatively in ICU with a mean SAPSII 25 +/- 10. Malignant disease was present in 87 and major resections (< or =3 segments) were performed in 79 (80%) cases. The underlying liver parenchyma was abnormal in 59 (59%) cases including cirrhosis, fibrosis, or steatosis >30% in 19, 23, and 17 patients, respectively. RESULTS: The 50-50 criteria were present on day 3 in 10 patients and on day 5 in 13. Ten patients (10, 6%) died in ICU. Survivors with these criteria were characterized by early aggressive support including reoperation and/or liver assist system. Nonsurvivors were more often cirrhotic, had significantly higher SAPS II and more frequently postoperative prolonged mechanical ventilation. The 50-50 criteria on days 3 and 5 were predictors of death on multivariate analysis [OR (95% CI): 12.7 (2.3-71.4), OR (95% CI): 29.4 (4.9-167), respectively]. CONCLUSIONS: After hepatic resection, results of this prospective study validate the 50-50 criteria as a predictive factor of mortality in ICU on both days 3 and 5. These criteria allow an early diagnosis of postoperative liver failure, which may contribute to reduce mortality in ICU patients after hepatectomy.

Respiratory complications: a major concern after right hepatectomy in living liver donors.

BACKGROUND: One of the main concerns after living donor liver transplantation is the risk of morbidity and/or mortality that it imposes on the donors. Respiratory postoperative complications in living liver donors have already been reported but their frequency seems to be underestimated. We designed a prospective study to evaluate the rate and the nature of postoperative pulmonary complications in 112 consecutive donors. METHODS: The medical records of the 112 living liver donors operated on at our center from 1998 to 2003 were reviewed and all the cases of respiratory complications were retrieved. Moreover, since 2000, all patients had a computed tomography angiography of the thorax at day 7 on a prospective basis. RESULTS: In all, 112 hepatectomies (44 right and 68 left) for adult-to-adult or adult-to-child liver donation were performed in our center. No postoperative mortality was recorded. Fourteen major respiratory complications developed in of 11 of 112 donors (9.8%), in all cases after right hepatectomy, and included nonsevere pulmonary embolism (n=7), right pleural empyema (n=3), and bacterial pneumonia (n=3). Minor respiratory complications (7.1% of the donors) included iatrogenic pneumothorax (n=3) and pleural effusion requiring thoracocentesis (n=5). Abdominal complications (mainly biliary leak) developed in 10 donors (8.9%), who in the vast majority remained free of pulmonary complications. CONCLUSIONS: In our series, pulmonary complications are frequent in living liver donors. These complications are mainly observed after right hepatectomy. The particular prevalence of pulmonary embolism should lead to focus on its early diagnosis and prevention.

Prognostic Value of Preoperative Brain Natriuretic Peptide Serum Levels in Liver Transplantation.

BACKGROUND: Brain natriuretic peptide (BNP) serum concentration has been shown to be a preoperative predictor of postoperative outcome in high risk surgery. Whether it is able to predict early post-liver transplantation (LT) mortality in cirrhotic patients is unanswered. METHODS: Prospective monocenter observational study including all consecutive patients who received LT for cirrhosis and for whom a preoperative BNP serum dosage was available between January 2011 and December 2014. RESULTS: During the period, 207 cirrhotic patients among 525 LT were studied. The ICU and 180-day mortality rates were, respectively, 6% and 8%. Pre-LT BNP concentration, adjusted on model of end-stage liver disease (MELD) score, was an independent factor of ICU and 180-day mortality rates (for each 50 pg/mL increase; hazard ratio, 1035 [1.022-1.049]; P < 0.001 and 1.035 [1.014-1057]; P = 0.001). According to the receiver operator characteristic curve with an accuracy of 0.79 (0.66-0.93), the optimal cutoff value of pre-LT BNP serum level to predict ICU mortality was 155 pg/mL with a negative predictive value of 99%. All patients with MELD score exceeding 25 and pre-LT serum BNP level less than 155 pg/mL survived, whereas patients combining MELD score exceeding 25 and pre-LT BNP concentration exceeding 155 pg/mL had a 27% ICU mortality rate (P = 0.03). CONCLUSIONS: In cirrhotic patients, pre-LT BNP serum level was an independent predictor of post-LT ICU mortality. With its excellent negative predictive value, the use of this biomarker in combination with MELD score could be useful to better predict post-LT early outcome.

The "50-50 criteria" on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy.

OBJECTIVE: To standardize the definition of postoperative liver failure (PLF) for prediction of early mortality after hepatectomy. SUMMARY BACKGROUND DATA: The definition of PLF is not standardized, making the comparison of innovations in surgical techniques and the timely use of specific therapeutic interventions complex. METHODS: Between 1998 and 2002, 775 elective liver resections, including 69% for malignancies and 60% major resections, were included in a prospective database. The nontumorous liver was abnormal in 43% with steatosis >30% in 14%, noncirrhotic fibrosis in 43%, and cirrhosis in 12%. The impact of prothrombin time (PT) <50% and serum bilirubin (SB) >50 micromol/L on postoperative days (POD) 1, 3, 5, and 7 was analyzed. RESULTS: The lowest PT level was observed on postoperative day (POD) 1, while the peak of SB was observed on POD 3. These 2 variables tended to return to preoperative values by POD 5. The median interval between hepatectomy and postoperative death was 15 days (range, 5-39 days). Postoperative mortality significantly increased in patients with PT <50% and SB >50 microml/L. The conjunction of PT <50% and SB >50 micromol/L on POD 5 was a strong predictive factor of mortality. In patients with significant morbidity, this "50-50 criteria" was met 3 to 8 days before clinical evidence of complications. CONCLUSIONS: The association of PT <50% and SB >50 microml/L on POD 5 (the 50-50 criteria) was a simple, early, and accurate predictor of more than 50% mortality rate after hepatectomy. This criteria could be identified early enough, before clinical evidence of complications, for specific interventions to be applied in due time.

Prevalence, molecular epidemiology, and clinical significance of heterogeneous glycopeptide-intermediate Staphylococcus aureus in liver transplant recipients.

We investigated the prevalence, molecular epidemiology, and clinical significance of heterogeneous glycopeptide-intermediate Staphylococcus aureus (hGISA) isolates in 48 liver transplant recipients infected or colonized with methicillin-resistant S. aureus over a 5-year period. Strains were screened for hGISA on Mueller-Hinton agar containing 5 mg of teicoplanin per liter. Heterogeneous glycopeptide resistance was confirmed by the E-test method with a dense inoculum and a simplified method of population analysis. hGISA strains were found in 13 (27%) of the 48 patients studied. Eleven of the 13 strains shared a common multiresistant phenotype with homogeneous methicillin resistance and gentamicin resistance, and they were closely related according to the results of pulsed-field gel electrophoresis. Only 2 of the 13 patients infected or colonized with hGISA strains had previously received glycopeptide therapy. Most patients were successfully treated with vancomycin, but one patient who failed to respond to vancomycin subsequently died. These results suggest that the high prevalence of hGISA among our patients was due to the clonal spread of a multiresistant strain.