[Show abstract][Hide abstract] ABSTRACT: Donor-recipient match is a matter of debate in liver transplantation. D-MELD (donor age × recipient biochemical model for end-stage liver disease [MELD]) and other factors were analyzed on a national Italian database recording 5946 liver transplants. Primary endpoint was to determine factors predictive of 3-year patient survival. D-MELD cutoff predictive of 5-year patient survival <50% (5yrsPS<50%) was investigated. A prognosis calculator was implemented (http://www.D-MELD.com). Differences among D-MELD deciles allowed their regrouping into three D-MELD classes (A < 338, B 338-1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95% confidence interval [CI], 1.44-2.85) in D-MELD class C versus B. The OR was 0.40 (95% CI, 0.24-0.66) in class A versus class B. Other predictors were hepatitis C virus (HCV; OR = 1.42; 95% CI, 1.11-1.81), hepatitis B virus (HBV; OR = 0.69; 95% CI, 0.51-0.93), retransplant (OR = 1.82; 95% CI, 1.16-2.87) and low-volume center (OR = 1.48; 95% CI, 1.11-1.99). Cox regressions up to 90 months confirmed results. The hazard ratio was 1.97 (95% CI, 1.59-2.43) for D-MELD class C versus class B and 0.42 (95% CI, 0.29-0.60) for D-MELD class A versus class B. Recipient age, HCV, HBV and retransplant were also significant. The 5yrsPS<50% cutoff was identified only in HCV patients (D-MELD ≥ 1750). The innovative approach offered by D-MELD and covariates is helpful in predicting outcome after liver transplantation, especially in HCV recipients.
American Journal of Transplantation 12/2011; 11(12):2724-2736. · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Liver dysfunction is an important cause of morbidity and mortality after orthotopic liver transplantation (OLT). The Molecular Adsorbent Recirculating System (MARS) is an albumin-based dialysis system designed to enhance the excretory function of a failing liver. MARS has been successfully used in patients affected by advanced liver disease and presenting with severe cholestasis. The aim of this study was to evaluate the safety and clinical efficacy of MARS in patients with liver dysfunction after OLT. Seven patients (primary nonfunction, 2 patients; graft dysfunction, 5 patients) fulfilled the inclusion criteria of serum bilirubin level >15 mg/dL and least 1 of the following clinical signs: hepatic encephalopathy (HE) > or = grade II, hepatorenal syndrome (HRS), and intractable pruritus. Graft and patient survival rates at 6 months were 42.8% and 57.1%, respectively. All patients tolerated MARS treatment, with no adverse event. In all patients, a decrease in serum bilirubin (P < .05), bile acids (P < .05), serum creatinine, and ammonia levels was observed after treatment with MARS. A considerable improvement of HE, as well as renal and synthetic liver functions, was observed in 4 of 5 patients with graft dysfunction, but not among those with primary nonfunction. The patients with intractable pruritus showed significant improvement of this symptom after MARS therapy. Thus, MARS is a safe, therapeutic option for the treatment of liver dysfunction after OLT. Further studies are necessary to confirm whether this treatment is able to improve both graft and patient survival.
[Show abstract][Hide abstract] ABSTRACT: Determination of cardiac output (CO) is crucial for perioperative monitoring of orthotopic liver transplant (OLT) recipients. A pulmonary artery catheter (PAC) has always been considered the "gold standard" of hemodynamic monitoring. The aim of this study was to evaluate the suitability of a transesophageal echo-Doppler device (ED) as a minimally invasive device to measure CO in OLT. ED was compared with the standard PAC technique taking into account the disease severity of OLT recipients as defined by the model for end-stage liver disease (MELD) score. We enrolled 42 cirrhotic patients scheduled for OLT 3 thermodilution CO measurements were taken by a PAC and the most recent ED measurement (CO(ED)) was also recorded. Paired measurements of CO were performed at standard times, unless there were additional clinical needs. Recipients were stratified into 3 groups according to MELD score: MELD score < or = 15 (14 patients); MELD score between 16 and 28 (17 patients); and MELD score > or = 29 (11 patients). We performed 495 paired measurements of CO. Mean bias was 0.34 +/- 0.9 L/min and limits of agreement were -1.46 and 2.14 L/min. In patients with MELD score <15, the bias was 0.12 +/- 0.55. The ED results were not interchangeable with PAC, because of the large limits of agreement. However, in cirrhotic patients with MELD scores <15, the precision of the new method was similar to that of PAC; therefore, in this subset of patients, it may represent a reliable alternative to PAC.
[Show abstract][Hide abstract] ABSTRACT: Corticosteroids may improve haemodynamics and facilitate weaning from catecholamines in septic shock. According to some authors, such effects are only accomplished in the presence of absolute or relative adrenal insufficiency. Consequently, corticosteroids are usually given only to patients that present low blood cortisol values or show an inadequate response to cosyntropin (Synachten test). We report the case of a woman affected by septic shock secondary to pneumonia and dependent on norepinephrine infusion for 26 days, who was weaned from catecholamines with hydrocortisone, 100 mg/day i.v. She exhibited a normal response to Synachten, but corticosteroid therapy was continued because haemodynamics improved promptly. A pharmacological effect was hypothesized; the contemporary increase of platelet, decrease of white blood cells, and decrease of plasma fibrinogen supported this hypothesis.
[Show abstract][Hide abstract] ABSTRACT: Here we report a case of leptospirosis without fever during the late stage of pregnancy in which the initial clinical presentation was more suggestive of a pregnancy-related liver dysfunction rather than an infectious disease. A 32-year-old primipara at 37 week of gestation was hospitalised with a 10-day history of nausea, vomiting, and abdominal pain without fever. Initial routine blood tests showed hyperbilirubinemia, a moderate increase in transaminase levels, severe coagulopathy and an increased creatinine level. On clinical suspicion of pregnancy-related liver dysfunction such as HELLP syndrome (hemolysis, elevated liver enzyme levels, low platelet count) or acute fatty liver of pregnancy (AFLP), emergency caesarean section was performed and a healthy baby was delivered. Postoperatively, the patient was stable, but 5 days later she developed clouding of consciousness, severe jaundice and respiratory failure. At this time, an infectious disease was considered and leptospirosis was confirmed by serological tests. In conjunction with intensive care management, antibiotic therapy was given; the patient was discharged in good condition and her baby did not develop signs of active leptospirosis. While leptospirosis is rare in pregnancy, this is the first report of acute infection without fever mimicking the clinical pattern of HELLP syndrome or AFLP
[Show abstract][Hide abstract] ABSTRACT: We assessed the safety and clinical efficacy of the Molecular Adsorbent Recirculating System (MARS) in liver failure patients admitted to our intensive care unit (ICU) from May 2000 to February 2006. Of 28 adult patients with bilirubin >15 mg/dL and hepatic encephalopathy (HE) grade > or =2 or hepato-renal syndrome, 22 patients were included in the study, because 6 patients were older than 65 years of age or showed recent alcohol abuse or extrahepatic malignancy. Patients were assigned to 2 groups according to whether MARS therapy was associated with a transplantation procedure: 11 patients received MARS therapy and liver transplantation (OLT group) and 11 patients received MARS therapy alone (non-OLT group). Five of 11 patients in the OLT group were listed for transplantation and 6 patients with graft failure for retransplantation. The patients in the OLT and non-OLT groups were similar in MELD, SOFA, and SAPS scores. All patients were stable and free from complications. MARS significantly reduced bilirubin, bile acids, and blood urea nitrogen (BUN) levels in both groups (P < .05), whereas a significant decrease in ammonia level was observed in the OLT group. Patient survival rates at 3 and 6 months in the OLT group were 91% and 73%, respectively, and in the non-OLT group, 9% and 9%, respectively (P < .001). MARS was safe and well tolerated, improving biochemical parameters, neurological function, and pruritus. In terms of survival, the use of MARS alone was not effective due to the high rate of multiple organ failure. Nevertheless, the association of MARS with a transplant/retransplantation procedure was highly effective.
[Show abstract][Hide abstract] ABSTRACT: Italian Poison Centers answer to approximately 100,000 calls per year. Potentially, this activity is a huge source of data for toxicovigilance and for syndromic surveillance. During the last decade, surveillance systems for early detection of outbreaks have drawn the attention of public health institutions due to the threat of terrorism and high-profile disease outbreaks. Poisoning surveillance needs the ongoing, systematic collection, analysis, interpretation, and dissemination of harmonised data about poisonings from all Poison Centers for use in public health action to reduce morbidity and mortality and to improve health. The entity-relationship model for a Poison Center relational database is extremely complex and not studied in detail. For this reason, not harmonised data collection happens among Italian Poison Centers. Entities are recognizable concepts, either concrete or abstract, such as patients and poisons, or events which have relevance to the database, such as calls. Connectivity and cardinality of relationships are complex as well. A one-to-many relationship exist between calls and patients: for one instance of entity calls, there are zero, one, or many instances of entity patients. At the same time, a one-to-many relationship exist between patients and poisons: for one instance of entity patients, there are zero, one, or many instances of entity poisons. This paper shows a relational model for a poison center database which allows the harmonised data collection of poison centers calls.
[Show abstract][Hide abstract] ABSTRACT: Molecular adsorbent recycling system (MARS) treatment is able to remove both hydrosoluble and small- and medium-sized lipophilic toxins. MARS plays an important role in modifying liver failure complications, such as hepatorenal syndrome and hepatic encephalopathy. We sought to evaluate the clinical efficacy and safety of a MARS device in a consecutive series of hepatic failure patients.
Twenty patients with acute liver failure, transplantation failure, or acute on chronic liver failure fulfilled the inclusion criteria of total bilirubin > or =10 mg/dL and at least one of the following: hepatic encephalopathy (HE) > or =II grade, hepatorenal syndrome (HRS) for chronic patients or total bilirubin > or =5 mg/dL and HE > or =I grade for acute patients.
MARS was able to reduce cholestatic parameters and improve neurologic status and renal function parameters in all treated patients. We also observed an improvement in the 3-month survival rate compared to the expected outcome in patients with MELD scores between 20 and 29, as well as 30 and 39.
Based on these results, we confirm the safety and clinical efficacy of MARS treatment, with the best results in patients with MELD score of 20 to 29. Further studies are necessary to confirm whether this treatment is able to modify patient outcomes and prognosis.
[Show abstract][Hide abstract] ABSTRACT: Oxidative injury occurs as a direct result of hepatitis C virus (HCV) core protein expression both in vitro and in vivo, and may be due to a direct effect on mitochondria. The ketoisocaproic acid (KICA) breath test is a simple, reliable, and noninvasive test to evaluate hepatic mitochondrial function. Albumin dialysis (MARS) is an effective bridge treatment for patients with acute failure superimposed on chronic liver disease. The aim of our study was to evaluate the improvement of mitochondrial function measured by KICA in patients undergoing MARS for acute-on-chronic HCV liver failure.
Five patients with HCV chronic infection undergoing MARS treatment for acute decompensation were enrolled. Before and after each MARS treatment, patients underwent blood testing for the main hematochemical parameters as well as for mitochondrial function by the KICA breath test and the arterial ketone bodies ratio (AKBR).
MARS treatment effectively decreased the serum level of total bilirubin, bile acids, urea, and ammonium. Moreover, MARS treatment produced an increase in AKBR and in the cumulative percentage of (13)CO(2) recovered in exhaled air 2 hours after KICA ingestion.
Liver mitochondrial function appears to be beneficially affected by MARS treatment.
[Show abstract][Hide abstract] ABSTRACT: The clearance of plasma cytokines by means of albumin dialysis (MARS) has been demonstrated in various studies involving patients affected by either acute liver failure (ALF) or acute on chronic liver failure. The aim of the study was to measure the plasma levels of TNF-alpha, IL-6, and IL-1beta in patients with ALF after each MARS treatment to evaluate the relationship between variations in cytokines levels and patient prognosis.
Ten patients with ALF undergoing several MARS treatments were enrolled (group 1). Blood samples were collected before and after each MARS treatment to measure TNF-alpha, IL-6, and IL-1beta, and other hematochemical parameters. We also enrolled 10 patients with ALF who underwent standard therapy (group 2) as well as a control group of 10 healthy subjects matched for sex and age (group 3).
MARS reduced total bilirubin levels, biliary acids, BUN, ammonia, TNF-alpha, IL-6, and IL-1beta (P < .05). Moreover, the reduction in inflammatory cytokines levels and improved prognosis were related.
We confirmed the therapeutic efficacy of MARS treatment for ALF, which appeared to be related to removal of toxins and inflammatory cytokines determine that which patients prognosis.
[Show abstract][Hide abstract] ABSTRACT: In order to compare two mathematical methods to assess the blood CO2 equilibration curve from a single blood gas analysis [Loeppky, J.A., Luft, U.C., Fletcher, E.R., 1983. Quantitative description of whole blood CO2 dissociation curve and Haldane effect. Resp. Physiol. 51, 167-181; Giovannini, I., Chiarla, C., Boldrini, G., Castagneto, M., 1993. Calculation of venoarterial CO2 concentration difference. J. Appl. Physiol. 74, 959-964], arterial and central venous blood gas analyses and oximetry were performed before and after ventilatory resetting, at constant arterial O2 saturation, in 12 mechanically ventilated patients. CO2 equilibration curves obtained from basal arterial blood gas analyses were used to predict arterial CO2 content after ventilatory resetting and vice versa. Internal consistency was very good for both methods and comparable. Method 2 also yielded excellent predictions of changes of arterial pH associated with ventilatory resetting. In determining Haldane effect, method 2 yielded very stable results within the expected range of values, while method 1 yielded a wider spread of results. Method 2 appeared more suitable to determine the Haldane effect in the conditions of the study, probably due to an approach minimizing the effect of potential sources of inaccuracy.
[Show abstract][Hide abstract] ABSTRACT: The outcome of liver transplantation (LTx) has been correlated with several donor and recipient factors.
A database of 191 consecutive LTx cases was analyzed using Kaplan-Meier and Cox regression statistics based on 80 variables. To avoid additional effects of late events on patient survival, the chosen endpoint was 6 months. Data were evaluated using SPSS statistical software.
Kaplan-Meier analysis revealed a difference in 1- to 6-month graft survival between patients transplanted with organs from donors older versus younger than 60 years (Breslow, P <.01). Differences in 1- to 6-month graft survivals were observed between patients listed as UNOS status 3, 2B, 2A, and 1: the outcomes for UNOS status 2B versus UNOS status 2A and UNOS status 2B versus status 1 were significant (P <.05). Differences in 1- to 6-month graft survival rates were found between patients with versus without sepsis (P <.05), and with versus without rejection episodes (P <.01). Cox regression analysis revealed only three of the variables to be independent prognostic predictors of graft failure: donor age; postoperative septic status; and rejection. The best mathematical multivariate Cox regression model linked donor age + donor Na + rejection + sepsis to 1- to 6-month graft survival (chi-square = 29.06, P <.001).
Factors predictive of 1- to 6-month graft survival after liver transplantation include donor age; UNOS status; sepsis; and rejection.